WO2022099093A1

WO2022099093A1 - Scaffolds for enhancing neutrophils and uses thereof

Info

Publication number: WO2022099093A1
Application number: PCT/US2021/058359
Authority: WO
Inventors: Nisarg J. SHAH; Matthew D. KERR; David J. Mooney
Original assignee: President And Fellows Of Harvard College; The Regents Of The University Of California
Priority date: 2020-11-06
Filing date: 2021-11-05
Publication date: 2022-05-12
Also published as: WO2022099093A8

Abstract

The present invention provides compositions and methods that enhance neutrophil recovery in a subject and/or that provide for delivery of therapeutic agents.

Description

SCAFFOLDS FOR ENHANCING NEUTROPHILS AND USES THEREOF RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No.63/110,528, filed November 6, 2020, the entire contents of which is hereby incorporated herein by reference. GOVERNMENT SUPPORT This invention was made with U.S. Government support under AR073761, AR064194, and CA153915 awarded by the National Institutes of Health. The Government has certain rights in the invention. BACKGROUND OF THE INVENTION Neutrophils mediate essential host defense against pathogens and are among the earliest responders in tissue injury^1-3. Neutrophil deficiency, termed neutropenia, contributes to opportunistic infections and could impair tissue regeneration in affected individuals ^4-7. In autologous hematopoietic stem cell transplantation (HSCT) pre-conditioning myelosuppressive regimens can contribute to a marked transient post-therapy impairment of neutrophils and render recipients susceptible to immune deficiency-associated complications for up to several weeks ^{6, 8-11}. Post-HSCT neutrophil regeneration follows successful bone marrow engraftment of transplanted hematopoietic cells ^{12, 13}, facilitated by granulocyte colony stimulating factor (G- CSF)-mediated granulopoiesis of hematopoietic cells ^14-16. Neutropenia is typically treated as an emergency and, in a subset of patients, the risk of neutropenia may be prophylactically addressed with post-HSCT subcutaneous injection of recombinant human G-CSF (filgrastim) to facilitate recovery ^{6, 14, 17, 18}. Daily injections are used as G-CSF has a half-life of a 3 – 4 hours, which can be extended by conjugating G-CSF with polyethylene glycol (PEGylation) 19, 20. However, immune responses against PEG have been demonstrated to enhance clearance of PEG-G-CSF in an antibody-dependent manner²¹. As multiple cycles of PEG-G-CSF treatment are common, long-term treatment could be rendered ineffective. Therefore, the development of a sustained release method to deliver G-CSF while avoiding immune responses against PEG, and concurrently assess neutrophil function could greatly improve the current standard-of-care. There is a need for novel compositions and methods that are useful for improving the reconstitution of neutrophils post-HSCT. There is also a need for compositions and methods that are able to reduce the risk associated with HSCT and improve patient outcomes. SUMMARY OF THE INVENTION Disclosed herein are novel compositions and methods for delivering an active agent to a subject. The composition and methods disclosed herein provide a means to treat and/or prevent diseases associated with a deficiency in levels of functional innate leukocytes, e.g., neutrophils. Accordingly, in one aspect, the present invention provides a method of delivering an active agent to a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, e.g., neutrophils, the method comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby delivering the active agent to the subject. In another aspect, the present invention provides a method of modulating the activity of an innate leukocyte, e.g., neutrophils, restoring levels of functional innate leukocytes, reconstituting the levels of functional innate leukocytes and/or enhancing the regeneration of functional innate leukocytes in a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, the method comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby modulating the activity of an innate leukocyte, reconstituting the levels of innate leukocyte and/or enhancing the regeneration of an innate leukocyte in the subject. In various embodiments of the above aspects or any other aspect of the invention described herein, the active agent (i) modulates the activity of an innate leukocyte; (ii) restores levels of functional innate leukocytes, e.g., neutrophils; (iii) reconstitutes levels of functional innate leukocytes; (iv) enhances the regeneration of functional innate leukocytes in the subject; (v) enhances immunity of the subject in need thereof; and/or (vi) treats or prevents a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes. In another aspect, the present invention provides a method for detecting immune recovery in a subject having a deficiency in levels of functional innate leukocytes, e.g., neutrophils, comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof, assessing the level of degradation of the scaffold composition, wherein degradation of the scaffold composition is indicative of immune recovery in the subject. In various embodiments of the above aspects or any other aspect of the invention described herein, the scaffold composition further comprises an active agent. In some embodiments, the method provides for controlled, sustained, and/or delayed release of the active agent upon administration to the subject. In some embodiments, the method provides for sustained release of the active agent upon administration to the subject. In some embodiments, the method provides for controlled release of the active agent upon administration to the subject. In some embodiments, the method provides for delayed release of the active agent upon administration to the subject. In some embodiments, the release of the active agent is delayed at least about 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or more days after administration. In various embodiments of the above aspects or any other aspect of the invention described herein, degradation of the scaffold composition is indicative of (i) modulation of the activity of an innate leukocyte; restoration of levels of functional innate leukocytes, e.g., neutrophils; reconstitution of levels of functional innate leukocytes; regeneration of functional innate leukocytes in the subject; enhanced immunity of the subject; and/or treatment or prevention of a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes. In various embodiments of the above aspects or any other aspect of the invention described herein, the scaffold composition degrades upon exposure to functional innate leukocytes, e.g., neutrophils. In some embodiments, the innate leukocyte: (i) is selected from the group consisting of a natural killer cell, a mast cell, an eosinophil, a basophil, a macrophage, a dendritic cell, a gamma-delta (γδ) T cell, and a neutrophil; and/or (ii) is not a dendritic cell. In some embodiments, the innate leukocyte comprises a neutrophil. In some embodiments, the active agent comprises an amino acid, a peptide, a protein, a nucleic acid, an oligonucleotide, a small molecule, or a combination thereof. In some embodiments, the active agent comprises a protein, optionally, wherein the protein is an isolated protein and/or a recombinant protein. In some embodiments, the active agent comprises a cytokine, a chemokine, and/or a growth factor. In some embodiments, the active agent comprises a cytokine, optionally, a pro-inflammatory cytokine and/or an anti- inflammatory cytokine. In some embodiments, the active agent is selected from the group consisting of a granulocyte colony stimulating factor (G-CSF), a granulocyte-macrophage colony-stimulating factor (GM-CSF), a bone morphogenetic protein 2 (BMP2), a stromal cell-derived factor (SDF), a platelet activating factor (PAF), a tumor necrosis factor α (TNFα), an interleukin-1 (IL-1), an interleukin-1α (IL-1α), an interleukin-1β (IL-1β), an interleukin-2 (IL-2), an interleukin-3 (IL-3), an interleukin-4 (IL-4), an interleukin-5 (IL-5), an interleukin- 6 (IL-6), an interleukin-7 (IL-7), an interleukin-8 (IL-8), an interleukin-9 (IL-9), an interleukin-10 (IL-10), an interleukin-11 (IL-11), an interleukin-12 (IL-12), an interleukin-13 (IL-13), an interleukin-14 (IL-14), an interleukin-15 (IL-15), an interleukin-16 (IL-16), an interleukin-17 (IL-17), an interleukin-18 (IL-18), an interleukin-19 (IL-19), an interleukin-20 (IL-20), an interleukin-21 (IL-21), an interleukin-22 (IL-22), an interleukin-23 (IL-23), an interleukin-24 (IL-24), an interleukin-25 (IL-25), an interleukin-26 (IL-26), an interleukin-27 (IL-27), an interleukin-28 (IL-28), an interleukin-29 (IL-29), an interleukin-30 (IL-30), an interleukin-31 (IL-31), an interleukin-32 (IL-32), an interleukin-33 (IL-33), an interleukin-34 (IL-34), an interleukin-35 (IL-35), an interleukin-36 (IL-36), an interleukin-1 receptor antagonist (IL-1Ra), a growth-related gene product-α (GRO-α), a growth-related gene product-β (GRO-β), a macrophage infiltrating protein-1α (MCP-1α), a macrophage infiltrating protein-1β (MCP-1β), a cytokine-induced chemoattractant (CINC), an interferon- α (IFN-α), an interferon-β (IFN-β), an interferon-γ (IFN-γ), a Fas ligand (FasL), a CD30 ligand (CD30L), a vascular endothelial growth factor (VEGF), a hepatocyte frowth factor (HGF), a transforming growth factor alpha (TGF-α), an oncostain (OSM), a neurotrophin, a monocyte chemoattractant protein-1 (MCP-1), a stem cell factor (SCF), a complement 5a (C5a), and an erythropoietin (EPO). In some embodiments, the active agent comprises a G- CSF. In some embodiments, the active agent comprises a polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF). In some embodiments, the active agent active agent is G-CSF. In various embodiments of the above aspects or any other aspect of the invention described herein, the method further comprises administering an additional active agent. In some embodiments, the additional active agent is encapsulated in the scaffold. In some embodiments, the additional active agent is administered systemically. In various embodiments of the above aspects or any other aspect of the invention described herein, the subject is or has undergone therapy that depletes or reduces the innate leukocyte in the subject. In some embodiments, the therapy is a chemotherapy or a radiotherapy for the treatment of a cancer. In various embodiments of the above aspects or any other aspect of the invention described herein, the composition further comprises a detectable agent. In some embodiments, the detectable agent is attached to the active agent. In some embodiments, the detectable agent is for detecting the scaffold and/or active agent in vivo. In some embodiments, the detectable agent is for assessing the level of degradation of the scaffold composition. In some embodiments, the detectable agent is selected from the group consisting of a dye, a fluorophore, a fluorescent compound, a luminescent compound, a chemiluminescent compound, a radioisotope, a paramagnetic metal ion, a nanoparticle, and a quantum dot, or a combination thereof. In some embodiments, the detectable agent comprises a dye. In some embodiments, the detectable agent is detectable by eye, fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), multi-mode imaging, ultrasound imaging (USI), photoacoustic imaging (PAI), and/or optical coherence tomography (OCT). In various embodiments of the above aspects or any other aspect of the invention described herein, the method further comprises assessing the level of degradation of the scaffold. In some embodiments, assessing the level of degradation of the scaffold comprises detecting the level of the detectable agent and comparing to a detectable agent reference level, optionally, wherein the detectable agent reference level is the level of the detectable agent upon administration of the scaffold composition or at an earlier time point after administration of the scaffold composition. In various embodiments of the above aspects or any other aspect of the invention described herein, the method further comprises obtaining a measurement of (i) the level of the detectable agent and/or active agent in the scaffold prior to administration of the scaffold to the subject; (ii) the level of functional innate leukocytes, e.g., neutrophils in the subject prior to administration of the scaffold to the subject; (iii) the level of the innate leukocytes in the subject prior to administration of the scaffold to the subject; (iv) the level of the detectable agent and/or active agent in the scaffold after administration of the scaffold to the subject; (v) the level of functional innate leukocytes after administration of the scaffold to the subject; (vi) the level of the innate leukocytes in the subject prior to administration of the scaffold to the subject; (vii) the level of functional innate leukocytes in the subject before the subject receives a therapy that depletes or reduces the level of the innate leukocyte; and/or (viii) the level of functional innate leukocytes in the subject after the subject receives a therapy that depletes or reduces the level of the innate leukocyte. In some embodiments, the level of functional innate leukocytes, e.g., neutrophils is increased by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99% or more as compared to a reference level. In some embodiments, the level of functional innate leukocytes, e.g., neutrophils is increased by at least about 1-fold, about 2-fold, or about 3-fold or more as compared to a reference level. In some embodiments, the reference level is a standardized level. In some embodiments, the reference level is the level of functional innate leukocytes, e.g., neutrophils prior to administration of the scaffold composition or at an earlier time point after administration of the scaffold composition. In various embodiments of the above aspects or any other aspect of the invention described herein, the scaffold composition does not comprise a differentiation factor that induces the differentiation of a hematopoietic stem cell into a T cell progenitor cell. In various embodiments of the above aspects or any other aspect of the invention described herein, the scaffold composition degrades upon exposure to an enzyme produced by the innate leukocyte. In some embodiments, the scaffold composition degrades by neutrophil-mediated oxidation. In some embodiments, the degradation of the scaffold composition results in and/or enhances the release of the active agent. In some embodiments, the degradation of the scaffold composition results in and/or enhances the release of the detectable agent. In various embodiments of the above aspects or any other aspect of the invention described herein, the scaffold is macroporous or wherein the scaffold comprises pores having a diameter of about 50 microns to about 150 microns, about 80 microns to about 180 microns, or about 40 microns to about 90 microns. In various embodiments of the above aspects or any other aspect of the invention described herein, the subject is a human. In various embodiments of the above aspects or any other aspect of the invention described herein, the composition is administered to the subject via injection, optionally, intravenously, intramuscularly, or subcutaneously. In various embodiments of the above aspects or any other aspect of the invention described herein, the subject has a disorder selected from the group consisting of primary neutropenia, acute neutropenia, severe chronic neutropenia (SCN), severe congenital neutropenia (Kostmann's syndrome), severe infantile genetic agranulocytosis, benign neutropenia, cyclic neutropenia, chronic idiopathic neutropenia, secondary neutropenia, syndrome associated neutropenia, and immune-mediated neutropenia, chronic granulomatous disease, Chediak-Higashi syndrome, Griscelli Syndrome-II, Hermansky-Pudlak Syndrome type 2, leukocyte adhesion deficiency, specific granule deficiency, x-linked neutropenia, myeloperoxidase deficiency, and hyper-IgE syndrome. In some embodiments, the subject has a neutropenia, optionally, wherein the neutropenia is caused by or associated with radiation, alcoholism, drugs, allergic disorders, aplastic anemia, autoimmune disease, T-γ lymphoproliferative disease (T-γ LPD), myelodysplasia, myelofibrosis, dysgammaglobulinemia, paroxysmal nocturnal hemoglobinuria, cancer, vitamin B12 deficiency, folate deficiency, viral infection, bacterial infection, spleen disorder, hemodialysis, or transplantation, toxins, bone marrow failure, Schwachman-Diamond syndrome, cartilage-hair hypoplasia, dyskeratosis congenita, glycogen storage disease type IB, splenomegaly of any cause, and intrinsic defects in myeloid cells or their precursors. In some embodiments, the subject has or is receiving a hematopoietic stem cell transplantation (HSCT). In some embodiments, the administration of the composition is prior to, concurrently with, or subsequent to the HSCT. In various embodiments of the above aspects or any other aspect of the invention described herein, the method reconstitutes the innate leukocyte within 7 days, 14 days, 21 days, or 28 days. In some embodiments, the reconstitution of the innate leukocyte results in the level of innate leukocyte to be at least about 75%, 80%, 85%, 90%, 95% or 99% of a reference level. In some embodiments, the reference level is (i) a standardized level; (ii) the level of the innate leukocyte of the subject before depletion of the level of the innate leukocyte; and/or (iii) the level of the innate leukocyte of the subject before the subject receives a therapy the depletes or reduces the level of the innate leukocyte. In various embodiments of the above aspects or any other aspect of the invention described herein, the method results in (i) an increase in the number of the innate leukocytes in the subject; (ii) an increase in the number of functional innate leukocytes, e.g., neutrophils in the subject; (iii) a reduction in the incidence, severity, and/or duration of an opportunistic infection in the subject; (iv) a reduction in the incidence, severity, and/or duration of a symptom of neutropenia in the subject; (v) a reduction in the incidence, severity, and/or duration of a symptom of an immunodeficiency-associated complication in the subject; (vi) an increase in the level of tissue regeneration in the subject; (vii) an increase in the therapeutic efficacy of a therapy that depletes or reduces the innate leukocyte in the subject; (viii) an increase in the degradation of the scaffold in the subject; and/or (ix) an increase in the release of a detectable agent, an active agent, and/or an additional active agent from the scaffold in the subject. In various embodiments of the above aspects or any other aspect of the invention described herein, the subject has or is receiving systemic G-CSF and/or PEG-G-CSF. In some embodiments, the administration of the composition is prior to, concurrently with, or subsequent to the systemic G-CSF and/or PEG-G-CSF. In some embodiments, the method further comprising administering to the subject systemic G-CSF and/or PEG-G-CSF. In some embodiments, the subject has or is at risk of developing anti-PEG antibody (APA)-mediated rapid clearance. In some embodiments, the subject has pre-existing or induced anti-PEG antibody (APA)-mediated rapid clearance. In some embodiments, the subject has failed or is at risk of failing to respond to systemic G-CSF and/or PEG-G-CSF. In another aspect, the present invention provides a method of treating a subject for cancer in need thereof, wherein the subject is undergoing chemotherapy or radiotherapy, comprising administering to a subject suffering from depleted or reduced innate leukocytes, e.g., functional neutrophils, wherein the composition comprises a biodegradable scaffold and a cytokine that enhances the generation of the innate leukocyte; assessing the levels of the innate leukocyte in the subject; administering chemotherapy or radiotherapy to the subject wherein the levels of innate leukocyte have attained a reference level following administration of the composition. In some embodiments, the innate leukocytes are neutrophils. In some embodiments, the cytokine is G-CSF. In some embodiments, the subject is suffering from depleted or reduced innate leukocytes as a result of previous exposure to chemotherapy or radiotherapy. In some embodiments, the reference level is a standardized level, optionally, (i) wherein the reference level is the level of the innate leukocyte of the subject before depletion of the level of the innate leukocyte; and or (ii) the reference level is the level of the innate leukocyte of the subject before the subject receives a therapy the depletes or reduces the level of the innate leukocyte. In another aspect, the present invention provides an injectable composition, comprising a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof, and at least one of (i) an active agent that increases the number of and/or modulates the activity of an innate leukocyte; and/or (ii) a detectable agent that allows for assessment of degradation of the scaffold composition and/or assessment of the levels of functional innate leukocytes, e.g., neutrophils, in vivo. In some embodiments, the injectable composition comprises both the active agent and the detectable agent. In some embodiments, the innate leukocytes are neutrophils. In some embodiments, the active agent is G-CSF. In another aspect, the present invention provides a method for detecting immune recovery in a subject having a deficiency in levels of functional innate leukocytes, e.g., neutrophils, comprising administering the injectable composition of any one of the above aspects or any other aspect of the invention described herein and assessing the degradation of the scaffold composition and/or levels of functional innate leukocytes, e.g., neutrophils, in vivo. In another aspect, the present invention provides a method of modulating the activity of an innate leukocyte, restoring levels of functional innate leukocytes, e.g., neutrophils, reconstituting the levels of functional innate leukocytes and/or enhancing the regeneration of functional innate leukocytes in a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, the method comprising administering to the subject the composition of any one of the above aspects or any other aspect of the invention described herein. Other features and advantages of the invention will be apparent from the following detailed description and drawings. BRIEF DESCRIPTION OF THE DRAWINGS FIGS.1A-1E depict macroporous HA cryogel synthesis and fabrication. FIG.1A shows tetrazine and norbornene functionalization of HA. FIG.1B shows cross linking of tetrazine functionalized hyaluronic acid (HA) and norborene functionalized HA. FIG.1C depicts sub-zero cross-linking process to create macroporous HA cryogels. FIG.1D shows a representative SEM image depicting HA cryogels made from 0.8% and 7% degree of substitution (DOS) tetrazine (Tz) functionalized HA (Tz-HA). Top row scale bar = 500 μm. Bottom row scale bar = 100 μm. FIG.1E shows average pore diameters of HA cryogels made from 0.8% and 7% DOS Tz-HA measured from SEM images (n=3). FIGS.2A-2B show that pore size distribution is unaffected after lyophilization. FIG. 2A shows representative confocal microscopy images of cy5 functionalized HA cryogels after thawing, after lyophilization, and after lyophilization and rehydration. FIG.2B shows pore area quantification analysis using FIJI software. ns-P>0.05. Data in FIG.2B represents mean ± s.d. of n=3 gels. FIGS.3A-3E shows that cross-linking density influences HA degradation. FIG.3A is a schematic showing cy5-conjugated tetrazine functionalization of norbornene functionalized HA and subsequent cross-linked structure after cross-linking with tetrazine functionalized HA. FIG.3B shows a photograph of cy5-conjugated HA-cryogel. FIG.3C shows degradation scores of HA cryogels synthesized with 0.8% and 7% degree of substitution (DOS) tetrazine functionalized hyaluronic acid. FIG.3D shows representative IVIS fluorescence images of gel degradation in mice. FIG.3E shows tracking of HA cryogel degradation by quantification of total radiant efficiency normalized to initial day 3 timepoint. Data in FIGS.3A and 3C represents mean ± s.d. of n=4 HA cryogels. FIGS.4A-4G depict in vivo deployment and gel degradation in models of immunodeficiency. Representative in vivo imaging system (IVIS) fluorescence images of gel degradation and quantification of gel degradation by tracking total radiant efficiency normalized to initial day 3 timepoint of FIG.4A untreated mice, FIG.4B macrophage deficient mice, FIG.4C T-cell deficient mice, FIG.4D B-cell deficient mice, and FIG.4E severely immunodeficient NOD scid gamma (NSG) mice. FIG.4F shows hematoxylin and eosin (H&E) stain of explanted HA cryogels from immune competent mice, T-cell deficient mice, B-cell deficient mice, and macrophage deficient mice at days 1, 5, and 10. FIG.4G depicts an analysis of H&E stains to quantify cell density on outer 50μm of HA cryogel and interior of HA cryogel. Data represents measurements from 2-4 H&E stains for no treatment (immune competent), B-cell deficient, T-cell deficient, and macrophage deficient mice for HA cryogels excised 1 day, 5 days, and 10 days after implant.5 areas are sampled on outer edge and interior of each H&E sample. Data in FIGS.4A-4E represents mean ± s.d. of n=5. Data in FIG.4G represents mean ± s.d. of n=10-20. FIGS.5A-5D shows innate immune cell infiltration into HA cryogels. FIG.5A depicts representative flow cytometry plots of F4-80 and CD11b expression in HA cryogels 1 day after administration. FIG.5B shows representative flow cytometry plots of F4-80 and CD11b expression in HA cryogels 10 days after administration. FIGS.5C-5D depicts FACs quantification of total number of CD45⁺ CD11b⁺ myeloid cells (FIG.5C) and FIG.5D CD45⁺CD11b⁺ F4-80⁺ macrophages (FIG.5D) infiltrating HA cryogels in immune competent mice, T-cell depleted mice, B-cell depleted mice, and macrophage depleted mice. Data in FIGS.5C-5D represents mean ± s.d. of n=4-7 mice. FIGS.6A-6F show that degradation kinetics of HA cryogels is impaired during transient immunodeficiency following bone marrow transplant (BMT). FIG.6A shows the schedule of administration of lethal total body irradiation followed by BMT and simultaneous injection of Cy5-HA cryogel. B6 mice were irradiated with 10Gy (1 dose) 48 hours before transplant with 2 x 10⁵ lineage-depleted syngeneic bone marrow cells. FIG.6B shows epresentative IVIS fluorescence images of gel degradation in both immune competent mice and mice that received a BMT. FIG.6C depicts tracking gel degradation by quantification of total radiant efficiency normalized to initial day 3 timepoint. FIG.6D depicts peripheral blood CD45⁺CD11b⁺ myeloid cells reconstitution after BMT with respect to time. Radiation administered at day -2 for 10Gy radiation group and HA cryogels injected on day 0. FIGS. 6E-6F show cell infiltration of CD45⁺CD11b⁺ myeloid cells (FIG.6E) and CD45⁺CD11b⁺ F4-80⁺ macrophage cells (FIG.6F) into HA cryogels in immune competent mice 5 days after administration and 5, 16, and 21 days following BMT. Data in FIG.6C represents mean ± s.e.m. of n=7-9 mice. Data in FIG.6D represents mean ± s.d. of n=5 mice. Data in FIGS. 6E-6F represents mean ± s.d. of n=4-5 mice. *P<0.05, **P<0.01, ANOVA with a Tukey post hoc test. FIGS.7A-7B shows data from immune lineage depletion studies. FIG.7A depicts flow cytometry representations of peripheral blood stained before and after immune depletion treatments. FIG.7B shows ratio of CD45⁺CD11b⁺F4-80⁺CD80⁺CD86⁺CD206- pro- inflammatory (M1) and CD45⁺CD11b⁺F4-80⁺CD80-CD86-CD206⁺ anti-inflammatory (M2) macrophages associated with HA cryogels excised 1 day and 10 days after implant. FIG.7C shows a graph comparing the ratio of M1:M2 macrophages associated with HA cryogels excised 1 day and 10 days after implant. FIGS.8A-8B depicts data from bone marrow transplant studies. FIG.8A shows flow cytometry plots representing fraction of cells Lineage- before and after hematopoietic stem cell enrichment. FIG.8B shows fraction of CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil to total CD45⁺CD11b⁺ myeloid cells before and after bone marrow transplant. FIGS.9A-9E depict enhanced reconstitution of peripheral blood CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil cells. FIG.9A shows an experimental overview of G-CSF mediated CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil reconstitution study. FIG.9B shows reconstitution of peripheral blood CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophils compiled from FACS quantification. Peripheral blood CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil concentration 7 days (FIG.9C) and 12 days (FIG.9D) after lethal radiation. FIG.9E depicts tracking HA cryogel degradation by quantification of total radiant efficiency normalized to initial day 6 timepoint. Data represents mean ± s.d. of n=5 mice. *P<0.05, **P<0.01, ANOVA with a Tukey post hoc test. FIGS.10A-10B show data from granulocyte colony stimulating (G-CSF) factor bone marrow transplant studies. FIG.10A shows death resulting from twice daily intraperitoneal 100ng G-CSF. FIG.10B shows reconstitution of peripheral blood CD45⁺CD11b⁺CD115- Ly6-G⁺ neutrophils tracked up to 29 days after bone marrow transplant. FIG.11 shows endotoxin levels of HA-Tz and Cy5-HA-Nb were quantified to be less than 5 endotoxin units/kg, the threshold pyrogenic dose for preclinical species. FIGS.12A-12I depict production and characterization of Cy5-HA cryogel. (FIG. 12A shows a schematic for tetrazine (Tz) and norbornene (Nb) functionalization of HA, Cy5 functionalization of Nb functionalized HA (Cy5-HA-Nb) and crosslinking of Tz functionalized HA with Cy5-HA-Nb. FIG.12B depicts a schematic for producing Cy5-HA cryogels. FIG.12C shows a representative photograph of lyophilized Cy5-HA cryogel. Scale bar = 1mm. FIG.12D shows a representative SEM image depicting Cy5-HA cryogels. Top scale bar = 1mm, middle scale bar = 500μm, bottom scale bar = 100μm. FIG.12E shows a confocal microscopy image, overhead and side views, depicting hydrated Cy5-HA cryogels pre- and post-injection incubated with 10μm FITC-labeled microparticles. Scale bar = 100μm. FIG.12F shows a schematic depicting workflow for in vitro Cy5-HA cryogel degradation study. FIG.12G depicts measuring Cy5-HA cryogel degradation in vitro by quantifying the Cy5-signal in supernatant at pre-determined timepoints normalized to total Cy5-signal in supernatant across all timepoints. FIG.12H shows a schematic depicting workflow for in vivo Cy5-HA cryogel degradation study. FIG.12I shows representative in vivo imaging system (IVIS) fluorescence images of gel degradation in mice and measuring Cy5-HA cryogel degradation in vivo by quantification of total radiant efficiency normalized to initial day 3 timepoint. IVIS Images are on the same scale and analyzed using Living Image Software. Data in FIG.12G represents mean ± s.d. of n=4 HA cryogels. Data in FIG. 12I represents mean ± s.e.m. of n=4 HA cryogels. Part of FIGS.12B, 12F and 12H were created with BioRender.com. FIGS.13A-13H depict HA cryogel materials characterization data. FIG.13A shows volumetric swelling ratios for low- and high-DOS Cy5-HA cryogels. FIG.13B shows aqueous weight percentage of low- and high-DOS Cy5-HA cryogels. FIG.13C shows a representative SEM image depicting low-DOS Cy5-HA cryogels. Top scale bar = 500μm, bottom scale bar = 100μm. FIG.13D depicts average pore diameters of HA cryogels made from low- and high-DOS Cy5-HA cryogels measured from SEM images (20 measurements/cryogel, n = 3 each for low and high-DOS HA cryogels). FIG.13E shows confocal microscopy images, overhead and side views, depicting low-DOS Cy5-HA cryogels both pre-injection and post-injection incubated with 10μm FITC-labeled microparticles. Scale bar = 100μm. FIG.13F depicts the quantification of confocal images showing penetration of 10μm FITC-labeled microparticles into both low- and high-DOS Cy5-HA cryogels pre- and post-injection. FIG.13G shows representative confocal microscopy images of low- and high- DOS Cy5-HA cryogels after thawing, after lyophilization, and after lyophilization and rehydration. FIG.13H depicts average surface pore diameter of Cy5-HA cryogels measured from confocal images. Data in FIG.13A and FIG.13B represents mean ± s.d. of n=10 Cy5- HA cryogels. Data in FIG.13D represents mean ± s.d. of n=3 Cy5-HA cryogels and was compared using student’s t-test. Data in FIG.13F represents mean ± s.d. of n=5 Cy5-HA cryogels. Data in FIG.13H represents mean ± s.d. of n=3 HA cryogels and was compared using student’s t-test. FIGS.14A-14C depict Cy5-HA cryogel degradation characterization data. FIG.14A depicts measuring low-DOS Cy5-HA cryogel degradation in vitro by quantification of Cy5- signal in supernatant at pre-determined timepoints normalized to total Cy5-signal in supernatant across all timepoints. FIG.14B shows representative IVIS fluorescence images of gel degradation in mice and measuring low-DOS Cy5-HA cryogel degradation in vivo by quantification of total radiant efficiency normalized to the initial day 3 timepoint. FIG.14C depicts measuring Cy5-HA cryogel degradation by quantification of total radiant efficiency normalized to initial day 3 timepoint. Data in FIG.14A represents mean ± s.e.m. of n=4 HA cryogels. Data in FIG.14B represents mean ± s.e.m. of n=4 HA cryogels. Data in FIG.14C represents mean ± s.d. of n=4-5 HA cryogels and were compared using two-way ANOVA with Bonferroni’s multiple comparison test. FIGS.15A-15F depict Cy5-HA cryogel degradation in immunodeficient mice. Representative IVIS fluorescence images of Cy5-HA cryogel degradation and quantification by measuring total radiant efficiency normalized to initial day 3 timepoint of untreated B6 mice (FIG.15A), neutrophil depleted B6 mice (FIG.15B), macrophage depleted B6 mice (FIG.15C), and NSG mice (FIG.15D). IVIS Images are on the same scale and analyzed using Living Image Software. FIG.15E shows hematoxylin and eosin (H&E) stained histological sections of explanted Cy5-HA cryogels from the above groups, at days 1, 5, and 10 post-injection. Full view scale bar = 800μm, magnified scale bar = 100μm. FIG.15F shows quantification of cellular density in the sections from FIG.15E. Data in FIGS.15A- 15D represent mean ± s.e.m. of n=4-9 and are representative of at least two separate experiments. Data in FIG.15F represents mean ± s.d. of n=7-12 and were compared using student’s t-test. FIGS.16A-16L show Cy5-HA cryogel degradation in immunodeficient mice characterization data. FIGS.16A-16B show representative IVIS fluorescence images of gel degradation and quantification by measuring total radiant efficiency normalized to initial day 3 timepoint of T cell depleted B6 mice (FIG.16A) and B cell depleted B6 mice (FIG.16B). FIG.16C shows a representative flow cytometry plot of peripheral blood neutrophils pre- and post-administration of neutrophil depleted mice and FIG.16D shows peripheral blood neutrophil concentration. FIG.16E shows a representative flow cytometry plot of peripheral blood monocytes pre- and post- administration clodronate liposomes to mice and FIG.16F peripheral blood monocyte concentration. FIG.16G shows a representative flow cytometry plot of peripheral blood T cells blood pre- and post- administration of anti-CD4 and anti-CD8 antibody treatment to mice and FIG.16H shows peripheral blood T cell concentration. FIG. 16I shows a representative flow cytometry plot of peripheral blood B cells blood pre- and post- administration of anti-B220 antibody treatment to B6 mice and FIG.16J shows peripheral blood B cell concentration. FIG.16K shows an overlay of normalized total radiant efficiency curves and time to 50% fluorescence intensity of untreated B6, neutrophil depleted, macrophage depleted, T cell depleted, and B cell depleted mice. FIG.16L shows a photograph of a Cy5-HA cryogel retrieved from NSG mice 3 months post-injection. Data in FIG.16A-16B represents mean ± s.e.m. of n=5 and are representative of at least two separate experiments. Data in FIG.16D, 16F, 16H, 16J represents mean ± s.d. of n=4-5. Data in FIG. 16K represents mean ± s.d. of n=4-9 and were compared using student’s t-test. FIGS.17A-17B depict a histomorphometric analysis of Cy5-HA cryogels retrieved from T- and B- cell depleted mice. FIG.17A shows a hematoxylin and eosin (H&E) stain of explanted Cy5-HA cryogels from T cell depleted and B cell depleted mice at days 1, 5, and 10. Scale bar left = 800μm, scale bar right = 100μm. FIG.17B shows an analysis of H&E stains to quantify cellular density in Cy5-HA cryogel. Data in FIG.17B represents mean ± s.d. of n = 7-12 histological sections and was compared using student’s t-test. FIGS.18A-18G show an assessment of innate immune cell infiltration into Cy5-HA cryogels. FIG.18A depicts a schematic for the quantification of innate immune cell content in Cy5-HA cryogels. FIG.18B shows representative flow cytometry plots depicting gating strategy to determine cellular identity of CD45⁺ CD11b⁺ F4/80⁺ (macrophage) cells, CD45⁺ CD11b⁺ F4/80- Ly6G⁺ (neutrophil) cells, and CD45⁺ CD11b⁺ F4/80- Ly6G- CD115⁺ (monocyte) cells in untreated B6 mice, anti-Ly6G and anti-rat κ immunoglobulin light chain antibody treated B6 mice, clodronate liposome treated B6 mice, and NSG mice. FIGS.18C- 18E show quantification of total number of CD45⁺ CD11b⁺ (myeloid) cells (FIG.18C), macrophages (FIG.18D), and neutrophils (FIG.18E) infiltrating HA cryogels in untreated B6 mice, anti-Ly6G and anti-rat κ immunoglobulin light chain antibody treated B6 mice, clodronate liposome treated B6 mice, and NSG mice. FIG.18F shows a schematic depicting workflow for in vivo Cy5-HA cryogel degradation study with gp91^phox- mice. FIG.18G shows representative IVIS fluorescence images of gel degradation and quantification by measuring total radiant efficiency normalized to initial day 3 timepoint of gp91^phox- mice and B6 mice. IVIS Images are on the same scale and analyzed using Living Image Software. Data in FIGS.18C-18E represents mean ± s.d. of n=7-10 Cy5-HA cryogels, are representative of at least two separate experiments and compared using student’s t-test. Data in FIG.18G represents mean ± s.e.m. of n=4-5 and were compared using two-way ANOVA with Bonferroni’s multiple comparison test. Parts of FIGS.18A, 18F were created with BioRender.com. FIGS.19A-19H depict a supplementary analysis of myeloid cell infiltration of Cy5- HA cryogels retrieved from immunodeficient mice. FIG.19A shows representative flow cytometry plots gated to determine cellular identity of CD45⁺ CD11b⁺ F4/80⁺ (macrophage) cells, CD45⁺ CD11b⁺ F4/80- Ly6G⁺ (neutrophil) cells, and CD45⁺ CD11b⁺ F4/80- Ly6G- CD115⁺ (monocyte) cells T cell depleted and B cell depleted mice. FIG.19B shows percent of AnnexinV- (live) cells within Cy5-HA cryogels one and ten days after implant from flow cytometry analysis. FIGS.19C-19D depict the quantification of total number of myeloid cells (FIG.19C) and macrophages (FIG.19D) infiltrating Cy5-HA cryogels in untreated B6 mice, T cell depleted mice, and B cell depleted mice. FIG.19E shows representative flow cytometry plots from neutrophil depleted mice with and without intracellular Ly6G staining. Plotted data assessing neutrophils as a percentage of total myeloid cells (CD45⁺CD11b⁺) with and without intracellular Ly6G staining. FIG.19F shows the quantification of total number of neutrophils infiltrating Cy5-HA cryogels in untreated B6 mice, T cell depleted mice, and B cell depleted mice. FIGS.19G-19H depicts the quantification of total number of monocytes (FIG.19G) and infiltrating immune cell lineages (FIG.19H) plotted as a percentage of myeloid cells in untreated, neutrophil depleted, macrophage depleted, T cell depleted, B cell depleted, and NSG mice. Data in FIG.19E represents mean ± s.d. of n = 10. Data in FIGS. 19B-19H represents mean ± s.d. of n = 7-10 and are representative of at least two separate experiments. Data in FIGS.19C-19F were compared using student’s t-test. FIGS.20A-20C depict immunohistochemical staining of Cy5-HA cryogels retrieved from untreated B6 and NSG mice. FIG.20A shows immunohistochemistry (IHC) staining for Ly6G (neutrophils, top, scale bar = 1mm) and F4/80 (macrophages, bottom, scale bar = 60μm) of Cy5-HA cryogels excised from untreated B6 mice 1-, 5-, and 10-days after injection. IHC was conducted on the same Cy5-HA cryogels as in FIG.15E. FIG.20B shows IHC staining for Ly6G (top, scale bar = 1mm) and F4/80 (bottom, scale bar = 60μm) of Cy5-HA cryogels excised from macrophage depleted, neutrophil depleted, T cell depleted, and B cell depleted B6 mice 1-day after injection. IHC was conducted on the same Cy5-HA cryogels as in FIG.15E. FIG.20C shows IHC staining for Ly6G (top, scale bar = 1mm) and F4/80 (bottom, scale bar = 60μm) of Cy5-HA cryogels excised from NSG mice 1-, 5-, and 10-days after injection. IHC was conducted on the same Cy5-HA cryogels as in FIG.15E. FIGS.21A-21G shows supplementary data for degradation kinetics of HA cryogels post-HSCT. FIG.21A shows representative flow cytometry plots of bone marrow before and after lineage depletion. FIG.21B shows time to 50% fluorescence intensity of Cy5-HA cryogels in non-irradiated and post-HSCT mice. FIG.21C shows percent of AnnexinV- (live) cells within Cy5-HA cryogels 5- and 16-days post injection in non-irradiated mice and 5-, 16-, 21-, and 26-days post-injection in post-HSCT mice. FIG.21D depicts infiltrating immune cell lineages plotted as a percentage of myeloid cells in non-irradiated and post- HSCT mice. FIG.21E shows a schematic for tetrazine (Tz) and norbornene (Nb) functionalization of oxidized alginate (OxAlg), Cy5 functionalization of Nb functionalized OxAlg, and crosslinking of Tz functionalized HA with Cy5 functionalized OxAlg. FIG.21F depicts measuring Cy5-OxAlg cryogel degradation in vitro by quantifying the Cy5-signal in supernatant at pre-determined timepoints normalized to total Cy5-signal in supernatant across all timepoints. FIG.21G shows representative in vivo imaging system (IVIS) fluorescence images of gel degradation in mice and measuring Cy5-tagged 40% oxidized alginate cryogel degradation in vivo by quantification of total radiant efficiency normalized to initial 2-hour timepoint. IVIS Images are on the same scale and analyzed using Living Image Software. Data in FIG.21B represents n=7-9 Cy5-HA cryogels, is representative of at least two separate experiments and were compared using student’s t-test. Data in FIG.21C-21D represents mean ± s.d. of n=6-10 Cy5-HA cryogels and is representative of at least two separate experiments. Data in FIG.21G represents mean ± s.e.m. of n=5 Cy5-OxAlg cryogels and were compared using two-way ANOVA with Bonferroni’s multiple comparison test. FIGS.22A-22F shows that degradation kinetics of HA cryogels is impaired during transient immunodeficiency following HSCT. FIG.22A shows a schematic depicting workflow for quantification of Cy5-HA cryogel degradation and innate immune cell infiltration in control (non-irradiated mice that do not receive a transplant) and post-HSCT B6 mice. FIG.22B shows representative IVIS fluorescence images of gel degradation in non-irradiated and post-HSCT mice. Tracking gel degradation by quantification of total radiant efficiency normalized to initial day 3 timepoint. FIG.22C shows a photograph of Cy5-HA cryogels in non-irradiated mice 5- and 16-days post-injection and post-HSCT mice on days 5, 16, 21, and 26. FIGS.22D-22F show cell infiltration of CD45⁺CD11b⁺ (myeloid) cells (FIG.22D), CD45⁺CD11b⁺ F4/80⁺ (macrophage) cells (FIG.22E), and CD45⁺ CD11b⁺ F4/80- Ly6G⁺ (neutrophil) cells (FIG.22F) into HA cryogels in non-irradiated mice 5- and 16-days post-injection and 5-, 16-, 21-, and 26- days post-HSCT. Data in FIG.22B represents mean ± s.e.m. of n = 7-9 mice and is representative of at least two separate experiments. Data in FIGS.22D-22F represents mean ± s.d. of n = 6-10 HA cryogels and are representative of at least two separate experiments. Data in FIG.22B were compared using two-way ANOVA with Bonferroni’s multiple comparison test. Data in FIGS.22D-22F were compared using student’s t-test. Part of FIG.22A was created with BioRender.com. FIGS.23A-23E shows enhanced reconstitution of peripheral blood neutrophil cells. FIG.23A shows a schematic depicting outline of study to quantify Cy5 G-CSF release from HA cryogels in non-irradiated, non-transplanted B6 mice and post-HSCT B6 mice. FIG.23B shows representative IVIS fluorescence images of Cy5 G-CSF release from HA cryogels and quantification by measuring total radiant efficiency normalized to initial 8-hour timepoint. IVIS Images are on the same scale and analyzed using Living Image Software. FIG.23C shows a schematic depicting outline of study to quantify neutrophil reconstitution rate and Cy5-HA cryogel degradation rate in post-HSCT mice using G-CSF encapsulated Cy5-HA cryogels. FIG.23D depicts peripheral blood reconstitution of neutrophils in post-HSCT mice. FIG.23E shows representative in vivo imaging system (IVIS) fluorescence images of gel degradation in mice and measuring Cy5-HA cryogel degradation in vivo by quantification of total radiant efficiency normalized to initial day 3 timepoint. IVIS Images are on the same scale and analyzed using Living Image Software. Data in FIG.23B represents mean ± s.e.m. of n = 6-9 mice. Data in FIG.23D represents mean ± s.d. of n = 11-15 mice and is representative of at least two separate experiments. Data in FIG.23E represents ± s.e.m. of n = 11-14 Cy5-HA cryogels and is representative of at least two separate experiments. Data in FIGS.23B, 23E were compared using two-way ANOVA with Bonferroni’s multiple comparison test. Data in FIG.23D were compared using mixed-effect regression model with random intercepts. Parts of FIG.23A, 23C were created with BioRender.com. FIG.24 shows data for G-CSF release from HA cryogels. Time to 50% fluorescence intensity for Cy5 G-CSF encapsulated within HA cryogels in non-irradiated and post-HSCT mice. Data was compared using students t-test. FIG.25 is a table summarizing various methods and durability of immune cell depletion. DETAILED DESCRIPTION OF THE INVENTION I. DEFINITIONS In order that the present invention may be more readily understood, certain terms are first defined. Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. In addition, it should be noted that whenever a value or range of values of a parameter are recited, it is intended that values and ranges intermediate to the recited values are also intended to be part of this invention. The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural (i.e., one or more), unless otherwise indicated herein or clearly contradicted by context. The terms “comprising, “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value recited or falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited. The term “including” is used herein to mean, and is used interchangeably with, the phrase “including but not limited to”. The term “or” is used herein to mean, and is used interchangeably with, the term “and/or,” unless context clearly indicates otherwise. The term “about” or “approximately” usually means within 5%, or more preferably within 1%, of a given value or range. The term “at least” prior to a number or series of numbers is understood to include the number adjacent to the term “at least”, and all subsequent numbers or integers that could logically be included, as clear from context. When at least is present before a series of numbers or a range, it is understood that “at least” can modify each of the numbers in the series or range. As used herein, “no more than” or “less than” is understood as the value adjacent to the phrase and logical lower values or integers, as logical from context, to zero. When “no more than” is present before a series of numbers or a range, it is understood that “no more than” can modify each of the numbers in the series or range. As used herein, ranges include both the upper and lower limit. As used herein, the various forms of the term "modulate" or “alter” are intended to include stimulation, activation, and/or enhancement (e.g., increasing or upregulating a particular response, level, or activity) and inhibition (e.g., decreasing or downregulating a particular response, level, or activity). “Therapeutically effective amount,” as used herein, is intended to include the amount of an active agent or composition that, when administered to a patient for treating a subject having a subject suffering from or susceptible to a disease, disorder, and/or condition, is sufficient to treat, alleviate, ameliorate, relieve, alleviate symptoms of, prevent, delay onset of, inhibit progression of, reduce severity of, and/or reduce incidence of the disease, disorder, or condition, or one or more symptoms of the disease, disorder, or condition, or its related comorbidities). Determination of an effective amount is well within the capability of those skilled in the art. Generally, the actual effective amount can vary with the specific compound, the use or application technique, the desired effect, the duration of the effect and side effects, the subject’s history, age, condition, sex, as well as the severity and type of the medical condition in the subject, the types of preceding or concomitant treatments, if any, the administration of other pharmaceutically active agents, and other individual characteristics of the subject to be treated. Accordingly, an effective dose of an active agent described herein is an amount sufficient to produce at least some desired therapeutic effect in a subject. In one embodiment, the amount is a therapeutically effective amount. As used herein, the term “agent,” “active agent,” or “therapeutic agent” is defined as any chemical entity that has certain function or activity. An active agent includes, but is not limited to an atom, a chemical group, a small molecule organic compound, an inorganic compound, a nucleoside, a nucleotide, a nucleobase, a sugar, a nucleic acid, an amino acid, a peptide, a polypeptide, a protein, a fusion protein, or a protein complex. The agent may be detected by methods known in the art. For example, an agent or moiety may be chemiluminescent or fluorescent and can be detected by any suitable detection assays known in the art. The function or activity of an agent may include any physical, chemical, biological, or physiological function or activity. In certain embodiments, the term “active agent” or “therapeutic agent” refers to any agent that, when administered to a subject, has a therapeutic, prophylactic, and/or diagnostic effect and elicits a desired biological and/or pharmacological effect. Generally, the term “treatment” or “treating” is defined as the application or administration of an active agent to a subject, or application or administration of an active agent to an isolated tissue or cell line from a subject, said subject having a disease, a symptom of disease or a predisposition toward a disease, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect the disease, the symptoms of disease or the predisposition toward disease. Thus, treating can include suppressing, inhibiting, preventing, treating, or a combination thereof. Treating refers, inter alia, to increasing time to sustained progression, expediting remission, inducing remission, augmenting remission, speeding recovery, increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof. “Suppressing” or “inhibiting”, refers, inter alia, to delaying the onset of symptoms, preventing relapse to a disease, decreasing the number or frequency of relapse episodes, increasing latency between symptomatic episodes, reducing the severity of symptoms, reducing the severity of an acute episode, reducing the number of symptoms, reducing the incidence of disease-related symptoms, reducing the latency of symptoms, ameliorating symptoms, reducing secondary symptoms, reducing secondary infections, prolonging patient survival, or a combination thereof. In one embodiment the symptoms are primary, while in another embodiment, symptoms are secondary. “Primary” refers to a symptom that is a direct result of a disorder, e.g., diabetes, while, secondary refers to a symptom that is derived from or consequent to a primary cause. Symptoms may be any manifestation of a disease or pathological condition. Accordingly, as used herein, the term “treatment” or “treating” includes any administration of a composition described herein and includes: (i) preventing the disease from occurring in a subject which may be predisposed to the disease but does not yet experience or display the pathology or symptomatology of the disease; (ii) inhibiting the disease in an subject that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., arresting further development of the pathology and/or symptomatology); or (iii) ameliorating the disease in a subject that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., reversing the pathology and/or symptomatology). In some embodiments, the efficacy of compositions as described herein in, e.g., the treatment of a condition described herein can be determined by the skilled clinician. However, a treatment is considered "effective treatment," as the term is used herein, if one or more of the signs or symptoms of a condition described herein are altered in a beneficial manner, other clinically accepted symptoms are improved, or even ameliorated, or a desired response is induced e.g., by at least 10% following treatment according to the methods described herein. Efficacy can be assessed, for example, by measuring a marker, indicator, symptom, and/or the incidence of a condition treated according to the methods described herein or any other measurable parameter appropriate, e.g., absolute neutrophil count. Efficacy can also be measured by a failure of an individual to worsen as assessed by hospitalization, or need for medical interventions (i.e., progression of the disease is halted). Methods of measuring these indicators are known to those of skill in the art and/or are described herein. In some embodiments, successful treatment can be determined, for example, by measurement of absolute counts for individual blood cell types (e.g., white blood cells, red blood cells, and/or platelets) in the peripheral blood, reaching a number of cells accepted by those of skill in the art as within the normal range for the subject. Methods of conducting a complete blood count, a differential leukocyte count (e.g., including counts of each type of white blood cell, e.g., neutrophils, eosinophils, basophils, monocytes, and lymphocytes), and platelet counts are known to those skilled in the art. Briefly, post-administration of an effective dosage of the compositions described herein, the blood can be collected at regular intervals in a tube containing an anti-coagulant like the EDTA, the cells can be counted using an automated blood count analyzer or manually using a hemocytometer. Neutrophils are a type of white blood cell that are a marker of engraftment; the absolute neutrophil count (ANC) must be at least within the typical normal range for the treatment to be effective. The efficacy of a given therapeutic regimen involving methods and compositions described herein, may be monitored, for example by convention FACS assays for phenotypes of cells in the blood circulation of the subject under treatment. Such analysis is useful to monitor changes in the numbers and/or function of cells of various lineages, e.g., cells of the myeloid lineage. By “treatment”, “prevention” or “amelioration” of a disease or disorder is meant delaying or preventing the onset of such a disease or disorder, reversing, alleviating, ameliorating, inhibiting, slowing down or stopping the progression, aggravation or deterioration the progression or severity of a condition associated with such a disease or disorder. In one embodiment, the symptoms of a disease or disorder are alleviated by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% or more.. In some embodiments, “preventing” or “prevention” refers to a reduction in risk of acquiring a disease or disorder (i.e., causing at least one of the clinical symptoms of the disease not to develop in a subject that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease). Efficacy of treatment is determined in association with any known method for diagnosing the disorder. Alleviation of one or more symptoms of the disorder indicates that the composition confers a clinical benefit. Any of the therapeutic methods described to above can be applied to any suitable subject including, for example, mammals such as dogs, cats, cows, horses, rabbits, monkeys, and most preferably, humans. “Suppressing,” “reducing,” or “inhibiting,” refers, inter alia, to delaying the onset of symptoms, preventing relapse to a disease, decreasing the number or frequency of relapse episodes, increasing latency between symptomatic episodes, reducing the severity of symptoms, reducing the severity of an acute episode, reducing the number of symptoms, reducing the incidence of disease-related symptoms, reducing the latency of symptoms, ameliorating symptoms, reducing secondary symptoms, reducing secondary infections, prolonging patient survival, or a combination thereof. In one embodiment the symptoms are primary, while in another embodiment, symptoms are secondary. “Primary” refers to a symptom that is a direct result of a disorder, e.g., diabetes, while, secondary refers to a symptom that is derived from or consequent to a primary cause. Symptoms may be any manifestation of a disease or pathological condition. The terms "decrease", "reduced", "reduction", or "inhibit" are all used herein to mean a decrease by a statistically significant amount. In some embodiments, the terms "reduced", "reduction", "decrease", or "inhibit" can mean a decrease by at least 5% as compared to a reference level, for example a decrease by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% or more as compared to a reference level. In some embodiments, the terms can represent a 100% decrease, i.e. a non-detectable level as compared to a reference level. The terms "increased", "increase", "enhance", or "activate" are all used herein to mean an increase by a statically significant amount. In some embodiments, the terms "increased", "increase", "enhance", or "activate" can mean an increase of at least 5% as compared to a reference level, for example an increase of at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% or more. In some embodiments, the terms can represent an increase up to and including a 100% increase as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10-fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level. In the context of a marker or symptom, an "increase" is a statistically significant increase in such level. As used herein, the term “immune responsive degradation” generally refers to a material that degrades or dissolves in response to changes in the immune system of a subject. In some embodiments, changes in the immune system of a subject include, but are not limited to, changes in the number and/or function of an immune cell. In some embodiments, changes in the immune system of a subject effect degradation of hylaronic acid (HA), for example, by myeloid cells through enzymatic action and by neutrophil-mediated oxidation. Accordingly, immune responsive degradation of the material can include myeloid responsive degradation and/or neutrophil-responsive degradation to sustain or control the release of an agent from the material. As used herein, the term “controlled release” refers to an agent-containing formulation, such as a composition or scaffold as described herein, in which release of the agent is not immediate, i.e., with a “controlled release” formulation, administration does not result in immediate release of the agent. The term is used interchangeably with “nonimmediate release” as defined in Remington: The Science and Practice of Pharmacy, Nineteenth Ed. (Easton, PA: Mack Publishing Company, 1995). In some embodiments, the term “controlled release” as used herein refers to “sustained release” rather than to “delayed release” formulations. In some instances, the controlled release of the agent from a material is based, at least in part, on the immune responsive degradation of the material. In some instances, the immune responsive degradation of the material includes myeloid responsive degradation and/or neutrophil-responsive degradation to control the release of an agent from the material. The term “sustained release” (synonymous with “extended release”) is used in its conventional sense to refer to a formulation, such as a composition or scaffold as described herein, that provides for gradual release of an agent over an extended period of time. In some instances, the sustained release of the agent from a material is based, at least in part, on the immune responsive degradation of the material. In some instances, the immune responsive degradation of the material includes myeloid responsive degradation and/or neutrophil- responsive degradation to sustain the release of an agent from the material. The term “delayed release” is used in its conventional sense to refer to a formulation, such as a composition or scaffold as described herein, in which there is a time delay between administration of the formulation and the release of the agent therefrom. “Delayed release” may or may not involve gradual release of agent over an extended period of time, and thus may or may not be “sustained release.” In some instances, the delayed release of the agent from a material is based, at least in part, on the immune responsive degradation of the material. In some instances, the immune responsive degradation of the material includes myeloid responsive degradation and/or neutrophil-responsive degradation to sustain or control the release of an agent from the material. In some embodiments, the active agents are delivered in a formulation to provide delayed release at a pre-determined time following administration. In some embodiments, the active agents are delivered in a formulation to provide delayed release based, at least in part, on the immune responsive degradation of the material following administration. In some embodiments, the active agents are delivered in a formulation to provide delayed release based, at least in part, on the number and/or function of neutrophils of and the material following administration. The delay may be up to about 6 hours, about 12 hours, about 1 days, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks, about 11 weeks, about 12 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, or about 12 months or more. Preferably, the delay is about 1 days, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 1 week, or about 2 weeks. Without wishing to be bound by theory, after autologous hematopoietic stem cell transplantation (HSCT) a subject may benefit from a delay in the release of an agent, such as a granulocyte colony stimulating factor (G-CSF), from a composition or scaffold herein to enhanced post- HSCT neutrophil recovery. In one aspect, the present invention advantageously utilizes neutrophil-responsive degradation to sustain the release of a G-CSF from hylaronic acid (HA) hydrogels or HA cryogels. In such a manner, the delayed release period provides sufficient time for immune recovery in a subject, during which hematopoietic stem cells can reestablish blood cell production in the subject whose bone marrow or immune system is damaged or defective. The "percent release" of an agent is generally described as a percentage of the agent released for a material, such as a composition or scaffold as described herein, versus the total amount of agent encapsulated in the material. In some instances, the percent release of the agent from a material may increase with an increase in the immune responsive degradation of the material. In some instances, the immune responsive degradation of the material includes myeloid responsive degradation and/or neutrophil-responsive degradation to sustain or control the release of an agent from the material. As used herein, the term "immune system" refers to the ensemble, or to any one or more of the components, molecules, substances, structures (e.g. cells, tissue, and organs) and physiologic processes involved in the immune response. As used herein, the term "hematopoietic stem cells" or "HSC" refers to stem cells that can differentiate into the hematopoietic lineage and give rise to all blood cell types such as white blood cells and red blood cells, including myeloid (e.g., monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (e.g., T-cells, B- cells, K-cells). Stem cells are defined by their ability to form multiple cell types (multipotency) and their ability to self-renew. Hematopoietic stem cells can be identified, for example, by cell surface markers such as CD34-, CD133+, CD48-, CD150+, CD244-, cKit+, Scal+, and lack of lineage markers (negative for B220, CD3, CD4, CD8, Macl, Grl, and Terl l9, among others). Stem cell transplants are used to restore the stem cell reservoir when the bone marrow has been destroyed by disease, chemotherapy (chemo), or radiation. Depending on the source of the stem cells, this procedure may be called a bone marrow transplant, a peripheral blood stem cell transplant, or a cord blood transplant. They can all be called hematopoietic stem cell transplants (HSCT). Hematopoietic stem cells (HSC) and progenitors are commonly used to replace the hematopoietic system in patients with hematopoietic malignancies, or patients undergoing high dose chemotherapy. Hematopoietic reconstitution after transplantation encompasses the recovery of optimal numbers of hematopoietic stem cells and hematopoietic cells of both the myeloid and lymphoid lineages and their functions, thereby restoring a functional bone marrow. Methods to determine successful transplant and/or hematopoietic reconstitution are known in the art. The long term repopulating ability of candidate hematopoietic stem cells can be evaluated, e.g., in an in vivo sheep model or an in vivo NOD-SCID mouse model for human HSC. The NOD/SCID mouse is an immunodeficient recipient, which allows the introduction of human, NHP or mouse cells and the determination of stem cell functionality through engraftment, proliferation and differentiation into at least two distinct lineages (typically myeloid and lymphoid). This in vivo reconstitution assay is typically known as the Competitive Repopulating Unit (CRU) or SCID Repopulating Cell (SRC) assay. In humans, for example, successful hematopoietic reconstitution can be determined, by measurement of absolute counts for individual blood cell types (white blood cells, red blood cells and platelets) in the peripheral blood, reaching a number of cells accepted by those of skill in the art as within the normal range for the subject. Methods of conducting a complete blood count, differential leukocyte count, i.e., including counts of each type of white blood cell, for e.g., neutrophils, eosinophils, basophils, monocytes, and lymphocytes, and platelet counts are known to those skilled in the art. Briefly, post- transplantation, the blood can be collected at regular intervals in a tube containing an anti- coagulant like the EDTA, the cells can be counted using an automated blood count analyzer or manually using a hemocytometer. Neutrophils, as defined below, are a type of white blood cell that are a marker of engraftment; the absolute neutrophil count (ANC) must be at least 500 for three days in a row to say that engraftment has occurred. This can occur as soon as 10 days after transplant, although 15 to 20 days is common for patients who are given bone marrow or peripheral blood cells. Umbilical cord blood recipients usually require between 21 and 35 days for neutrophil engraftment. Platelet counts are also used to determine when engraftment has occurred. The platelet count must be between 20,000 and 50,000 (without a recent platelet transfusion). This usually occurs at the same time or soon after neutrophil engraftment, but can take as long as eight weeks and even longer in some instances for people who are given umbilical cord blood. As used herein, the term "hematopoietic progenitor cells" encompasses pluripotent cells which are committed to the hematopoietic cell lineage, generally do not self-renew, and are capable of differentiating into several cell types of the hematopoietic system, such as granulocytes, monocytes, erythrocytes, megakaryocytes, B-cells and T-cells, including, but not limited to, short term hematopoietic stem cells (ST-HSCs), multi-potent progenitor cells (MPPs), common myeloid progenitor cells (CMPs), granulocyte-monocyte progenitor cells (GMPs), megakaryocyte-erythrocyte progenitor cells (MEPs), and committed lymphoid progenitor cells (CLPs). The presence of hematopoietic progenitor cells can be determined functionally as colony forming unit cells (CFU-Cs) in complete methylcellulose assays, or phenotypically through the detection of cell surface markers (e.g., CD45-, CD34+, Terl l9-, CD16/32, CD127, cKit, Seal) using assays known to those of skill in the art. As used herein, the term "functional" as in functional innate leukocytes, such as neutrophils, is meant to describe a viable cell that does not contribute to a disease or disorder in the subject. For example, a functional innate leukocyte or a functional neutrophil can have the normal functions of the cell in vivo. Cell function is generally determined by the combination of the lineage of the cell, the proliferation status of the cell, and the activation status of the cell. The lineage status, proliferation status, and activation status can all be detected, for example, by detecting gene expression, protein expression, or a combination of gene and protein expression. For example,the lineage status of a cell can often be determined by the surface receptors on a cell, which allows for affinity based cell sorting. In one embodiment, functional neutrophils refers to neutrophils characterized by the ability to produce superoxide to perform oxidative burst. Exemplary mouse models that may be useful for assessing neutrophil function associated with oxidative burst are known in the art and include, without limitation, the gp91-phox knockout mice that have neutrophils which lack this ability to produce superoxide to perform oxidative burst. See, e.g., https://www.jax.org/strain/002365; Pollock, J.D. et al. Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat Genet 9, 202-209 (1995); and Banerjee, E.R. & Henderson, W.R., Jr. Role of T cells in a gp91phox knockout murine model of acute allergic asthma. Allergy Asthma Clin Immunol 9, 6 (2013). As used herein, the term “subject” includes any subject who may benefit from being administered a hydrogel, cryogel, or an implantable drug delivery device of the invention comprising, for example, a hyaluronic acid (HA). In some embodiments, the subject may benefit from being administered an HA hydrogel or an HA cryogel. The term “subject” includes animals, e.g., vertebrates, amphibians, fish, mammals, non-human animals, including humans and primates, such as chimpanzees, monkeys and the like. In one embodiment of the invention, the subject is a human. The term “subject” also includes agriculturally productive livestock, for example, cattle, sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, chickens, turkeys, ducks, geese and bees; and domestic pets, for example, dogs, cats, caged birds and aquarium fish, and also so-called test animals, for example, hamsters, guinea pigs, rats and mice. The term "neutrophils" or "polymorphonuclear neutrophils (PMNs)" as used herein, refers to the most abundant type of white blood cells in mammals, which form an essential part of the innate immune system. They form part of the polymorphonuclear cell family (PMNs) together with basophils and eosinophils. Neutrophils are normally found in the blood stream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate toward the site of inflammation. They migrate through the blood vessels, then through interstitial tissue, following chemical signals such as interleukin- 8 (1L-8) and CSa in a process called chemotaxis, the directed motion of a motile cell or part along a chemical concentration gradient toward environmental conditions it deems attractive and/or away from surroundings it finds repellent. A variety of methods can be used to assess neutrophil function. For example, neutrophil function can be determined by assessing the phagocytic ability of neutrophils or assessing their ability to perform other important neutrophil functions such as oxidative burst and degranulation. Additionally, specific biochemical effects of neutrophil activation, such as reactive oxidant release, or hypochlorous acid production following myeloperoxidase (MPO) activation by a population of neutrophils may be evaluated. "Neutropenia" is a condition characterized by an abnormally low number of circulating neutrophils. A patient suffering from neutropenia is at substantial risk for infection and disease, as the diminished number of neutrophils circulating in the blood substantially impairs the ability of the patient to fight any invading microorganisms. Neutropenia itself may be the result of disease, genetic disorders, drugs, toxins, and radiation as well as many therapeutic treatments, such as high dose chemotherapy (HDC) and conventional oncology therapy. For example, although many cancers have been found to be sensitive to extremely high doses of radiation or anti-neoplastic (anti-cancer) drugs, such intensive HDC is not widely used because it not only kills cancerous cells, but also frequently destroys the cells of the hematopoietic system that are responsible for generating the army of neutrophils that are necessary to maintain a functioning immune system. Complete destruction of neutrophil progenitor and precursor cells eliminates the patient's short-term capacity to generate mature neutrophils, thereby severely compromising the patient's ability to combat infection. The patient then becomes "immunocompromised" and subject to opportunistic infection. Such a condition may ultimately result in morbidity and death. Other situations also may be encountered where there has been a severe insult to the hematopoietic system, resulting in a substantial reduction in neutrophils and precursors thereto. Typically, a neutropenic condition is diagnosed based on the absolute neutrophil count (ANC), which is determined by multiplying the percentage of bands and neutrophils on a differential by the total white blood cell count. Typical accepted reference range for absolute neutrophil count (ANC) in adults is about 1500 to about 8000 cells per microliter (μl) of blood. Clinically, an abnormal ANC is fewer than about 1500 cells per ml of peripheral blood. The severity of neutropenia is categorized as mild for an ANC of about 1000 to about 1500 cells per ml, moderate for an ANC of about 500 to about 1000 cells per ml, and severe for an ANC of fewer than about 500 cells per ml. As used herein, the term “administering” to a subject includes dispensing, delivering or applying a composition as described herein to a subject by any suitable route for delivery of the composition to the subject, including delivery by injection. Exemplary modes of administration include, but are not limited to, injection, infusion, instillation, inhalation, or ingestion. “Injection” includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intraventricular, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, sub capsular, subarachnoid, intraspinal, intracerebro spinal, and intrasternal injection and infusion. In preferred embodiments, the compositions are administered by injection, e.g., subcutaneous injection. II. COMPOSITIONS FOR MODULATING INNATE LEUKOCYTES The present invention features compositions and methods for delivering an active agent to a subject. The compositions and methods disclosed herein provide a means to treat and/or prevent diseases associated with a deficiency in levels of functional innate leukocytes, such as neutrophils. The compositions of the present invention include a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent. Without wishing to be bound by theory, functional innate leukocytes, such as neutrophils, can mediate essential host defense against pathogens and are among the earliest responders in tissue injury^1-3. Neutrophil deficiency, termed neutropenia, contributes to opportunistic infections and can impair tissue regeneration in affected individuals ^4-7. In autologous hematopoietic stem cell transplantation (HSCT) pre-conditioning myelosuppressive regimens can contribute to a marked transient post-therapy impairment of neutrophils and render recipients susceptible to immune deficiency-associated complications for up to several weeks ^{6, 8-11}. Post-HSCT neutrophil regeneration follows successful bone marrow engraftment of transplanted hematopoietic cells ^{12, 13}, facilitated by granulocyte colony stimulating factor (G- CSF)-mediated granulopoiesis of hematopoietic cells ^14-16. Neutropenia is typically treated as an emergency and, in a subset of patients, the risk of neutropenia may be prophylactically addressed with post-HSCT subcutaneous injection of recombinant human G-CSF (filgrastim) to facilitate recovery ^{6, 14, 17, 18}. Daily injections are often used as G-CSF has a half-life of only about 3 to about 4 hours, which can be extended, for example, by conjugating G-CSF with polyethylene glycol (PEGylation) ^{19, 20}. However, immune responses against PEG have been demonstrated to enhance clearance of PEG-G-CSF in an antibody-dependent manner²¹. As multiple cycles of PEG-G-CSF treatment are common, long-term treatment can be rendered ineffective. Therefore the present invention provides compositions and sustained release methods for delivering active agents, including G-CSF, while avoiding immune responses against PEG, and for concurrently assessing innate leukocyte, including neutrophil, function to improve the current standard-of-care. In certain aspects, the present invention provides compositions and methods which can improve post-HSCT recovery of functional innate leukocytes, including functional neutrophils, and for concurrently assessing innate leukocyte, including neutrophil, function and recovery. In particular embodiments, the scaffold composition can comprise a biodegradable depot which can be used to prophylactically deliver an active agent, such as G-CSF, to post- HSCT recipients. The depot can comprise a porous injectable scaffold made by low- temperature crosslinking, termed cryogelation, of hyaluronic acid (HA), an easily sourced and readily derivatized anionic glycosaminoglycan, also referred to herein as “HA cryogel.” As a component of the extracellular matrix, endogenous HA is a substrate for degradation by myeloid cells through enzymatic action and by neutrophil-mediated oxidation^22-24. The invention is based, at least in part, on the discovery that the degradation profile of the scaffold compositions, described herein, comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, is responsive to functional innate leukocyte recovery. Without wishing to be bound by theory, immune deficiency and/or the level of functional innate leukocytes, including the level of activated neutrophils, in a subject can impact the rate of degradation of the scaffold compositions described herein and the release of encapsulated active agent. In particular, the immune-responsiveness of the scaffold compositions, described herein, can facilitate the controlled, sustained, and/or delayed release of an encapsulated active agent, such as G-CSF. SCAFFOLDS The composition of the present invention comprise a scaffold, e.g., a polymer scaffold, comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and, optionally, an active agent. The scaffold, e.g., a polymer scaffold, comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof, can have immune responsive degradation behavior. For example, the scaffold can have myeloid responsive, e.g., neutrophil responsive, degradation behavior that can be configured to achieve controlled, sustained, and/or delayed release of the active agent upon administration to the subject. In certain embodiments, the immune responsive degradation of the scaffold and the release of the active agent (i) modulates the activity of an innate leukocyte; (ii) restores levels of functional innate leukocytes, e.g., neutrophils; (iii) reconstitutes levels of functional innate leukocytes; (iv) enhances the regeneration of functional innate leukocytes in the subject; (v) enhances immunity of the subject in need thereof; and/or (vi) treats or prevents a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes. The scaffold can comprise one or more biomaterials. Preferably, the biomaterial is a biocompatible material that is non-toxic and/or non-immunogenic. As used herein, the term "biocompatible material" refers to any material that does not induce a significant immune response or deleterious tissue reaction, e.g., toxic reaction or significant irritation, over time when implanted into or placed adjacent to the biological tissue of a subject. The scaffold can comprise biomaterials that are non-biodegradable or biodegradable. In certain embodiments, the biomaterial can be a non-biodegradable material. Exemplary non-biodegradable materials include, but are not limited to, metal, plastic polymer, or silk polymer. In certain embodiments, the polymer scaffold comprises a biodegradable material. The biodegradable material may be degraded by physical or chemical action, e.g., level of hydration, heat, oxidation, or ion exchange or by cellular action, e.g., elaboration of enzyme, peptides, or other compounds by nearby or resident cells. In certain embodiments, the polymer scaffold comprises a biodegradable material that is a substrate for an endogenous enzyme. In certain embodiments, the polymer scaffold comprises a biodegradable material that is a substrate for an endogenous enzyme that catalyzes the degradation of a hyaluronic acid (HA). In certain embodiments, the polymer scaffold comprises a biodegradable material that is a substrate for a hyaluronoglucosidase, such as a hyaluronidase. In certain embodiments, the polymer scaffold comprises a biodegradable material that is a substrate for a hyaluronidase. In certain embodiments, the polymer scaffold comprises both non- degradable and degradable materials. In some ebodiments, the scaffold composition degrades upon exposure to functional innate leukocytes, e.g., neutrophils. In some embodiments, the innate leukocyte: (i) is selected from the group consisting of a natural killer cell, a mast cell, an eosinophil, a basophil, a macrophage, a dendritic cell, a gamma-delta (γδ) T cell, and a neutrophil; and/or (ii) is not a dendritic cell. In some embodiments, the innate leukocyte comprises a neutrophil. In some embodiments, the scaffold composition can degrade at a predetermined rate based on a physical parameter selected from the group consisting of temperature, pH, hydration status, porosity, the cross-link density, type, and chemistry or the susceptibility of main chain linkages to degradation. In particular embodiments, the scaffold composition can degrade at a rate based on a level of immune deficiency and/or a level of functional innate leukocytes, including a level of activated neutrophils, in a subject. For example, a scaffold composition comprising hyaluronic acid (HA), as described herein, can degrade in a matter of days, e.g., 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or more days, or can degrade in a matter of weeks, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more weeks. Alternatively, the scaffold composition degrades at a predetermined rate based on a ratio of chemical polymers. For example, a high molecular weight polymer comprised of solely lactide degrades over a period of years, e.g., 1-2 years, while a low molecular weight polymer comprised of a 50:50 mixture of lactide and glycolide degrades in a matter of weeks, e.g., 1, 2, 3, 4, 6, or 10 weeks. A calcium cross-linked gels composed of high molecular weight, high guluronic acid alginate degrade over several months (1, 2, 4, 6, 8, 10, or 12 months) to years (1, 2, or 5 years) in vivo, while a gel comprised of low molecular weight alginate, and/or alginate that has been partially oxidized, will degrade in a matter of weeks. In certain embodiments, one or more active agents, disclosed herein, are covalently or non-covalently linked or attached to the scaffold composition. In various embodiments, one or more active agents disclosed herein is incorporated on, into, or present within the structure or pores of, the scaffold composition. In certain embodiments, one or more compounds or proteins (e.g., the growth factors, the differentiation factors, and the homing factors), disclosed herein, are covalently or non- covalently linked or attached to the scaffold composition. In various embodiments, one or more compounds or proteins disclosed herein is incorporated on, into, or present within the structure or pores of, the scaffold composition. In some embodiments, the scaffold comprises biomaterials that are modified, e.g., oxidized or reduced. The degree of modification, such as oxidation, can be varied from about 1% to about 100%. As used herein, the degree of modification means the molar percentage of the sites on the biomaterial that are modified with a functional group. For example, the degree of modification can be about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. It is intended that values and ranges intermediate to the recited values are part of this invention. Exemplary modified biomaterials, e.g., hydrogels or cryogels, include, but are not limited to, oxidized hyaluronic acid, reduced- alginate, oxidized alginate, MA-alginate (methacrylated alginate) or MA-gelatin. In some embodiments, a modified biomaterial, e.g., hydrogels or cryogels, may undergo hydrolytic degradation of the polymer. In certain embodiments, the use of a modified biomaterials, e.g., hydrogels or cryogels, may accelerate degradation of the polymer. Exemplary biomaterials suitable for use as scaffolds in the present invention include glycosaminoglycan, silk, fibrin, MATRIGEL®, poly-ethyleneglycol (PEG), polyhydroxy ethyl methacrylate, polyacrylamide, poly (N-vinyl pyrolidone), (PGA), poly lactic-co- glycolic acid (PLGA), poly e-carpolactone (PCL), polyethylene oxide, poly propylene fumarate (PPF), poly acrylic acid (PAA), polyhydroxybutyric acid, hydrolysed polyacrylonitrile, polymethacrylic acid, polyethylene amine, esters of alginic acid; pectinic acid; and alginate, fully or partially oxidized alginate, hyaluronic acid, carboxy methyl cellulose, heparin, heparin sulfate, chitosan, carboxymethyl chitosan, chitin, pullulan, gellan, xanthan, collagen, gelatin, carboxymethyl starch, carboxymethyl dextran, chondroitin sulfate, cationic guar, cationic starch, and combinations thereof. In certain embodiments, the biomaterial is selected from the group consisting of alginate, fully or partially oxidized alginate, and combinations thereof. The scaffolds of the present invention may comprise an external surface. Alternatively, or in addition, the scaffolds may comprise an internal surface. External or internal surfaces of the scaffolds of the present invention may be solid or porous. Pore size of the scaffolds can be less than about 10 nm, between about 100 nm-20 μm, or greater than about 20 μm, e.g., up to and including 1000 μm in diameter. For example, the pores may be nanoporous, microporous, or macroporous. For example, the diameter of nanopores is less than about 10 nm; the diameter of micropores is in the range of about 100 nm-20 μm; and, the diameter of macropores is greater than about 20 μm, e.g., greater than about 50 µm, e.g., greater than about 100 μm, e.g., greater than about 400 μm, e.g., greater than 600 μm or greater than 800 μm. In some embodiment the diameter of the pore is between about 50 µm and about 80 µm. In some embodiments, the scaffolds of the present invention are organized in a variety of geometric shapes (e.g., discs, beads, pellets), niches, planar layers (e.g., thin sheets). For example, discs of about 0.1-200 millimeters in diameter, e.g., 5, 10, 20, 40, or 50 millimeters may be implanted subcutaneously. The disc may have a thickness of 0.1 to 10 millimeters, e.g., 1, 2, or 5 millimeters. The discs are readily compressed or lyophilized for administration to a patient. An exemplary disc for subcutaneous administration has the following dimensions: 8 millimeters in diameter and 1 millimeter in thickness. In some embodiments, the scaffolds may comprise multiple components and/or compartments. In certain embodiments, a multiple compartment device is assembled in vivo by applying sequential layers of similarly or differentially doped gel or other scaffold material to the target site. For example, the device is formed by sequentially injecting the next, inner layer into the center of the previously injected material using a needle, thereby forming concentric spheroids. In certain embodiments, non-concentric compartments are formed by injecting material into different locations in a previously injected layer. A multi- headed injection device extrudes compartments in parallel and simultaneously. The layers are made of similar or different biomaterials differentially doped with pharmaceutical compositions. Alternatively, compartments self-organize based on their hydro-philic/phobic characteristics or on secondary interactions within each compartment. In certain embodiments, multicomponent scaffolds are optionally constructed in concentric layers each of which is characterized by different physical qualities such as the percentage of polymer, the percentage of crosslinking of polymer, chemical composition of the hydrogel, pore size, porosity, and pore architecture, stiffness, toughness, ductility, viscoelasticity, the growth factors, the differentiation factors, and/or homing factors incorporated therein and/or any other compositions incorporated therein. Hydrogel and Cryogel Scaffolds In certain embodiments, the scaffolds of present invention comprise one or more hydrogels. A hydrogel is a polymer gel comprising a network of crosslinked polymer chains. A hydrogel is usually a composition comprising polymer chains that are hydrophilic. The network structure of hydrogels allows them to absorb significant amounts of water. Some hydrogels are highly stretchable and elastic; others are viscoelastic. Hydrogel are sometimes found as a colloidal gel in which water is the dispersion medium. In certain embodiments, hydrogels are highly absorbent (they can contain over 99% water (v/v)) natural or synthetic polymers that possess a degree of flexibility very similar to natural tissue, due to their significant water content. In certain embodiments, a hydrogel may have a property that, when an appropriate shear stress is applied, the deformable hydrogel is dramatically and reversibly compressed (up to 95% of its volume), resulting in injectable macroporous preformed scaffolds. Hydrogels have been used for therapeutic applications, e.g., as vehicles for in vivo delivery of therapeutic agents, such as small molecules, cells and biologics. Hydrogels are commonly produced from polysaccharides, such as alginates. The polysaccharides may be chemically manipulated to modulate their properties and properties of the resulting hydrogels. The hydrogels of the present invention may be either porous or non-porous. Preferably the compositions of the invention are formed of porous hydrogels. For example, the hydrogels may be nanoporous wherein the diameter of the pores is less than about 10 nm; microporous wherein the diameter of the pores is preferably in the range of about 100 nm-20 µm; or macroporous wherein the diameter of the pores is greater than about 20 µm, more preferably greater than about 100 µm and even more preferably greater than about 400 µm. In certain embodiments, the hydrogel is macroporous with pores of about 50-80 µm in diameter. In certain embodiments, the hydrogel is macroporous with aligned pores of about 400-500 µm in diameter. Methods of preparing porous hydrogel products are known in the art. (See, e.g., U.S. Pat. No.6,511,650, incorporated herein by reference). The hydrogel may be constructed out of a number of different rigid, semi-rigid, flexible, gel, self-assembling, liquid crystalline, or fluid compositions such as peptide polymers, polysaccharides, synthetic polymers, hydrogel materials, ceramics (e.g., calcium phosphate or hydroxyapatite), proteins, glycoproteins, proteoglycans, metals and metal alloys. The compositions are assembled into hydrogels using methods known in the art, e.g., injection molding, lyophilization of preformed structures, printing, self-assembly, phase inversion, solvent casting, melt processing, gas foaming, fiber forming/processing, particulate leaching or a combination thereof. The assembled devices are then implanted or administered to the body of an individual to be treated. The composition comprising a hydrogel may be assembled in vivo in several ways. The hydrogel is made from a gelling material, which is introduced into the body in its ungelled form where it gels in situ. Exemplary methods of delivering components of the composition to a site at which assembly occurs include injection through a needle or other extrusion tool, spraying, painting, or methods of deposit at a tissue site, e.g., delivery using an application device inserted through a cannula. In some embodiments, the ungelled or unformed hydrogel material is mixed with at least one pharmaceutical composition prior to introduction into the body or while it is introduced. The resultant in vivo/in situ assembled device, e.g., hydrogel, contains a mixture of the at least one pharmaceutical composition. In situ assembly of the hydrogel may occur as a result of spontaneous association of polymers or from synergistically or chemically catalyzed polymerization. Synergistic or chemical catalysis is initiated by a number of endogenous factors or conditions at or near the assembly site, e.g., body temperature, ions or pH in the body, or by exogenous factors or conditions supplied by the operator to the assembly site, e.g., photons, heat, electrical, sound, or other radiation directed at the ungelled material after it has been introduced. The energy is directed at the hydrogel material by a radiation beam or through a heat or light conductor, such as a wire or fiber optic cable or an ultrasonic transducer. Alternatively, a shear-thinning material, such as an amphiphile, is used which re-cross links after the shear force exerted upon it, for example by its passage through a needle, has been relieved. In some embodiments, the hydrogel may be assembled ex vivo. In some embodiments, the hydrogel is injectable. For example, the hydrogels are created outside of the body as macroporous scaffolds. Upon injection into the body, the pores collapse causing the gel to become very small and allowing it to fit through a needle. See, e.g., WO2012/149358; and Bencherif et al., 2012, Proc. Natl. Acad. Sci. USA 109.48:19590-5, the content of which are incorporated herein by reference). Suitable hydrogels for both in vivo and ex vivo assembly of hydrogel devices are well known in the art and described, e.g., in Lee et al., 2001, Chem. Rev.7:1869-1879. The peptide amphiphile approach to self-assembly assembly is described, e.g., in Hartgerink et al., 2002, Proc. Natl. Acad. Sci. USA 99:5133-5138. A method for reversible gellation following shear thinning is exemplified in Lee et al., 2003, Adv. Mat.15:1828-1832. In certain embodiments, exemplary hydrogels are comprised of materials that are compatible with encapsulation of materials including polymers, nanoparticles, polypeptides, and cells. Exemplary hydrogels are fabricated from alginate, polyethylene glycol (PEG), PEG-acrylate, agarose, hyaluronic acid, or synthetic protein (e.g., collagen or engineered proteins (i.e., self-assembly peptide-based hydrogels)). For example, a commercially available hydrogel includes BD™ PuraMatrix™. BD™ PuraMatrix™ Peptide Hydrogel is a synthetic matrix that is used to create defined three dimensional (3D) micro-environments for cell culture. In some embodiments, the hydrogel is a biocompatible polymer matrix that is biodegradable in whole or in part. Examples of materials which can form hydrogels include alginates and alginate derivatives, polylactic acid, polyglycolic acid, poly(lactic-co-glycolic acid) (PLGA) polymers, gelatin, collagen, agarose, hyaluronic acid, hyaluronic acid derivative, natural and synthetic polysaccharides, polyamino acids such as polypeptides particularly poly(lysine), polyesters such as polyhydroxybutyrate and poly-epsilon.- caprolactone, polyanhydrides; polyphosphazines, poly(vinyl alcohols), poly(alkylene oxides) particularly poly(ethylene oxides), poly(allylamines)(PAM), poly(acrylates), modified styrene polymers such as poly(4-aminomethylstyrene), pluronic polyols, polyoxamers, poly(uronic acids), poly(vinylpyrrolidone), and copolymers of the above, including graft copolymers. Synthetic polymers and naturally-occurring polymers such as, but not limited to, collagen, fibrin, hyaluronic acid, agarose, and laminin-rich gels may also be used. The term “derivative,” as used herein, refers to a compound that is derived from a similar compound by a chemical reaction. For example, oxidized alginate, which is derived from alginate through oxidization reaction, is a derivative of alginate, The implantable composition can have virtually any regular or irregular shape including, but not limited to, spheroid, cubic, polyhedron, prism, cylinder, rod, disc, or other geometric shape. Accordingly, in some embodiments, the implant is of cylindrical form from about 0.5 to about 10 mm in diameter and from about 0.5 to about 10 cm in length. Preferably, its diameter is from about 1 to about 5 mm and its length from about 1 to about 5 cm. In some embodiments, the compositions of the invention are of spherical form. When the composition is in a spherical form, its diameter can range, in some embodiments, from about 0.5 to about 50 mm in diameter. In some embodiments, a spherical implant’s diameter is from about 5 to about 30 mm. In an exemplary embodiment, the diameter is from about 10 to about 25 mm. In certain embodiments, the scaffold comprises click-hydrogels and/or click-cryogels. A click hydrogel or cryogel is a gel in which cross-linking between hydrogel or cryogel polymers is facilitated by click reactions between the polymers. Each polymer may contain one of more functional groups useful in a click reaction. Given the high level of specificity of the functional group pairs in a click reaction, active compounds can be added to the preformed device prior to or contemporaneously with formation of the hydrogel device by click chemistry. Non-limiting examples of click reactions that may be used to form click- hydrogels include Copper I catalyzed azide-alkyne cycloaddition, strain-promoted assize- alkyne cycloaddition, thiol-ene photocoupling, Diels-Alder reactions, inverse electron demand Diels-Alder reactions, tetrazole-alkene photo-click reactions, oxime reactions, thiol- Michael addition, and aldehyde-hydrazide coupling. Non-limiting aspects of click hydrogels are described in Jiang et al., 2014, Biomaterials, 35:4969-4985, the entire content of which is incorporated herein by reference. In various embodiments, a click alginate is utilized (see, e.g., PCT International Patent Application Publication No. WO 2015/154078 published October 8, 2015, hereby incorporated by reference in its entirety). In certain embodiments, a hydrogel (e.g., cryogel) system can deliver one or more agent (e.g., a growth factor such as BMP-2, and/or a differentiation factor, such as a DLL-4, while creating a space for cells (e.g., stem cells such as hematopoietic stem cells (HSC) infiltration and trafficking). In some embodiments, the hydrogel system according to the present invention delivers BMP-2, which acts as a hematopoietic stem cell (HSC) and/or hematopoietic progenitor cell enhancement/recruitment factor, and DLL-4 as a differentiation factor, which facilitates T cell lineage specification of hematopoietic stem cell and/or hematopoietic progenitor cells. In some embodiments, a cryogel composition, e.g., formed of MA-alginate, can function as a delivering platform by creating a local niche, such as a specific niche for enhancing T-lineage specification. In some embodiments, the cryogel creates a local niche in which the encounter of cells, such as recruited stem cells or progenitor cells, and various exemplary agent of the invention, such as the growth factor and/or differentiation factor can be controlled. In certain embodiments, the cells and the exemplary agents of the present invention are localized into a small volume, and the contacting of the cells and the agents can be quantitatively controlled in space and time. In certain embodiments, the hydrogel (e.g., cryogel) can be engineered to coordinate the delivery of an active agent in space and time, potentially enhancing overall immune modulation performance by adjusting the differentiation and/or specification of recruited cells, such as hematopoietic stem cells or progenitor cells. In certain embodiments, the cells and growth factor/differentiation factor are localized into a small volume, and the delivery of factors in space and time can be quantitatively controlled. As the growth/differentiation factors are released locally, few systemic effects are anticipated, in contrast to systemically delivered agents, such as growth factors. Examples of polymer compositions from which the cryogel or hydrogel is fabricated are described throughout the present disclosure, and include alginate, hyaluronic acid, gelatin, heparin, dextran, carob gum, PEG, PEG derivatives including PEG-co-PGA and PEG-peptide conjugates. The techniques can be applied to any biocompatible polymers, e.g., collagen, chitosan, carboxymethylcellulose, pullulan, polyvinyl alcohol (PVA), Poly(2-hydroxyethyl methacrylate) (PHEMA), Poly(N-isopropylacrylamide) (PNIPAAm), or Poly(acrylic acid) (PAAc). For example, in a particular embodiment, the composition comprises an alginate- based hydrogel/cryogel. In another example, the scaffold comprises a gelatin-based hydrogel/cryogel. Cryogels are a class of materials with a highly porous interconnected structure that are produced using a cryotropic gelation (or cryogelation) technique. Cryogels also have a highly porous structure. Typically, active compounds are added to the cryogel device after the freeze formation of the pore/wall structure of the cryogel. Cryogels are characterized by high porosity, e.g., at least about 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% pores with thin pore walls that are characterized by high density of polymer crosslinking. As used herein, the term “porosity” refers to the percentage of the volume of pores to the volume of the scaffold. It is intended that values and ranges intermediate to the recited values are part of this invention. The walls of cryogels are typically dense and highly cross-linked, enabling them to be compressed through a needle into a subject without permanent deformation or substantial structural damage. In various embodiments, the pore walls comprise at least about 10, 15, 20, 25, 30, 35, or 40% (w/v) polymer. It is intended that values and ranges intermediate to the recited values are part of this invention. In other embodiments, the pore walls comprise about 10-40% polymer. In some embodiments, a polymer concentration of about 0.5-4% (w/v) (before the cryogelation) is used, and the concentration increases substantially upon completion of cryogelation. Non-limiting aspects of cryogel gelation and the increase of polymer concentration after cryogelation are discussed in Beduer et al., 2015 Advanced Healthcare Materials 4.2: 301-312, the entire content of which is incorporated herein by reference. In certain embodiments, cryogelation comprises a technique in which polymerization- crosslinking reactions are conducted in quasi-frozen reaction solution. Non-limiting examples of cryogelation techniques are described in U.S. Patent Application Publication No. 20140227327, published August 14, 2014, the entire content of which is incorporated herein by reference. An advantage of cryogels compared to conventional macroporous hydrogels obtained by phase separation is their high reversible deformability. Cryogels may be extremely soft but can be deformed and reform their shape. In certain embodiments, cryogels can be very tough, can withstand high levels of deformations, such as elongation and torsion and can also be squeezed under mechanical force to drain out their solvent content. The improved deformability properties of alginate cryogels originate from the high crosslinking density of the unfrozen liquid channels of the reaction system. In the cryogelation process, during freezing of the macromonomer (e.g., methacrylated alginate) solution, the macromonomers and initiator system (e.g., APS/TEMED) are expelled from the ice concentrate within the channels between the ice crystals, so that the reactions only take place in these unfrozen liquid channels. After polymerization and, after melting of ice, a porous material is produced whose microstructure is a negative replica of the ice formed. Ice crystals act as porogens. Desired pore size is achieved, in part, by altering the temperature of the cryogelation process. For example, the cryogelation process is typically carried out by quickly freezing the solution at -20 °C. Lowering the temperature to, e.g., -80° C , would result in more ice crystals and lead to smaller pores. In some embodiments, the cryogel is produced by cryo-polymerization of at least methacrylated (MA)-alginate and MA-PEG. In some embodiments, the cryogel is produced by cryo-polymerization of at least MA-alginate, the growth factor, the differentiation factor, and MA-PEG. In some embodiments, the invention also features gelatin scaffolds, e.g., gelatin hydrogels such as gelatin cryogels, which are a cell-responsive platform for biomaterial- based therapy. Gelatin is a mixture of polypeptides that is derived from collagen by partial hydrolysis. These gelatin scaffolds have distinct advantages over other types of scaffolds and hydrogels/cryogels. For example, the gelatin scaffolds of the invention support attachment, proliferation, and survival of cells and are degraded by cells, e.g., by the action of enzymes such as matrix metalloproteinases (MMPs) (e.g., recombinant matrix metalloproteinase-2 and -9). In certain embodiments, prefabricated gelatin cryogels rapidly reassume their approximately original shape ("shape memory") when injected subcutaneously into a subject (e.g., a mammal such as a human, dog, cat, pig, or horse) and elicit little or no harmful host immune response (e.g., immune rejection) following injection. In some embodiments, the hydrogel (e.g., cryogel) comprises polymers that are modified, e.g., sites on the polymer molecule are modified with a methacrylic acid group (methacrylate (MA)) or an acrylic acid group (acrylate). Exemplary modified hydrogels/cryogels are MA- alginate (methacrylated alginate) or MA-gelatin. In the case of MA-alginate or MA-gelatin, 50% corresponds to the degree of methacrylation of alginate or gelatin. This means that every other repeat unit contains a methacrylated group. The degree of methacrylation can be varied from about 1% to about 100%. Preferably, the degree of methacrylation varies from about 1% to about 90%. In certain embodiments, polymers can also be modified with acrylated groups instead of methacrylated groups. The product would then be referred to as an acrylated-polymer. The degree of methacrylation (or acrylation) can be varied for most polymers. However, some polymers (e.g., PEG) maintain their water-solubility properties even at 100% chemical modification. After crosslinking, polymers normally reach near complete methacrylate group conversion indicating approximately 100% of cross-linking efficiency. As used herein, the term “cross-linking efficiency” refers to the percentage of macromonomers that are covalently linked. For example, the polymers in the hydrogel are 50-100% crosslinked (covalent bonds). The extent of crosslinking correlates with the durability of the hydrogel. Thus, a high level of crosslinking (90-100%) of the modified polymers is desirable. For example, the highly crosslinked hydrogel/cryogel polymer composition is characterized by at least about 50% polymer crosslinking (e.g., about 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100%; it is intended that values and ranges intermediate to the recited values are part of this invention.). The high level of crosslinking confers mechanical robustness to the structure. Preferably, the percentage of crosslinking is less than about 100%. The composition is formed using a free radical polymerization process and a cryogelation process. For example, the cryogel is formed by cryopolymerization of methacrylated gelatin, methacrylated alginate, or methacrylated hyaluronic acid. In some embodiments, the cryogel comprises a methacrylated gelatin macro monomer or a methacrylated alginate macromonomer at concentration of about 1.5% (w/v) or less (e.g., about 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2% or less; it is intended that values and ranges intermediate to the recited values are part of this invention.). In some embodiments, the methacrylated gelatin or alginate macromonomer concentration is about 1% (w/v). In certain embodiments, the cryogel comprises at least about 75% (v/v) pores, e.g., about 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% (v/v) or more pores. It is intended that values and ranges intermediate to the recited values are part of this invention. In some embodiments, the pores are interconnected. Interconnectivity is important to the function of the hydrogel and/or cryogel, as without interconnectivity, water would become trapped within the gel. Interconnectivity of the pores permits passage of water (and other compositions such as cells and compounds) in and out of the structure. In certain embodiments, in a fully hydrated state, the hydrogel (e.g., cryogel) comprises at least about 90% water (volume of water / volume of the scaffold) (e.g., between about 90-99%, at least about 92%, 95%, 97%, 99%, or more). For example, at least about 90% (e.g., at least about 92%, 95%, 97%, 99%, or more) of the volume of the cryogel is made of liquid (e.g., water) contained in the pores. It is intended that values and ranges intermediate to the recited values are part of this invention. In certain embodiments, in a compressed or dehydrated hydrogel, up to about 50%, 60%, 70% of that water is absent, e.g., the cryogel comprises less than about 25% (e.g., about 20%, 15%, 10%, 5% or less) water. In certain embodiments, the cryogels of the invention comprise pores large enough for a cell to travel through. For example, the cryogel contains pores of about 20-500 µm in diameter, e.g., about 20-30µm, about 30-150µm, about 50-500 µm, about 50-450 µm, about 100-400 µm, about 200-500 µm. In some embodiments, the hydrated pore size is about 1- 500 µm (e.g., about 10-400 µm, about 20-300 µm, about 50-250 µm). In certain embodiments, the cryogel contains pores about 50-80 µm in diameter. In some embodiments, injectable hydrogels or cryogels are further functionalized by addition of a functional group selected from the group consisting of: amino, vinyl, aldehyde, thiol, silane, carboxyl, azide, or alkyne. Alternatively or in addition, the cryogel is further functionalized by the addition of a further cross-linker agent (e.g., multiple arms polymers, salts, aldehydes, etc.). The solvent can be aqueous, and in particular, acidic or alkaline. The aqueous solvent can comprise a water-miscible solvent (e.g., methanol, ethanol, DMF, DMSO, acetone, dioxane, etc). For cryogels, the cryo-crosslinking may take place in a mold and the cryogels (which may be injected) can be degradable. The pore size can be controlled by the selection of the main solvent used, the incorporation of a porogen, the freezing temperature and rate applied, the crosslinking conditions (e.g. polymer concentration), and also the type and molecule weight of the polymer used. The shape of the cryogel may be dictated by a mold and can thus take on any shape desired by the fabricator, e.g., various sizes and shapes (disc, cylinders, squares, strings, etc.) are prepared by cryogenic polymerization. Injectable cryogels can be prepared in the micrometer-scale to centimeter-scale. Exemplary volumes vary from a few hundred µm³ (e.g., about 100-500 µm³) to about 10 cm³. In certain embodiment, an exemplary scaffold composition is between about 100 µm³ to 100 mm³ in size. In various embodiments, the scaffold is between about 10 mm³ to about 100 mm³ in size. In certain embodiments, the scaffold is about 30 mm³ in size. In some embodiments, the cryogels are hydrated, loaded with compounds and loaded into a syringe or other delivery apparatus. For example, the syringes are prefilled and refrigerated until use. In another example, the cryogel is dehydrated, e.g., lyophilized, optionally with a compound (such as a growth factor or differentiation factor) loaded in the gel and stored dry or refrigerated. Prior to administration, a cryogel-loaded syringe or apparatus may be contacted with a solution containing compounds to be delivered. For example, the barrel of the cryogel pre-loaded syringe is filled with a physiologically- compatible solution, e.g., phosphate-buffered saline (PBS). Alternatively, the cryogel may be administered to a desired anatomical site followed by administration of the physiologically- compatible solution, optionally containing other ingredients, e.g., a growth factor and/or a differentiation factor or together with one or more compounds disclosed herein. The cryogel is then rehydrated and regains its shape integrity in situ. In certain embodiments, the volume of PBS or other physiologic solution administered following cryogel placement is generally about 10 times the volume of the cryogel itself. The cryogel also has the advantage that, upon compression, the cryogel composition maintains structural integrity and shape memory properties. For example, the cryogel is injectable through a hollow needle. For example, the cryogel returns to its approximately original geometry after traveling through a needle (e.g., a 16 gauge (G) needle, e.g., having a 1.65 mm inner diameter). Other exemplary needle sizes are 16-gauge, an 18-gauge, a 20- gauge, a 22- gauge, a 24-gauge, a 26-gauge, a 28-gauge, a 30-gauge, a 32-gauge, or a 34- gauge needle. Injectable cryogels have been designed to pass through a hollow structure, e.g., very fine needles, such as 18-30 G needles. In certain embodiments, the cryogel returns to its approximately original geometry after traveling through a needle in a short period of time, such as less than about 10 seconds, less than about 5 seconds, less than about 2 seconds, or less than about 1 second. The cryogels may be injected to a subject using any suitable injection device. For example, the cryogels may be injected using syringe through a needle. A syringe may include a plunger, a needle, and a reservoir that comprises compositions of the present invention. The injectable cryogels may also be injected to a subject using a catheter, a cannula, or a stent. The injectable cryogels may be molded to a desired shape, in the form of rods, square, disc, spheres, cubes, fibers, foams. In some cases, the cryogel is in the shape of a disc, cylinder, square, rectangle, or string. For example, the cryogel composition is between about 100 µm³ to 10 cm³ in size, e.g., between 10 mm³ to 100 mm³ in size. For example, the cryogel composition is between about 1 mm in diameter to about 50 mm in diameter (e.g., about 5 mm). Optionally, the thickness of the cryogel is between about 0.2 mm to about 50 mm (e.g., about 2 mm). Three exemplary cryogel materials systems are described below. a) Methacrylated gelatin cryogel (CryoGeIMA) - An exemplary cryogel utilized methacrylated gelatin and the results are described in detail in U.S. Patent Application Publication No.2014-0227327, published August 14, 2014, the entire contents of which are incorporated herein by reference. b) Methacrylated alginate cryogel (CryoMAAlginate) - An exemplary cryogel utilized methacrylated alginate and the results are described in detail in U.S. Patent Application Publication No.2014-0227327, published August 14, 2014, the entire contents of which are incorporated herein by reference. c) Click Alginate cryogel with Laponite nanoplatelets (CryoClick) - The base material is click alginate (PCT International Patent Application Publication No. WO 2015/154078 published October 8, 2015, hereby incorporated by reference in its entirety). In some examples, the base material contains laponite (commercially available silicate clay used in many consumer products such as cosmetics). Laponite has a large surface area and highly negative charge density which allows it to adsorb positively charged moieties on a variety of proteins and other biologically active molecules by an electrostatic interaction, thereby allowing drug loading. When placed in an environment with a low concentration of drug, adsorbed drug releases from the laponite in a sustained manner. This system allows release of a more flexible array of various agents, e.g., growth factors, compared to the base material alone. Various embodiments of the present subject matter include delivery vehicles comprising a pore-forming scaffold composition. For example, pores (such as macropores) are formed in situ within a hydrogel following hydrogel injection into a subject. Pores that are formed in situ via degradation of a sacrificial porogen hydrogel within the surrounding hydrogel (bulk hydrogel) facilitate recruitment and trafficking of cells, as well as the release of any composition or agent of the present invention, for example, a growth factor, such as BMP-2, a differentiation factor , or a homing factor, or any combination thereof. In some embodiments, the sacrificial porogen hydrogel, the bulk hydrogel, or both the sacrificial porogen hydrogel and the bulk hydrogel may comprise any composition or agent of the present invention, for example, a growth factor, a differentiation factor, and/or, a homing factor, or any combination thereof. In various embodiments, the pore-forming composition becomes macroporous over time when resident in the body of a recipient animal such as a mammalian subject. For example, the pore-forming composition may comprise a sacrificial porogen hydrogel and a bulk hydrogel, wherein the sacrificial porogen hydrogel degrades at least about 10% faster (e.g., at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% faster) than the bulk hydrogel. It is intended that values and ranges intermediate to the recited values are part of this invention. The sacrificial porogen hydrogel may degrade leaving macropores in its place. In certain embodiments, the macropores are open interconnected macropores. In some embodiments, the sacrificial porogen hydrogel may degrade more rapidly than the bulk hydrogel, because the sacrificial porogen hydrogel (i) is more soluble in water (comprises a lower solubility index), (ii) is cross-linked to protease-mediated degradation motifs as described in U.S. Patent Application Publication No.2005-0119762, published June 2, 2005 (incorporated herein by reference in its entirety), (iii) comprises a shorter polymer that degrades more quickly compared to that of a longer bulk hydrogel polymer, (iv) is modified to render it more hydrolytically degradable than the bulk hydrogel (e.g., by oxidation), and/or (v) is more enzymatically degradable compared to the bulk hydrogel. In various embodiments, a scaffold is loaded (e.g., soaked with) with one or more active compounds after polymerization. In certain embodiments, device or scaffold polymer forming material is mixed with one or more active compounds before polymerization. In some embodiments, a device or scaffold polymer forming material is mixed with one or more active compounds before polymerization, and then is loaded with more of the same or one or more additional active compounds after polymerization. In some embodiments, pore size or total pore volume of a composition or scaffold is selected to influence the release of compounds from the device or scaffold. Exemplary porosities (e.g., nanoporous, microporous, and macroporous scaffolds and devices) and total pore volumes (e.g., about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95% or more of the volume of the scaffold) are described herein. It is intended that values and ranges intermediate to the recited values are part of this invention. Increased pore size and total pore volume increases the amount of compounds that can be delivered into or near a tissue, such as bone marrow. In some embodiments, a pore size or total pore volume is selected to increase the speed at which active ingredients exit the composition or scaffold. In various embodiments, an active ingredient may be incorporated into the scaffold material of a hydrogel or cryogel, e.g., to achieve continuous release of the active ingredient from the scaffold or device over a longer period of time compared to active ingredient that may diffuse from a pore cavity. Porosity influences recruitment of the cells into devices and scaffolds and the release of substances from devices and scaffolds. Pores may be, e.g., nanoporous, microporous, or macroporous. For example, the diameter of nanopores is less than about 10 nm. Micropores are in the range of about 100 nm to about 20 µm in diameter. Macropores are greater than about 20 µm (e.g., greater than about 100 µm or greater than about 400 µm) in diameter. Exemplary macropore sizes include about 50 µm, about 100 µm, about 150 µm, about 200 µm, about 250 µm, about 300 µm, about 350 µm, about 400 µm, about 450 µm, about 500 µm, about 550 µm, and about 600 µm in diameter. It is intended that values and ranges intermediate to the recited values are part of this invention. Macropores are those of a size that permit a eukaryotic cell to traverse into or out of the composition. In one example, a macroporous composition has pores of about 400 µm to about 500 µm in diameter. The preferred pore size depends on the application. In certain embodiments, the pores have a diameter of about 50 µm to about 80 µm. In various embodiments, the composition is manufactured in one stage in which one layer or compartment is made and infused or coated with one or more compounds. Exemplary bioactive compositions comprise polypeptides or polynucleotides. In certain embodiments, the composition is manufactured in two or more (e.g., 3, 4, 5, 6, 7, 8, 9, 10 or more) stages in which one layer or compartment is made and infused or coated with one or more compounds followed by the construction of second, third, fourth or more layers, which are in turn infused or coated with one or more compounds in sequence. In some embodiments, each layer or compartment is identical to the others or distinguished from one another by the number or mixture of bioactive compositions as well as distinct chemical, physical and biological properties. Polymers may be formulated for specific applications by controlling the molecular weight, rate of degradation, and method of scaffold formation. Coupling reactions can be used to covalently attach bioactive agent, such as the differentiation factor to the polymer backbone. In some embodiments, one or more compounds is added to the scaffold compositions using a known method including surface absorption, physical immobilization, e.g., using a phase change to entrap the substance in the scaffold material. For example, a growth factor is mixed with the scaffold composition while it is in an aqueous or liquid phase, and after a change in environmental conditions (e.g., pH, temperature, ion concentration), the liquid gels or solidifies thereby entrapping the bioactive substance. In some embodiments, covalent coupling, e.g., using alkylating or acylating agents, is used to provide a stable, long term presentation of a compound on the scaffold in a defined conformation. Exemplary reagents for covalent coupling of such substances are provided in the table below. Table 1: Methods to Covalently Couple Peptides/Proteins to Polymers

[a] EDC: l-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride; DCC: dicyclohexylcarbodiimide Hyaluronic Acid In certain embodiments, the composition of the present invention comprises a hyaluronic acid hydrogel or cryogel. Hyaluronic acid (HA; conjugate base hyaluronate), is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. One of the chief components of the extracellular matrix, hyaluronic acid contributes significantly to cell proliferation and migration. Natural hyaluronic acid is an important component of articular cartilage, muscular connective tissues, and skin. Hyaluronic acid is a polymer of disaccharides, composed of D-glucuronic acid and N- acetyl-D-glucosamine, linked via alternating β-(1→4) and β-(1→3) glycosidic bonds. Hyaluronic acid can be 25,000 disaccharide repeats in length. Polymers of hyaluronic acid can range in size from 5,000 to 20,000,000 Da. Hyaluronic acid can also contain silicon. Hyaluronic acid is energetically stable, in part because of the stereochemistry of its component disaccharides. Bulky groups on each sugar molecule are in sterically favored positions, whereas the smaller hydrogens assume the less-favorable axial positions. Hyaluronic acid can be degraded by a family of enzymes called hyaluronidases, which are present in many mammals, e.g., a human. Hyaluronic acid can also be degraded via non-enzymatic reactions. These include acidic and alkaline hydrolysis, ultrasonic disintegration, thermal decomposition, and degradation by oxidants. Due to its high biocompatibility and its common presence in the extracellular matrix of tissues, hyaluronic acid is used to form hydrogels, e.g., cryogels, as a biomaterial scaffold in tissue engineering research. Hyaluronic acid hydrogels are formed through crosslinking. Hyaluronic acid can form a hydrogel, e.g., cryogel, into a desired shape to deliver therapeutic molecules into a host. Hyaluronic acids, for use in the present compositions, can be crosslinked by attaching thiols, methacrylates, hexadecylamides, and tyramines. Hyaluronic acids can also be crosslinked directly with formaldehyde or with divinylsulfone. The term “hyaluronic acid,” includes unmodified hyaluronic acid or modified hyaluronic acid. Modified hyaluronic acid includes, but is not limited to, oxidized hyaluronic acid and/or reduced hyaluronic acid. The term “hyaluronic acid” or “hyaluronic acid polymers” may also include hyaluronic acid, e.g., unmodified hyaluronic acid, oxidized hyaluronic acid or reduced hyaluronic acid, or methacrylated hyaluronic acid or acrylated hyaluronic acid. Hyaluronic acid may also refer to any number of derivatives of hyaluronic acid. Alginate Scaffolds In certain embodiments, the composition of the invention comprises an alginate hydrogel. Alginates are versatile polysaccharide based polymers that may be formulated for specific applications by controlling the molecular weight, rate of degradation and method of scaffold formation. Alginate polymers are comprised of two different monomeric units, (1- 4)-linked β-D-mannuronic acid (M units) and α L-guluronic acid (G units) monomers, which can vary in proportion and sequential distribution along the polymer chain. Alginate polymers are polyelectrolyte systems which have a strong affinity for divalent cations (e.g., Ca⁺², Mg⁺², Ba⁺²) and form stable hydrogels when exposed to these molecules. See Martinsen A., et al., 1989, Biotech. & Bioeng., 33: 79-89). For example, calcium cross- linked alginate hydrogels are useful for dental applications, wound dressings chondrocyte transplantation and as a matrix for other cell types. Without wishing to be bound by theory, it is believed that G units are preferentially crosslinked using calcium crosslinking, whereas click reaction based crosslinking is more indiscriminate with respect to G units or M units (i.e., both G and M units can be crosslinked by click chemistry). Alginate scaffolds and the methods for making them are known in the art. See, e.g., International Patent Application Publication No. WO2017/075055 A1, published on May 4, 2017, the entire contents of which are incorporated herein by reference. The alginate polymers useful in the context of the present invention can have an average molecular weight from about 20 kDa to about 500 kDa, e.g., from about 20 kDa to about 40 kDa, from about 30 kDa to about 70 kDa, from about 50 kDa to about 150 kDa, from about 130 kDa to about 300 kDa, from about 230 kDa to about 400 kDa, from about 300 kDa to about 450 kDa, or from about 320 kDa to about 500 kDa. In one example, the alginate polymers useful in the present invention may have an average molecular weight of about 32 kDa. In another example, the alginate polymers useful in the present invention may have an average molecular weight of about 265 kDa. In some embodiments, the alginate polymer has a molecular weight of less than about 1000 kDa, e.g., less than about 900 KDa, less than about 800 kDa, less than about 700 kDa, less than about 600 kDa, less than about 500 kDa, less than about 400 kDa, less than about 300 kDa, less than about 200 kDa, less than about 100 kDa, less than about 50 kDa, less than about 40 kDa, less than about 30 kDa or less than about 25 kDa. In some embodiments, the alginate polymer has a molecular weight of about 1000 kDa, e.g., about 900 kDa, about 800 kDa, about 700 kDa, about 600 kDa, about 500 kDa, about 400 kDa, about 300 kDa, about 200 kDa, about 100 kDa, about 50 kDa, about 40 kDa, about 30 kDa or about 25 kDa. In one embodiment, the molecular weight of the alginate polymers is about 20 kDa. Coupling reactions can be used to covalently attach bioactive agent, such as an atom, a chemical group, a nucleoside, a nucleotide, a nucleobase, a sugar, a nucleic acid, an amino acid, a peptide, a polypeptide, a protein, or a protein complex, to the polymer backbone. The term “alginate”, used interchangeably with the term “alginate polymers”, includes unmodified alginate or modified alginate. Modified alginate includes, but not limited to, oxidized alginate (e.g., comprising one or more algoxalate monomer units) and/or reduced alginate (e.g., comprising one or more algoxinol monomer units). In some embodiments, oxidized alginate comprises alginate comprising one or more aldehyde groups, or alginate comprising one or more carboxylate groups. In other embodiments, oxidized alginate comprises highly oxidized alginate, e.g., comprising one or more algoxalate units. Oxidized alginate may also comprise a relatively small number of aldehyde groups (e.g., less than 15%, e.g., 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1% aldehyde groups or oxidation on a molar basis). It is intended that values and ranges intermediate to the recited values are part of this invention. The term “alginate” or “alginate polymers” may also include alginate, e.g., unmodified alginate, oxidized alginate or reduced alginate, or methacrylated alginate or acrylated alginate. Alginate may also refer to any number of derivatives of alginic acid (e.g., calcium, sodium or potassium salts, or propylene glycol alginate ). See, e.g., WO1998012228A1, hereby incorporated by reference. Porous and Pore-forming Scaffolds The scaffolds of the present invention may be nonporous or porous. In certain embodiments, the scaffolds of the present invention are porous. Porosity of the scaffold composition influences migration of the cells through the device. Pores may be nanoporous, microporous, or macroporous. For example, the diameter of nanopores is less than about 10 nm. Micropores are in the range of about 100 nm to about 20 µm in diameter. Macropores are greater than about 20 µm (e.g., greater than about 100 µm or greater than about 400 µm) in diameter. Exemplary macropore sizes include about 50 µm, 100 µm, 150 µm, 200 µm, 250 µm, 300 µm, 350 µm, 400 µm, 450 µm, 500 µm, 550 µm, and 600 µm in diameter. It is intended that values and ranges intermediate to the recited values are part of this invention. Macropores are of a size that permits a eukaryotic cell to traverse into or out of the composition. In certain embodiments, a macroporous composition has pores of about 400 µm to 500 µm in diameter. The size of pores may be adjusted for different purpose. For example, for cell recruitment and cell release, the pore diameter may be greater than 50 µm. In certain embodiments, a macroporous composition has pores of about 50 µm – about 80 µm in diameter. In some embodiments, the scaffolds contain pores before the administration into a subject. In some embodiments, the scaffolds comprise a pore-forming scaffold composition. Pore-forming scaffolds and the methods for making pore-forming scaffolds are known in the art. See, e.g., U.S. Patent Publication US2014/0079752A1, the content of which is incorporated herein by reference. In certain embodiments, the pore-forming scaffolds are not initially porous, but become macroporous over time resident in the body of a recipient animal such as a mammalian subject. In certain embodiments, the pore-forming scaffolds are hydrogel scaffolds. The pore may be formed at different time, e.g., after about 12 hours, or 1, 3, 5, 7, or 10 days or more after administration, i.e., resident in the body of the subject. In certain embodiments, the pore-forming scaffolds comprise a first hydrogel and a second hydrogel, wherein the first hydrogel degrades at least about 10% faster (e.g., at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50% faster, at least about 2 times faster, or at least about 5 times faster) than the second hydrogel. It is intended that values and ranges intermediate to the recited values are part of this invention. In certain embodiments, the first hydrogel comprises a porogen that degrades leaving a pore in its place. For example, the first hydrogel is a porogen and the resulting pore after degradation in situ is within 25% of the size of the initial porogen, e.g., within 20%, within 15%, or within 10% of the size of the initial porogen. Preferably, the resulting pore is within 5% of the size of the initial porogen. It is intended that values and ranges intermediate to the recited values are part of this invention. The first hydrogel may degrade faster than the second hydrogel due to the difference in their physical, chemical, and/or biological properties. In certain embodiments, the first hydrogel degrades more rapidly than the second hydrogel, because the first hydrogel is more soluble in water (comprises a lower solubility index). In certain embodiments, the first hydrogel degrades more rapidly because it is cross-linked to protease-mediated degradation motifs as described in U.S. Patent Publication US2005/0119762A1, the content of which is incorporated herein by reference. In certain embodiments, the molecular mass of the polymers used to form the first hydrogel composition (a porogen) is approximately 50 kilodaltons (kDa), and the molecular mass of the polymers used to form the second hydrogel composition (bulk) is approximately 250 kDa. A shorter polymer (e.g., that of a porogen) degrades more quickly compared to that of a longer polymer (e.g., that of the bulk composition). In certain embodiments, a composition is modified to render it more hydrolytically degradable by virtue of the presence of sugar groups (e.g., approximately 3-10% sugar of an alginate composition). In certain embodiments, the porogen hydrogel is chemically modified, such as oxidized, to render it more susceptible to degradation. In some embodiments, the porogen hydrogel is more enzymatically degradable compared to the bulk hydrogel. The composite (first and second hydrogel) composition is permeable to bodily fluids, e.g., containing an enzyme which is exposed to the composition and degrades the porogen hydrogel. In some embodiments, the second hydrogel is cross-linked around the first hydrogel, i.e., the porogens (first hydrogel) are completely physically entrapped in the bulk (second) hydrogel. The click reagents disclosed herein can be provided in the bulk hydrogel or the porogen hydrogel. In exemplary embodiments, the click reagents, e.g., polymers or nanoparticles, are provided in the bulk hydrogel. In certain embodiments, hydrogel micro-beads (“porogens”) are formed. Porogens are encapsulated into a “bulk” hydrogel that is either non-degradable or which degrades at a slower rate compared to the porogens. Immediately after hydrogel formation, or injection into the desired site in vivo, the composite material lacks pores. Subsequently, porogen degradation causes pores to form in situ. The size and distribution of pores are controlled during porogen formation, and mixing with the polymers which form the bulk hydrogel. In some embodiments, the polymer utilized in the pore-forming scaffolds is naturally- occurring or synthetically made. In one example, both the porogens and bulk hydrogels are formed from alginate. In certain embodiments, the alginate polymers suitable for porogen formation have a molecular weight from 5,000 to 500,000 Daltons. The polymers are optionally further modified (e.g., by oxidation with sodium periodate, (Bouhadir et al., 2001, Biotech. Prog. 17:945-950, hereby incorporated by reference), to facilitate rapid degradation. In certain embodiments, the polymers are crosslinked by extrusion through a nebulizer with co-axial airflow into a bath of divalent cation (for example, Ca²⁺ or Ba²⁺) to form hydrogel micro- beads. Higher airflow rate leads to lower the porogen diameter. In some embodiments, the porogen hydrogel microbeads contain oxidized alginate. For example, the porogen hydrogel can contain about 1-50% (w/v) oxidized alginate. In exemplary embodiments, the porogen hydrogel can contain about 1-10% oxidized alginate. In one embodiment, the porogen hydrogel contains about 7.5% oxidized alginate. In certain embodiments, the concentration of divalent ions used to form porogens may vary from about 5 to about 500 mM, and the concentration of polymer from about 1% to about 5% by weight/volume. However, any method which produces porogens that are significantly smaller than the bulk phase is suitable. Porogen chemistry can further be manipulated to produce porogens that interact with host proteins and/or cells, or inhibit interactions with host proteins and/or cells. The alginate polymers suitable for formation of the bulk hydrogel have a molecular weight from about 5,000 to about 500,000 Da. The polymers may be further modified (for example, by oxidation with sodium periodate), to facilitate degradation, as long as the bulk hydrogel degrades more slowly than the porogen. The polymers may also be modified to present biological cues to control cell responses (e.g., integrin binding adhesion peptides such as RGD). Either the porogens or the bulk hydrogel may also encapsulate bioactive factors such as oligonucleotides, growth factors or drugs to further control cell responses. The concentration of divalent ions used to form the bulk hydrogel may vary from about 5 to about 500 mM, and the concentration of polymer from about 1% to about 5% by weight/volume. The elastic modulus of the bulk polymer is tailored for its purpose, e.g., to recruit stem cells or progenitor cells. Methods relevant to generating the hydrogels described herein include the following. Bouhadir et al., 1999, Polymer, 40: 3575-84 (incorporated herein by reference in its entirety) describes the oxidation of alginate with sodium periodate, and characterizes the reaction. Bouhadir et al., 2001, Biotechnol. Prog., 17: 945-50 (incorporated herein by reference in its entirety) describes oxidation of high molecular weight alginate to form alginate dialdehyde (alginate dialdehyde is high molecular weight (M_w) alginate in which a certain percent, e.g., 5%, of sugars in alginate are oxidized to form aldehydes), and application to make hydrogels degrade rapidly. Kong et al., 2002, Polymer, 43: 6239-46 (incorporated herein by reference in its entirety) describes the use of gamma-irradiation to reduce the weight-averaged molecular weight (M_w) of guluronic acid (GA) rich alginates without substantially reducing GA content (e.g., the gamma irradiation selectively attacks mannuronic acid, MA blocks of alginate). Alginate is comprised of GA blocks and MA blocks, and it is the GA blocks that give alginate its rigidity (elastic modulus). Kong et al., 2002, Polymer, 43: 6239-46 (incorporated herein by reference in its entirety) shows that binary combinations of high Mw, GA rich alginate with irradiated, low Mw, high GA alginate crosslinks with calcium to form rigid hydrogels, but which degrade more rapidly and also have lower solution viscosity than hydrogels made from the same overall weight concentration of only high Mw, GA rich alginate. Alsberg et al., 2003, J Dent Res, 82(11): 903-8 (incorporated herein by reference in its entirety) describes degradation profiles of hydrogels made from irradiated, low Mw, GA- rich alginate, with application in bone tissue engineering. Kong et al., 2004, Adv. Mater, 16(21): 1917-21 (incorporated herein by reference) describes control of hydrogel degradation profile by combining gamma irradiation procedure with oxidation reaction, and application to cartilage engineering. Techniques to control degradation of hydrogen biomaterials are well known in the art. For example, Lutolf MP et al., 2003, Nat Biotechnol., 21: 513-8 (incorporated herein by reference in its entirety) describes poly(ethylene glycol) based materials engineered to degrade via mammalian enzymes (MMPs). Bryant SJ et al., 2007, Biomaterials, 28(19): 2978-86 (US 7,192,693 B2; incorporated herein by reference in its entirety) describes a method to produce hydrogels with macro-scale pores. A pore template (e.g., poly- methylmethacrylate beads) is encapsulated within a bulk hydrogel, and then acetone and methanol are used to extract the porogen while leaving the bulk hydrogel intact. Silva et al., 2008, Proc. Natl. Acad. Sci USA, 105(38): 14347-52 (incorporated herein by reference in its entirety; US 2008/0044900) describes deployment of endothelial progenitor cells from alginate sponges. The sponges are made by forming alginate hydrogels and then freeze- drying them (ice crystals form the pores). Ali et al., 2009, Nat Mater (incorporated herein by reference in its entirety) describes the use of porous scaffolds to recruit dendritic cells and program them to elicit anti-tumor responses. Huebsch et al., 2010, Nat Mater, 9: 518-26 (incorporated herein by reference in its entirety) describes the use of hydrogel elastic modulus to control the differentiation of encapsulated mesenchymal stem cells. In some embodiments, the scaffold composition comprises open interconnected macropores. Alternatively or in addition, the scaffold composition comprises a pore-forming scaffold composition. In certain embodiments, the pore-forming scaffold composition may comprise a sacrificial porogen hydrogel and a bulk hydrogel, wherein the pore-forming scaffold composition lacks macropores. For example, the sacrificial porogen hydrogel may degrade at least 10% faster than the bulk hydrogel leaving macropores in its place following administration of said pore-forming scaffold into a subject. In some embodiments, the sacrificial porogen hydrogel is in the form of porogens that degrade to form said macropores. For example, the macropores may comprise pores having a diameter of, e.g., about 10-400 μm. ACTIVE AGENTS The compositions of the present invention can comprise an active agent. The term “active agent,” as used herein, refers to an agent that is capable of modulating the activity of an innate leukocyte, restoring levels of functional innate leukocytes, reconstituting levels of functional innate leukocytes, enhancing the regeneration of functional innate leukocytes, enhancing immunity, and/or treating or preventing a disease or disorder in a subject, such as a disorder that is caused by or associated with a deficiency in functional innate leukocytes. In certain embodiments, the active agent comprises an amino acid, a peptide, a protein, a nucleic acid, an oligonucleotide, a small molecule, or a combination thereof. In certain embodiments, the active agent comprises a protein, optionally, wherein the protein is an isolated protein and/or a recombinant protein. In certain embodiments, the active agent comprises a cytokine, a chemokine, and/or a growth factor. In certain embodiments, the active agent comprises a cytokine, optionally, a pro-inflammatory cytokine and/or an anti- inflammatory cytokine. In certain embodiments, the active agent is selected from the group consisting of a granulocyte colony stimulating factor (G-CSF), a granulocyte-macrophage colony- stimulating factor (GM-CSF), a bone morphogenetic protein 2 (BMP2), a stromal cell- derived factor (SDF), a platelet activating factor (PAF), a tumor necrosis factor α (TNFα), an interleukin-1 (IL-1), an interleukin-1α (IL-1α), an interleukin-1β (IL-1β), an interleukin-2 (IL-2), an interleukin-3 (IL-3), an interleukin-4 (IL-4), an interleukin-5 (IL-5), an interleukin- 6 (IL-6), an interleukin-7 (IL-7), an interleukin-8 (IL-8), an interleukin-9 (IL-9), an interleukin-10 (IL-10), an interleukin-11 (IL-11), an interleukin-12 (IL-12), an interleukin-13 (IL-13), an interleukin-14 (IL-14), an interleukin-15 (IL-15), an interleukin-16 (IL-16), an interleukin-17 (IL-17), an interleukin-18 (IL-18), an interleukin-19 (IL-19), an interleukin-20 (IL-20), an interleukin-21 (IL-21), an interleukin-22 (IL-22), an interleukin-23 (IL-23), an interleukin-24 (IL-24), an interleukin-25 (IL-25), an interleukin-26 (IL-26), an interleukin-27 (IL-27), an interleukin-28 (IL-28), an interleukin-29 (IL-29), an interleukin-30 (IL-30), an interleukin-31 (IL-31), an interleukin-32 (IL-32), an interleukin-33 (IL-33), an interleukin-34 (IL-34), an interleukin-35 (IL-35), an interleukin-36 (IL-36), an interleukin-1 receptor antagonist (IL-1Ra), a growth-related gene product-α (GRO-α), a growth-related gene product-β (GRO-β), a macrophage infiltrating protein-1α (MCP-1α), a macrophage infiltrating protein-1β (MCP-1β), a cytokine-induced chemoattractant (CINC), an interferon- α (IFN-α), an interferon-β (IFN-β), an interferon-γ (IFN-γ), a Fas ligand (FasL), a CD30 ligand (CD30L), a vascular endothelial growth factor (VEGF), a hepatocyte frowth factor (HGF), a transforming growth factor alpha (TGF-α), an oncostain (OSM), a neurotrophin, a monocyte chemoattractant protein-1 (MCP-1), a stem cell factor (SCF), a complement 5a (C5a), and an erythropoietin (EPO). In certain embodiments, the active agent comprises a G-CSF. In certain embodiments, the active agent comprises a polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF). In certain embodiments, the active agent is G-CSF. In certain embodiments, the inclusion of such active agents in the compositions of the present invention promotes the infiltration of functional innate leukocytes, e.g., neutrophils, to the scaffold composition administered to the subject. In certain embodiments, the active agents are encapsulated in the material. In certain embodiments, the active agents are released from the material over an extended period of time (e.g., about 7-30 days or longer, about 17- 18 days). In some embodiments, the degradation profile of the scaffold compositions, described herein, comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, is responsive to functional innate leukocyte recovery. Without wishing to be bound by theory, immune deficiency and/or the level of functional innate leukocytes, including the level of activated neutrophils, in a subject can impact the rate of degradation of the scaffold compositions and the release of encapsulated active agent. In particular, the immune-responsiveness of the scaffold compositions, described herein, can facilitate the controlled, sustained, and/or delayed release of an encapsulated active agent, such as G-CSF. In certain embodiments, the active agents retain their bioactivity over an extended period of time. The bioactivity of the active agent may be measured by any appropriate means. In certain example, the active agents retain at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99% or more of their bioactivity for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days at least 20 days, or at least 30 days after the incorporation of the active agent into the scaffold. In certain embodiments, the active agent may be present at between about 0.001 nmol and about 1000 nmol per scaffold, or about 0.001 and about 100 nmol per scaffold, or about 0.001 nmol and about 1 nmol per scaffold. In some embodiments, the active agent may be present at between about 1 ng to 1000 micrograms per scaffold. For example, the active agent may be present at an amount between about 1 µg and about 1000 µg, between about 1 µg and 500 µg, between about 1 µg and about 200 µg, between about 1 µg and about 100 µg, between about 1 µg and about 50 µg, or between about 1 µg and 10 µg. In certain embodiments, the composition of the present invention comprises nanogram quantities of active agent (e.g., about 1 ng to about 1000 ng of active agent). For example, the active agent may be present at an amount between about 5 ng and about 500 ng, between about 5 ng and about 250 ng, between about 5 ng and about 200 ng, between about 10 ng and about 200 ng, between about 25 ng and about 200 ng, between about 50 ng and 200 ng, between about 100 ng and 200 ng, and about 200 ng. Nanogram quantities of the active agent are also released in a controlled or sustained manner. The nanogram quantities of the active agent and/or the controlled or sustained release can contribute to reduced toxicity of the compositions and methods of the present invention as compared to other delivery system, which uses high dose of active agent and has suboptimal release kinetics. In various embodiments, the amount of active agent present in a scaffold may vary according to the size of the scaffold. For example, the growth factor may be present at about 0.03 ng/mm³ (the ratio of the amount of active agent in weight to the volume of the scaffold) to about 350 ng/mm³, such as between about 0.1 ng/mm³ and about 300 ng/mm³ , between about 0.5 ng/mm³ and about 250 ng/mm³, between about 1 ng/mm³ and about 200 ng/mm³, between about 2 ng/mm³ and about 150 ng/mm³, between about 3 ng/mm³ and about 100 ng/mm³, between about 4 ng/mm³ and about 50 ng/mm³, between about 5 ng/mm³ and 25 ng/mm³, between about 6 ng/mm³ and about 10 ng/mm³, or between about 6.5 ng/mm³ and about 7.0 ng/mm³. In some embodiments, the amount of active agent may be present at between about 300 ng/mm³ and about 350 µg/mm³, such as between about 400 ng/mm³ and between about 300 µg/mm³, between about 500 ng/mm³ and about 200 µg/mm³, between about 1 µg/mm³ and about 100 µg/mm³, between about 5 µg/mm³ and about 50 µg/mm³, between about 10 µg/mm³ and about 25 µg/mm³. In some embodiments of the above aspects or any other aspect of the invention delineated herein, the active agent is covalently or non-covalently linked or attached to the scaffold composition. In some embodiments, one or more active agents disclosed herein is incorporated on, into, or present within the structure or pores of, the scaffold composition. In some embodiments, the active agent is covalently linked to the scaffold. In one embodiment, the active agent is covalently linked to the scaffold utilizing click chemistry. In another embodiment, the active agent is covalently linked to the scaffold utilizing N- hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry, NHS and dicyclohexylcarbodiimide (DCC) chemistry, avidin-biotin reaction, azide and dibenzocycloocytne chemistry, tetrazine and transcyclooctene chemistry, tetrazine and norbornene chemistry, or di-sulfide chemistry. GROWTH FACTORS The compositions of the present invention can comprise a growth factor. However, in certain embodiments, the composition of the present invention does not comprise a growth factor. The term “growth factor,” as used herein, refers to an agent that is capable of stimulating cellular growth, proliferation, healing, and/or cellular differentiation. In certain embodiments, growth factors are polypeptides. Growth factor polypeptides typically act as signaling molecules. In certain embodiments, the growth factor polypeptides are cytokines. In certain embodiments, the growth factor can recruit a cell to the scaffold following the administration of the composition to a subject. The recruited cell may be autologous. For example, the recruited cell may be a stromal cell from the subject. In certain embodiments, the autologous cell may be a stem cell (e.g., umbilical cord stem cells) of the subject. The recruited cell may also be syngeneic, allogeneic or xenogeneic. As used herein, the term “syngeneic” refers to genetically identical, or sufficiently identical and immunologically compatible as to allow for transplantation. For example, syngeneic cells may include transplanted cells obtained from an identical twin. As used herein, the term “allogeneic” refers to cells that are genetically dissimilar, although from individuals of the same species. As used herein, the term “xenogeneic” refers to cells derived from a different species and therefore genetically different. For example, the recruited cell may be a donor cell in a transplantation. In certain embodiments, the transplantation is a hematopoietic stem cell transplantation (HSCT). As used herein, HSCT refers to the transplantation of multipotent hematopoietic stem cells or hematopoietic progenitor cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. HSCT may be autologous (the patient's own stem cells or progenitor cells are used), allogeneic (the stem cells or progenitor cells come from a donor), syngeneic (from an identical twin) or xenogenic (from different species). The growth factors of the present invention may induce the formation of a tissue or organ within or around the administered composition. In certain embodiments, the tissue or organ is a bony tissue or hematopoietic tissue. The tissue formation may be restricted to the scaffold of the composition. Methods of incorporating polypeptides (e.g., growth factor polypeptides) are known in the art. See, US Patent Nos.: 8,728,456; 8,067,237; and 10,045,947; US Patent Publication No.: US20140079752; International Patent Publication No.: WO2017/136837; incorporated herein by reference in their entirety. The release of the growth factor polypeptides may be controlled. The methods of controlled release of polypeptides (e.g., growth factor polypeptides) are known in the art. See, US Patent Nos.: 8,728,456; 8,067,237; 10,045,946, incorporated by reference in their entirety. In certain embodiments, the growth factors (e.g., BMP-2) may be released over an extended period of time, such as 7-30 days or longer. The controlled release of the growth factors may affect the timing of the formation of the tissue or organ within the scaffold. In certain examples, the release of the growth factors is controlled with the goal of creating a functional, active bone nodule or tissue within one to two weeks after subcutaneous injection of the compositions of the present invention. In certain embodiments, the growth factors retain their bioactivity over an extended period of time. The term “bioactivity,” as used herein, refers to the beneficial or adverse effects of an agent, such as a growth factor. The bioactivity of the growth factor may be measured by any appropriate means. For example, the bioactivity of BMP-2 may be measured by its capacity to induce the formation of bone nodule or tissue and/or recruit cells into the scaffold. In certain example, the growth factors retain their bioactivity for at least 10 days, 12 days, 14 days, 20 days, or 30 days after the incorporation of the growth factors into the scaffold. Exemplary growth factors include, but are not limited to, bone morphogenetic proteins (BMP), epidermal growth factor (EGF), transforming growth factor beta (TGF-β), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), neurotrophins, Platelet-derived growth factor (PDGF), erythropoietin (EPO), thrombopoietin (TPO), myostatin (GDF-8), growth differentiation factor-9 (GDF9), acidic fibroblast growth factor (aFGF or FGF-1), basic fibroblast growth factor (bFGF or FGF-2), epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), and interleukins. In some embodiments, the growth factor comprises a protein belonging to the transforming growth factor beta (TGF-β) superfamily. As used herein, TGF-β superfamily is a large group of structurally related cell regulatory proteins. TGF-β superfamily includes four major subfamilies: the TGF-β subfamily, the bone morphogenetic proteins and the growth differentiation factors, the activing and inhibin subfamilies, and a group encompassing various divergent members. Proteins from the TGF-β superfamily are active as homo- or heterodimer, the two chains being linked by a single disulfide bond. TGF-β superfamily proteins interact with a conserved family of cell surface serine/threonine-specific protein kinase receptors, and generate intracellular signals using a conserved family of proteins called SMADs. TGF-β superfamily proteins play important roles in the regulation of basic biological processes such as growth, development, tissue homeostasis and regulation of the immune system. Exemplary TGF-β superfamily proteins include, but are not limited to, AMH, ARTN, BMP10, BMP15, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, GDF1, GDF10, GDF11, GDF15, GDF2, GDF3, GDF3A, GDF5, GDF6, GDF7, GDF8, GDF9, GDNF, INHA, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, MSTN, NODAL, NRTN, PSPN, TGF-β1, TGF-β2, TGF-β3, and TGF-β4. In a particular embodiment, the growth factor is BMP2. In certain embodiments, the growth factor comprises a bone morphogenetic protein (BMP). As used herein, a BMP is a protein belonging to a group of growth factors also known as cytokines and as metabologens. BMPs can induce the formation of bone and cartilage and constitute a group of important morphogenetic signals, orchestrating tissue architecture throughout the body. Absence or deficiency of BMP signaling may be an important factor in diseases or disorders. In certain embodiments, the BMP is selected from a group consisting of a BMP-2, a BMP-4, a BMP-6, a BMP-7, a BMP-12, a BMP-14, and any combination thereof. In certain embodiments, the BMP is BMP-2. BMP-2 plays an important role in the development of bone and cartilage. BMP-2 can potently induce osteoblast differentiation in a variety of cell types. In certain embodiments, the growth factor comprises a TGF-β subfamily protein. As used herein, TGF-β subfamily protein or TGF-β is a multifunctional cytokine that includes four different isoforms (TGF-β1, TGF-β2, TGF-β3, and TGF-β4). Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors, which is composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. In certain embodiments, the growth factor comprises a TGF-β1. TGF-β1 plays a role in the induction from CD4+ T cells of both induced Tregs (iTregs), which have a regulatory function, and Th17 cells, which secrete pro-inflammatory cytokines. TGF-β1 alone precipitates the expression of Foxp3 and Treg differentiation from activated T helper cells. The growth factors, (e.g., BMP-2 or TGF-β1), may be isolated from endogenous sources or synthesized in vivo or in vitro. Endogenous growth factor polypeptides may be isolated from healthy human tissue. Synthetic growth factor polypeptides are synthesized in vivo following transfection or transformation of template DNA into a host organism or cell, e.g., a mammalian or human cell line. Alternatively, synthetic growth factor polypeptides are synthesized in vitro by cell free translation or other art-recognized methods Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, NY, Vol.1, 2, 3 (1989), herein incorporated by reference. In certain embodiments, growth factor (e.g., BMP-2 or TGF-β1) polypeptides may be recombinant. In some embodiments, growth factor polypeptides are humanized derivatives of mammalian growth factor polypeptides. Exemplary mammalian species from which growth factor polypeptides are derived include, but are not limited to, mouse, rat, hamster, guinea pig, ferret, cat, dog, monkey, or primate. In some embodiments, the growth factor is a recombinant human protein . In some embodiments, the growth factor is a recombinant murine (mouse) protein. In some embodiments, the growth factor is a humanized derivative of a recombinant mouse protein. In certain embodiments, the growth factor polypeptides may be modified to increase protein stability in vivo. In certain embodiments, the growth factor polypeptides may be engineered to be more or less immunogenic. The terms “immunogenic” and “immunogenicity” refer to the ability of a particular substance, such as a protein, an antigen, or an epitope, to provoke an immune response in the body of a human and other animal. In certain embodiments, the growth factors may be present at between about 0.001 nmol and about 1000 nmol per scaffold, or about 0.001 and about 100 nmol per scaffold, or about 0.001 nmol and about 1 nmol per scaffold. In some embodiments, the growth factors may be present at between about 1 ng to 1000 micrograms per scaffold. For example, the growth factors may be present at an amount between about 1 µg and about 1000 µg, between about 1 µg and 500 µg, between about 1 µg and about 200 µg, between about 1 µg and about 100 µg, between about 1 µg and about 50 µg, or between about 1 µg and 10 µg. In certain embodiments, the composition of the present invention comprises nanogram quantities of growth factors (e.g., about 1 ng to about 1000 ng of BMP-2). For example, the growth factors may be present at an amount between about 5 ng and about 500 ng, between about 5 ng and about 250 ng, between about 5 ng and about 200 ng, between about 10 ng and about 200 ng, between about 25 ng and about 200 ng, between about 50 ng and 200 ng, between about 100 ng and 200 ng, and about 200 ng. Nanogram quantities of the growth factor are also released in a controlled manner. The nanogram quantities of the growth factors and/or the controlled release can contribute to reduced toxicity of the compositions and methods of the present invention as compared to other delivery system, which uses high dose of growth factors and has suboptimal release kinetics. In various embodiments, the amount of growth factors present in a scaffold may vary according to the size of the scaffold. For example, the growth factor may be present at about 0.03 ng/mm³ (the ratio of the amount of growth factors in weight to the volume of the scaffold) to about 350 ng/mm³, such as between about 0.1 ng/mm³ and about 300 ng/mm³ , between about 0.5 ng/mm³ and about 250 ng/mm³, between about 1 ng/mm³ and about 200 ng/mm³, between about 2 ng/mm³ and about 150 ng/mm³, between about 3 ng/mm³ and about 100 ng/mm³, between about 4 ng/mm³ and about 50 ng/mm³, between about 5 ng/mm³ and 25 ng/mm³, between about 6 ng/mm³ and about 10 ng/mm³, or between about 6.5 ng/mm³ and about 7.0 ng/mm³. In some embodiments, the amount of growth factors may be present at between about 300 ng/mm³ and about 350 µg/mm³, such as between about 400 ng/mm³ and between about 300 µg/mm³, between about 500 ng/mm³ and about 200 µg/mm³, between about 1 µg/mm³ and about 100 µg/mm³, between about 5 µg/mm³ and about 50 µg/mm³, between about 10 µg/mm³ and about 25 µg/mm³. DIFFERENTIATION FACTORS The composition of the present invention can comprise a differentiation factor. However, in certain embodiments, the composition of the present invention does not comprise a differentiation factor, for example, that induces the differentiation of a hematopoietic stem cell into a T cell progenitor cell. As used herein, a differentiation factor is an agent that can induce the differentiation of a cell, for example, a recruited cell. In certain embodiments, the differentiation factor is a polypeptide. As used herein, “differentiation,” “cell differentiation,” “cellular differentiation,” or other similar terms refer to the process where a cell changes from one cell type to another. In certain embodiments, the cell changes to a more specialized type, e.g., from a stem cell or a progenitor cell to a T cell progenitor cell. Differentiation occurs numerous times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Differentiation may change a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes may be due to highly controlled modifications in gene expression. Among dividing cells, there are multiple levels of cell potency, the cell's ability to differentiate into other cell types. A greater potency indicates a larger number of cell types that can be derived. A cell that can differentiate into all cell types, including the placental tissue, is known as totipotent. A cell that can differentiate into all cell types of the adult organism is known as pluripotent. In mammals, e.g., human being, a pluripotent cell may include embryonic stem cells and adult pluripotent cells. Induced pluripotent stem (iPS) cells may be created from fibroblasts by induced expression of certain transcription factors, e.g., Oct4, Sox2, c-Myc, and KIF4. A multipotent cell is one that can differentiate into multiple different, but closely related cell types. Oligopotent cells are more restricted than multipotent, but can still differentiate into a few closely related cell types. Finally, unipotent cells can differentiate into only one cell type, but are capable of self-renewal. In certain embodiments, the differentiation factors of the present invention induce the differentiation of stem cells or progenitor cells into T-cell progenitor cells. As used herein, the term “T cell progenitor cell” refers to a progenitor cell that ultimately can differentiate to a T lymphocyte (T cell). The term “lymphocyte,” as used herein, refers to one of the subtypes of white blood cell in a vertebrate’s (e.g., human being) immune system. Lymphocytes include natural killer cells, T cells, and B cells. Lymphocytes originate from a common lymphoid progenitor during hematopoiesis, a process during which stem cells differentiate into several kinds of blood cells within the bone marrow, before differentiating into their distinct lymphocyte types. In some embodiments, the T cell progenitor cell comprises a common lymphoid progenitor cell. The term “common lymphoid progenitor cell,” as used herein, refers to the earliest lymphoid progenitor cells, which give rise to lymphocytes including T-lineage cells, B-lineage cells, and natural killer (NK) cells. In various embodiment, the T cell progenitor cell comprises a T cell competent common lymphoid progenitor cell. The term “T cell competent common lymphoid progenitor cell,” as used herein, refers to a common lymphoid progenitor cell that differentiates into T-lineage progenitor cell. A T cell competent common lymphoid progenitor is usually characterized by lacking of biomarker Ly6D. The composition of the present invention can create an ectopic niche that mimics important features of bone marrow and induces the differentiation of stem cells or progenitor cells into T cell progenitor cells. In certain embodiments, the lymphocytes comprise T cells. In some embodiments, the T cells are naïve T cells. As used herein, a naïve T cell is a T cell that has differentiated in bone marrow. Naïve T cells may include CD4⁺ T cells, CD8⁺ T cells, and regulatory T cells (T_reg). In certain embodiments, the differentiation factors induce the differentiation of the recruited cells into T cell progenitor cells. In certain embodiments, the differentiation factors induce the differentiation of the recruited cells into T cell progenitor cells through the Notch signaling pathway. The Notch signaling pathway is a highly conserved cell signaling system present in many multicellular organisms. Mammals possess four different Notch receptors, referred to as Notch1, Notch2, Notch3, and Notch4. Notch signaling plays an important role in T cell lineage differentiation from common lymphoid progenitor cells. In certain embodiments, the differentiation factors bind to one or more Notch receptors and activates the Notch signaling pathway. In certain embodiments, the differentiation factor is selected from a group consisting of a Delta-like 1 (DLL-1), a Delta-like 2 (DLL-2), a Delta-like 3 (DLL-3), a Delta-like 3 (DLL-3), a Delta-like 4 (DLL-4), a Jagged 1, a Jagged 2, and any combination thereof. In certain embodiments, the binding of the differentiation factor to one or more Notch receptors activates the Notch signaling pathway and induces T cell lineage differentiation. In certain embodiments, the differentiation factor is a Delta-like 4 (DLL-4). DLL-4 is a protein that is a homolog of the Drosophila Delta protein. The Delta protein family includes Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. In certain embodiments, the differentiation factor polypeptides are isolated from endogenous sources or synthesized in vivo or in vitro. Endogenous differentiation factor polypeptides may be isolated from healthy human tissue. Synthetic differentiation factor polypeptides are synthesized in vivo following transfection or transformation of template DNA into a host organism or cell, e.g., a mammal or cultured human cell line. Alternatively, synthetic differentiation factor polypeptides are synthesized in vitro by cell free translation or other art-recognized methods Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, NY, Vol.1, 2, 3 (1989), herein incorporated by reference). In certain embodiments, differentiation factor polypeptides may be recombinant. In some embodiments, the differentiation factor polypeptides are humanized derivatives of mammalian differentiation factor polypeptides. Exemplary mammalian species from which the differentiation factor polypeptides are derived include, but are not limited to, mouse, rat, hamster, guinea pig, ferret, cat, dog, monkey, or primate. In some embodiments, the differentiation factor is a recombinant human protein . In some embodiments, the differentiation factor is a recombinant murine (mouse) protein . In some embodiments, the differentiation factor is a humanized derivative of a recombinant mouse protein. In certain embodiments, the differentiation factor polypeptides may be modified to achieve a desired activity, for example, to increase protein stability in vivo. In certain embodiments, the differentiation factor polypeptides may be engineered to be more or less immunogenic. In certain embodiments, the differentiation factor (e.g., DLL-4) may be covalently linked to the scaffold of the present invention. For example, rather than being released from a scaffold material, a differentiation factor may be covalently bound to polymer backbone and retained within the composition that forms following implantation of the composition in the subject. By covalently binding or coupling a differentiation factor to the scaffold material, such differentiation factor will be retained within the scaffold that forms following administration of the composition to a subject, and thus will be available to promote the differentiation of stem cells or progenitor cells, as contemplated herein. In certain embodiments, the differentiation factors are conjugated to the scaffold material utilizing N- hydroxysuccinimide (NHS) and l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. Any methods of covalently binding or coupling differentiation factors known in the art may be used and are not limited. See "Bioconjugate Techniques Bioconjugate Techniques (Third Addition)", Greg T. Hermanson, Academic , Greg T. Hermanson, Academic Press, 2013 Press, 2013. In some embodiments, the differentiation factor may be covalently linked to the scaffold utilizing click chemistry. The methods of covalently binding or coupling differentiation factors include, but are not limited to, avidin-biotin reaction, azide and dibenzocycloocytne chemistry, tetrazine and transcyclooctene chemistry, tetrazine and norbornene chemistry, or di-sulfide bond. In certain embodiments, the differentiation factors (e.g., DLL-4) of the present invention further comprise a tether (e.g., PEG, PEG_2k) and a methacrylate group (MA). In certain embodiments, the differentiation factor is methacrylated DLL-4-PEG2k. In certain embodiments, the covalent linking retains the differentiation factors within the scaffold to provide the differentiation signal to the recruited cells in the scaffold. For example, less than 1 % of the total differentiation factor is detected outside of the scaffold. The bioactivity of the differentiation factor may be retained for an extended period of time, such as at least three months after incorporation to the scaffold. The bioactivity of the differentiation factors may be measured by any appropriate methods, such as a colorimetric assay for DLL-4. In certain embodiments, the differentiation factors may be present at between about 0.01 nmol and 1000 nmol, about 0.1 nmol and 100 nmol, or about 1 nmol and 10 nmol per scaffold. In some embodiments, the differentiation factors may be present at between about 1 ng and 1000 micrograms per scaffold. For example, the differentiation factor may be present at between about 10 ng and about 500 µg, between about 50 ng and about 250 µg, between about 100 ng and about 200 µg, between about 1 µg and about 100 µg, between about 1 µg and about 50 µg, between about 1 µg and about 25 µg, between about 1 µg and about 10 µg, between about 2 µg and about 10 µg, or about 6 µg. In various embodiments, the amount of differentiation factor present in a scaffold may vary according to the size of the scaffold. For example, the differentiation factor may be present at about 0.03 ng/mm³ (the ratio of the amount of differentiation factor in weight to the volume of the scaffold) to about 350 µg/mm³, such as between about 0.1 ng/mm³ and about 300 µg/mm³, between about 1 ng/mm³ and about 250 µg/mm³, between about 10 ng/mm³ and about 200 µg/mm³, between about 0.1 µg/mm³ and about 100 µg/mm³, between about 0.1 µg/mm³ and 50 about µg/mm³, or between about 0.1 µg/mm³ and about 20 µg/mm³, between about 0.1 µg/mm³ and about 10 µg/mm³, between about 0.1 µg/mm³ and about 5 µg/mm³, between about 0.1 µg/mm³ and about 1 µg/mm³, between about 0.1 µg/mm³ and 0.5 µg/mm³, or about 0.2 µg/mm³. In certain embodiments, the DLL-4 may be present at about 6 µg per scaffold. HOMING FACTORS In certain embodiments, the composition of the present invention may further comprise a homing factor. However, in certain embodiments, the composition of the present invention does not comprise a homing factor. As used herein, the term “homing factor” refers to an agent that is capable of inducing directed movement of a cell, e.g., a stem cell or a progenitor cell. In certain embodiments, the homing factors of the present invention are signaling proteins that can induce directed chemotaxis in nearby responsive cells. In various embodiments, the homing factors are cytokines and/or chemokines. In certain embodiments, the inclusion of such homing factors in the compositions of the present invention promotes the homing of cells (e.g., transplanted stem cells and/or progenitor cells) to the scaffold composition administered to a subject. In certain aspects, such homing factors promote the infiltration of the cells (e.g., transplanted stem cells or progenitor cells) to the scaffold composition administered to the subject. In some embodiments, the homing factors comprise stromal cell derived factor (SDF-1). In certain embodiments, the homing factors are encapsulated in the material. In certain embodiments, the homing factors are released from the material over an extended period of time (e.g., about 7-30 days or longer, about 17-18 days). In certain embodiments, the homing factors retain their bioactivity over an extended period of time. The bioactivity of the growth factor may be measured by any appropriate means. In certain example, the homing factors retain their bioactivity for at least 10 days, 12 days, 14 days, 20 days, or 30 days after the incorporation of the homing factors into the scaffold. In some embodiments, the homing factors may be present at between about 0.01 nmol and 1000 nmol, about 0.1 nmol and 100 nmol, or about 1 nmol and 10 nmol per scaffold. In some embodiments, the homing factors may be present at between about 1 ng and 1000 micrograms per scaffold. For example, the homing factor may be present at between about 10 ng and about 500 µg, between about 50 ng and about 250 µg, between about 100 ng and about 200 µg, between about 1 µg and about 100 µg, between about 1 µg and about 50 µg, between about 1 µg and about 25 µg, between about 1 µg and about 10 µg, between about 2 µg and about 10 µg, or about 6 µg. In various embodiments, the amount of differentiation factor present in a scaffold may vary according to the size of the scaffold. For example, the differentiation factor may be present at about 0.03 ng/mm³ (the ratio of the amount of differentiation factor in weight to the volume of the scaffold) to about 350 µg/mm³, such as between about 0.1 ng/mm³ and about 300 µg/mm³, between about 1 ng/mm³ and about 250 µg/mm³, between about 10 ng/mm³ and about 200 µg/mm³, between about 0.1 µg/mm³ and about 100 µg/mm³, between about 0.1 µg/mm³ and 50 about µg/mm³, or between about 0.1 µg/mm³ and about 20 µg/mm³, between about 0.1 µg/mm³ and about 10 µg/mm³, between about 0.1 µg/mm³ and about 5 µg/mm³, between about 0.1 µg/mm³ and about 1 µg/mm³, between about 0.1 µg/mm³ and 0.5 µg/mm³, or about 0.2 µg/mm³. DETECTABLE AGENT In certain embodiments, the composition of the present invention may further comprise a a detectable agent. Incorporation of a detectable agent into a composition of the present invention can allow for the tracking, labeling, and/or visualization of the composition and its degradation after being administered to a subject. Further, active agents can also be labeled with a detectable agent, prior to being incorporated into a composition of the invention, which allows for the tracking, labeling and/or visualization of the active agent in the subject. Such detectable agents may include, but are not limited to a dye, a fluorophore, a fluorescent compound, a luminescent compound, a chemiluminescent compound, a radioisotope, a paramagnetic metal ion, a nanoparticle, and a quantum dot, or a combination thereof. Exemplary fluorescent detectable agents include fluorescein, fluorescein isothiocyanate, rhodamine, 5-dimethylamine-1-napthalenesulfonyl chloride, phycoerythrin and the like. Thus, in one embodiment of the present invention the compositions described herein, comprising a detectable agent can be administered to a subject and be used for a variety of diagnostic and/or therapeutic methods. In certain embodiments, the detectable agent is for detecting the scaffold and/or active agent in vivo. In certain embodiments, the detectable agent is for assessing the level of degradation of the scaffold composition. In certain embodiments, the detectable agent is for assessing levels of functional innate leukocytes. In certain embodiments, the detectable agent can be used for assessing the level of degradation of the scaffold by detecting the level of the detectable agent and comparing to a detectable agent reference level, optionally, wherein the detectable agent reference level is the level of the detectable agent upon administration of the scaffold composition or at an earlier time point after administration of the scaffold composition to the subject. In certain embodiments, the detectable agent is detectable by eye, fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), multi-mode imaging, ultrasound imaging (USI), photoacoustic imaging (PAI), and/or optical coherence tomography (OCT). In some embodiments of the above aspects or any other aspect of the invention delineated herein, the detectable agent is covalently or non-covalently linked or attached to the scaffold composition. In some embodiments, one or more detectable agent disclosed herein is incorporated on, into, or present within the structure or pores of, the scaffold composition. In some embodiments, the detectable agent is covalently linked to the scaffold. In one embodiment, the detectable agent is covalently linked to the scaffold utilizing click chemistry. In another embodiment, the detectable agent is covalently linked to the scaffold utilizing N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry, NHS and dicyclohexylcarbodiimide (DCC) chemistry, avidin-biotin reaction, azide and dibenzocycloocytne chemistry, tetrazine and transcyclooctene chemistry, tetrazine and norbornene chemistry, or di-sulfide chemistry. COMBINATION THERAPY In various embodiments, the compositions of the present invention may be used in combination with an additional active agent or therapy, such as one or more cancer therapies. The cancer therapies can include, but are not limited to, surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, hormone therapy, or stem cell transplant. These therapies are well known in the art. See, e.g., https://www.cancer.gov/about- cancer/treatment/types. In some embodiments, the compositions of the present invention may be used in combination with a PD-1 inhibitor (e.g., an anti-PD-1 antibody such as nivolumab, pembrolizumab, pidilizumab, or BGB-A317), a PD-L1 inhibitor (e.g., an anti-PD-L1 antibody such as avelumab, atezolizumab, durvalumab, or MDX-1105), a CTLA-4 inhibitor (e.g., ipilimumab), a TIM3 inhibitor, a BTLA inhibitor, a TIGIT inhibitor, a CD47 inhibitor, a GITR inhibitor, an antagonist of another T cell co-inhibitor or ligand (e.g., an antibody to CD-28, 2B4, LY108, LAIR1, ICOS, CD160 or VISTA), an indoleamine-2,3-dioxygenase (IDO) inhibitor, a vascular endothelial growth factor (VEGF) antagonist [e.g., a “VEGF- Trap” such as aflibercept or other VEGF-inhibiting fusion protein as set forth in US 7,087,411, or an anti-VEGF antibody or antigen-binding fragment thereof (e.g., bevacizumab, or ranibizumab) or a small molecule kinase inhibitor of VEGF receptor (e.g., sunitinib, sorafenib, or pazopanib)], an Ang2 inhibitor (e.g., nesvacumab), a transforming growth factor beta (TGFβ) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor (e.g., erlotinib, cetuximab), a CD20 inhibitor (e.g., an anti-CD20 antibody such as rituximab), a human epidermal growth factor receptor 2 (HER2) inhibitor (e.g., trastuzumab), an anaplastic lymphoma kinase (ALK) inhibitor (e.g., crizotinib, ceritinib, alectinib, brigatinib, lorlatinib), an antibody to a tumor-specific antigen [e.g., CA9, CA125, melanoma-associated antigen 3 (MAGE3), carcinoembryonic antigen (CEA), vimentin, tumor-M2-PK, prostate-specific antigen (PSA), mucin-1, MART-1, and CA19-9], a vaccine (e.g., Bacillus Calmette-Guerin, a cancer vaccine), an adjuvant to increase antigen presentation (e.g., granulocyte-macrophage colony-stimulating factor), a bispecific antibody (e.g., CD3xCD20 bispecific antibody, or PSMAxCD3 bispecific antibody), a cytotoxin, a chemotherapeutic agent (e.g., dacarbazine, temozolomide, cyclophosphamide, docetaxel, doxorubicin, daunorubicin, cisplatin, carboplatin, gemcitabine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, and vincristine), cyclophosphamide, radiotherapy, surgery, an IL-6R inhibitor (e.g., sarilumab), an IL-4R inhibitor (e.g., dupilumab), an IL-10 inhibitor, a cytokine such as IL-2, IL-7, IL-21, and IL-15, an antibody-drug conjugate (ADC) (e.g., anti-CD19-DM4 ADC, and anti-DS6-DM4 ADC), an anti-inflammatory drug (e.g., corticosteroids, and non-steroidal anti-inflammatory drugs), a dietary supplement such as anti-oxidants or any other therapy care to treat cancer. In certain embodiments, the compositions of the present invention may be used in combination with cancer vaccines including dendritic cell vaccines, oncolytic viruses, tumor cell vaccines, etc. When the composition is used in combination with one or more other active agents or therapies, such as a chemotherapeutic agent, the one or more other active agents or therapies may be administered prior to, concurrently with, or after the administration of the composition. In some particular embodiments, the one or more other active agents or therapies may be administered prior to the administration of the composition. The one or more other active agents or therapies may be administered between 1 day and 2 years prior to the administration of the vaccine composition, for example, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months, 18 months, or two years prior to the administration of the vaccine composition. In still some particular embodiments, the one or more other active agents or therapies may be administered after the administration of the vaccine composition. The one or more other active agents or therapies may be administered between 1 day and 2 years after the administration of the vaccine composition, for example, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months, 18 months, or two years prior to the administration of the vaccine composition. It is intended that values and ranges intermediate to the recited values are part of this invention. EXEMPLARY SCAFFOLD COMPOSITIONS The present invention provides scaffold compositions for delivering an active agent to a subject. The composition and methods disclosed herein provide a means to treat and/or prevent diseases associated with a deficiency in levels of functional innate leukocytes, e.g., neutrophils. The compositions of the present invention include a scaffold composition, for example, a hydrogel or a cryogel, comprising a hyaluronic acid and, optionally, an active agent In one aspect, the present invention provides an injectable composition, comprising a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof, and an active agent that increases the number of and/or modulates the activity of an innate leukocyte; and/or a detectable agent that allows for assessment of degradation of the scaffold composition and/or assessment of the levels of functional innate leukocytes, e.g., neutrophils, in vivo. In some embodiments, the injectable composition comprises both the active agent and the detectable agent. In some embodiments, the innate leukocytes are neutrophils. In some embodiments, the active agent is G-CSF. In another aspect, the present invention provides an injectable composition, comprising a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof, and at least one of (i) an active agent that increases the number of and/or modulates the activity of an innate leukocyte; and/or (ii) a detectable agent that allows for assessment of degradation of the scaffold composition and/or assessment of the levels of functional innate leukocytes, e.g., neutrophils, in vivo. In some embodiments, the injectable composition comprises both the active agent and the detectable agent. In some embodiments, the innate leukocytes are neutrophils. In some embodiments, the active agent is G-CSF. In one aspect, the present invention provides an injectable composition, comprising a scaffold encapsulating an effective amount of an active agent that modulates the number and/or function of an innate leukocyte, wherein the scaffold is formulated to degrade in vivo by immune-responsive degradation to sustain the release of the active agent over a period of time sufficient to modulate the number and/or function of the innate leukocyte. In some embodiments, the immune-responsive degradation comprises neutrophil- responsive degradation. In some embodiments, the injectable composition further comprises a detectable agent for monitoring the immune-responsive degradation of the scaffold and/or assessing neutrophil functionality in vivo. In some embodiments, the detectable agent is selected from the group consisting of a dye, a fluorophore, a fluorescent compound, a luminescent compound, a chemiluminescent compound, a radioisotope, a paramagnetic metal ion, a nanoparticle, and a quantum dot, or a combination thereof. In some embodiments, the detectable agent comprises a dye. In some embodiments, the detectable agent is detectable by eye. In some embodiments, the detectable agent is detectable by fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), multi-mode imaging, ultrasound imaging (USI), photoacoustic imaging (PAI), and/or optical coherence tomography (OCT). In some embodiments, the active agent comprises an amino acid, a nucleic acid, a small molecule, or a combination thereof. In some embodiments, the active agent comprises a protein, optionally, wherein the protein is an isolated protein and/or a recombinant protein. In some embodiments, the active agent comprises a cytokine, a chemokine, and/or a growth factor. In some embodiments, the active agent comprises a cytokine. In some embodiments, the cytokine comprises a pro-inflammatory cytokine and/or an anti-inflammatory cytokine. In some embodiments, the active agent is selected from the group consisting of a granulocyte colony stimulating factor (G-CSF), a granulocyte-macrophage colony-stimulating factor (GM-CSF), a bone morphogenetic protein 2 (BMP2), a stromal cell-derived factor (SDF), a platelet activating factor (PAF), a tumor necrosis factor α (TNFα), an interleukin-1 (IL-1), an interleukin-1α (IL-1α), an interleukin-1β (IL-1β), an interleukin-2 (IL-2), an interleukin-3 (IL-3), an interleukin-4 (IL-4), an interleukin-5 (IL-5), an interleukin-6 (IL-6), an interleukin- 7 (IL-7), an interleukin-8 (IL-8), an interleukin-9 (IL-9), an interleukin-10 (IL-10), an interleukin-11 (IL-11), an interleukin-12 (IL-12), an interleukin-13 (IL-13), an interleukin-14 (IL-14), an interleukin-15 (IL-15), an interleukin-16 (IL-16), an interleukin-17 (IL-17), an interleukin-18 (IL-18), an interleukin-19 (IL-19), an interleukin-20 (IL-20), an interleukin-21 (IL-21), an interleukin-22 (IL-22), an interleukin-23 (IL-23), an interleukin-24 (IL-24), an interleukin-25 (IL-25), an interleukin-26 (IL-26), an interleukin-27 (IL-27), an interleukin-28 (IL-28), an interleukin-29 (IL-29), an interleukin-30 (IL-30), an interleukin-31 (IL-31), an interleukin-32 (IL-32), an interleukin-33 (IL-33), an interleukin-34 (IL-34), an interleukin-35 (IL-35), an interleukin-36 (IL-36), an interleukin-1 receptor antagonist (IL-1Ra), a growth- related gene product-α (GRO-α), a growth-related gene product-β (GRO-β), a macrophage infiltrating protein-1α (MCP-1α), a macrophage infiltrating protein-1β (MCP-1β), a cytokine- induced chemoattractant (CINC), an interferon-α (IFN-α), an interferon-β (IFN-β), an interferon-γ (IFN-γ), a Fas ligand (FasL), a CD30 ligand (CD30L), a vascular endothelial growth factor (VEGF), a hepatocyte frowth factor (HGF), a transforming growth factor alpha (TGF-α), an oncostain (OSM), a neurotrophin, a monocyte chemoattractant protein-1 (MCP- 1), a stem cell factor (SCF), a complement 5a (C5a), and an erythropoietin (EPO). In some embodiments, the active agent comprises a G-CSF. In some embodiments, the active agent comprises a polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G- CSF). In some embodiments, the injectable composition further comprises an additional active agent. In some embodiments, the injectable composition enhances the number and/or function of the innate leukocyte. In some embodiments, the injectable composition not comprise a differentiation factor that induces the differentiation of a hematopoietic stem cell into a T cell progenitor cell. In some embodiments, the innate leukocyte is selected from the group consisting of a natural killer cell, a mast cell, an eosinophil, a basophil, a macrophage, a dendritic cell, a gamma-delta (γδ) T cell, and a neutrophil, or a combination thereof. In some embodiments, the innate leukocyte is not a dendritic cell. In some embodiments, the innate leukocyte comprises a neutrophil. In some embodiments, the scaffold comprises a hydrogel, optionally, wherein the hydrogel gel comprises a cryogel. In some embodiments, the hydrogel or cryogel is biodegradable. In some embodiments, the immune-responsive degradation of the hydrogel or cryogel is facilitated by an enzyme produced by the innate leukocyte and/or by innate leukocyte-mediated oxidation. In some embodiments, the hydrogel or cryogel comprises a polymer, and wherein the polymer is modified to be attached to a moiety that is a substrate of the enzyme. In some embodiments, the enzyme comprises a hyaluronidase. In some embodiments, the immune-responsive degradation of the hydrogel or cryogel results in the release of the active agent, the detectable agent, and/or the additional active agent from the scaffold. In some embodiments, the enzyme increases the degradation of the hydrogel or cryogel in vivo by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99% or more compared to a reference level; and/or the enzyme increases the degradation of the hydrogel or cryogel in vivo by about 1-fold, about 2-fold, about 3-fold, or more compared to a reference level. In some embodiments, at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99% or more of the hydrogel or cryogel degrades in vivo over a time period of about 1 day to about 60 days. In some embodiments, the hydrogel or cryogel comprises a crosslinked polymer, and wherein the polymer comprises a polymer selected from the group consisting of an alginate, a collagen, a gelatin, a hyaluronic acid, and a laminin, or a combination thereof. In some embodiments, the polymer comprises a hyaluronic acid. In some embodiments, the hydrogel or cryogel comprises a covalently crosslinked polymer. In some embodiments, the polymer is covalently crosslinked via click chemistry. In one aspect, the present invention provides a scaffold composition comprising a click-functionalized hyaluronic acid and an active agent. In one aspect, the present invention provides a scaffold composition comprising a click-functionalized HA cryogels. In some embodiments, the scaffold composition comprises a lyophilized HA cryogels. In some embodiments, the scaffold compositions is made from a polymer solution comprising about 0.1 wt% to about 10 wt% polymer. In some embodiments, the scaffold compositions is made from a polymer solution, such as an HA solution, comprising about about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 5.5 wt%, about 6 wt%, about 6.5 wt%, about 7 wt%, about 7.5 wt%, about 8 wt%, about 8.5 wt%, about 9 wt%, about 9.5 wt%, or about 10 wt% polymer. In some embodiments, the scaffold composition comprises a high molecular weight HA (e.g., about 1.8 MDa). In certain embodiments, the click-functionalized hyaluronic acid may comprise tetrazine functionalized HA (HA-Tz) and/or norbornene functionalized HA (HA-Nb), for example, prepared by reacting tetrazine amine or norbornene amine to HA using EDC/NHS carbodiimide chemistry. In some embodiments, the polymer comprises a first polymer and a second polymer; the first polymer is functionalized with a first bioorthogonal functional group; the second polymer is functionalized with a second bioorthogonal functional group; and the first and the second bioorthogonal functional groups react in a click chemistry reaction. In some embodiments, the first and the second bioorthogonal functional group are independently selected from the group consisting of azide, dibenzocyclooctyne (DBCO), transcyclooctene, tetrazine and norbornene and variants thereof. In some embodiments, the first and the second bioorthogonal functional group is tetrazine or norbornene. In some embodiments, the hydrogel or cryogel comprises a crosslinked hyaluronic acid (HA); wherein the HA comprises a first HA and a second HA; and wherein the first HA is functionalize with a tetrazine and the second HA is functionalized with a norbornene. In some embodiments, the scaffold is macroporous. In some embodiments, the scaffold comprises pores having a diameter of about 50 microns to about 150 microns, about 80 microns to about 180 microns, or about 40 microns to about 90 microns. In some embodiments, the scaffold composition comprises a cryogel with interconnected pores. For example, the average pore size range was between about 10 µm to about 500µm, about 20 µm to about 300µm, about 80 µm to about 180µm, or about 40 µm to about 90µm. In some embodiments, the average surface pore size of HA cryogels, for example, measured by scanning electron microscopy (SEM), is about 10µm, about 20µm, about 30µm, about 40µm, about 50µm, about 60µm, about 70µm, about 80µm, about 90µm, about 100µm, about 110µm, about 120µm, about 130µm, about 140µm, about 150µm, about 160µm, about 170µm, about 180µm, about 190µm, about 200µm, about 210µm, about 220µm, about 230µm, about 240µm, about 250µm, about 260µm, about 270µm, about 280µm, about 290µm, about 300µm, about 310µm, about 320µm, about 330µm, about 340µm, about 350µm, about 360µm, about 370µm, about 380µm, about 390µm, about 400µm, about 410µm, about 420µm, about 430µm, about 440µm, about 450µm, about 460µm, about 470µm, about 480µm, about 490µm, or about 500µm. In some embodiments, the composition is formulated for administration to a subject intravenously, intramuscularly, or subcutaneously. In some embodiments, the composition is formulated for administration to a subject via injection. In some embodiments, the injection is intravenous, intramuscular, intraarterial, intrathecal, intraventricular, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, intracerebral, or intrasternal. III. METHODS The present invention features methods of delivering an active agent to a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, e.g., neutrophils, the method comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby delivering the active agent to the subject. The present invention also provides methods of modulating the activity of an innate leukocyte, restoring levels of functional innate leukocytes, e.g., neutrophils, reconstituting the levels of functional innate leukocytes and/or enhancing the regeneration of functional innate leukocytes in a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, the method comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby modulating the activity of an innate leukocyte, reconstituting the levels of innate leukocyte and/or enhancing the regeneration of an innate leukocyte in the subject. In another aspect, the present invention provides methods of enhancing the immunity of a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, e.g., neutrophils, the method comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby enhancing the immunity of the subject. In another aspect, the present invention provides methods of treating or preventing a disorder in a subject, wherein the disorder is caused by and/or is associated with a deficiency in an innate leukocyte, comprising: administering to a subject having a deficiency in an innate leukocyte or at risk of developing a deficiency in an innate leukocyte a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby treating or preventing the disorder in the subject. In another aspect, the present invention provides methods of treating or preventing a neutropenia in a subject, comprising: administering to a subject having a neutropenia or at risk of developing a neutropenia a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent, thereby treating or preventing the neutropenia in the subject. In another aspect, the present invention provides methods of a cancer in a subject, comprising (i) selecting the subject if a predetermined level of an innate leukocyte is present in the subject; (ii) administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent; (iii) determining a level of the innate leukocyte in the subject following administration of the scaffold composition; and (iv) administering a myelosuppressive therapy to the subject if the level of the innate leukocyte in the subject has attained a reference level following administration of the composition. In another aspect, the present invention provides methods of immune-responsive degradation of a scaffold, monitoring immune recovery, and/or innate leukocyte functionality in a subject suffering from depleted or reduced innate leukocytes, comprising (i) selecting a subject if a predetermined level of an innate leukocyte is present in the subject; (ii) administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof and an active agent; and (iii) determining a level of a detectable agent encapsulated in the scaffold following administration of the composition, thereby monitoring immune-responsive degradation of the scaffold, immune recovery and/or innate leukocyte functionality in the subject. In another aspect, the present invention provides a method for detecting immune recovery in a subject having a deficiency in levels of functional innate leukocytes, e.g., neutrophils, comprising: administering to the subject a scaffold composition comprising a hyaluronic acid, a hyaluronic acid derivative, or a combination thereof, assessing the level of degradation of the scaffold composition, wherein degradation of the scaffold composition is indicative of immune recovery in the subject. In various embodiments of the methods described herein, the scaffold composition further comprises an active agent. In some embodiments, the method provides for controlled, sustained, and/or delayed release of the active agent upon administration to the subject. In certain embodiments, the active agent (i) modulates the activity of an innate leukocyte; (ii) restores levels of functional innate leukocytes, e.g., neutrophils; (iii) reconstitutes levels of functional innate leukocytes; (iv) enhances the regeneration of functional innate leukocytes in the subject; (v) enhances immunity of the subject in need thereof; and/or (vi) treats or prevents a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes. In some embodiments, the active agent comprises an amino acid, a peptide, a protein, a nucleic acid, an oligonucleotide, a small molecule, or a combination thereof. In some embodiments, the active agent comprises a protein, optionally, wherein the protein is an isolated protein and/or a recombinant protein. In some embodiments, the active agent comprises a cytokine, a chemokine, and/or a growth factor. In some embodiments, the active agent comprises a cytokine, optionally, a pro-inflammatory cytokine and/or an anti- inflammatory cytokine. In some embodiments, the active agent is selected from the group consisting of a granulocyte colony stimulating factor (G-CSF), a granulocyte-macrophage colony-stimulating factor (GM-CSF), a bone morphogenetic protein 2 (BMP2), a stromal cell-derived factor (SDF), a platelet activating factor (PAF), a tumor necrosis factor α (TNFα), an interleukin-1 (IL-1), an interleukin-1α (IL-1α), an interleukin-1β (IL-1β), an interleukin-2 (IL-2), an interleukin-3 (IL-3), an interleukin-4 (IL-4), an interleukin-5 (IL-5), an interleukin- 6 (IL-6), an interleukin-7 (IL-7), an interleukin-8 (IL-8), an interleukin-9 (IL-9), an interleukin-10 (IL-10), an interleukin-11 (IL-11), an interleukin-12 (IL-12), an interleukin-13 (IL-13), an interleukin-14 (IL-14), an interleukin-15 (IL-15), an interleukin-16 (IL-16), an interleukin-17 (IL-17), an interleukin-18 (IL-18), an interleukin-19 (IL-19), an interleukin-20 (IL-20), an interleukin-21 (IL-21), an interleukin-22 (IL-22), an interleukin-23 (IL-23), an interleukin-24 (IL-24), an interleukin-25 (IL-25), an interleukin-26 (IL-26), an interleukin-27 (IL-27), an interleukin-28 (IL-28), an interleukin-29 (IL-29), an interleukin-30 (IL-30), an interleukin-31 (IL-31), an interleukin-32 (IL-32), an interleukin-33 (IL-33), an interleukin-34 (IL-34), an interleukin-35 (IL-35), an interleukin-36 (IL-36), an interleukin-1 receptor antagonist (IL-1Ra), a growth-related gene product-α (GRO-α), a growth-related gene product-β (GRO-β), a macrophage infiltrating protein-1α (MCP-1α), a macrophage infiltrating protein-1β (MCP-1β), a cytokine-induced chemoattractant (CINC), an interferon- α (IFN-α), an interferon-β (IFN-β), an interferon-γ (IFN-γ), a Fas ligand (FasL), a CD30 ligand (CD30L), a vascular endothelial growth factor (VEGF), a hepatocyte frowth factor (HGF), a transforming growth factor alpha (TGF-α), an oncostain (OSM), a neurotrophin, a monocyte chemoattractant protein-1 (MCP-1), a stem cell factor (SCF), a complement 5a (C5a), and an erythropoietin (EPO). In some embodiments, the active agent comprises a G- CSF. In some embodiments, the active agent comprises a polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF). In some embodiments, the active agent active agent is G-CSF. In various embodiments of the methods described herein, the method further comprises administering an additional active agent. In some embodiments, the additional active agent is encapsulated in the scaffold. In some embodiments, the additional active agent is administered systemically. In various embodiments of the methods described herein, the subject is or has undergone therapy that depletes or reduces the innate leukocyte in the subject. In some embodiments, the therapy is a chemotherapy or a radiotherapy for the treatment of a cancer. In various embodiments of the methods described herein, the composition further comprises a detectable agent. In some embodiments, the detectable agent is attached to the active agent. In some embodiments, the detectable agent is for detecting the scaffold and/or active agent in vivo. In some embodiments, the detectable agent is for assessing the level of degradation of the scaffold composition. In some embodiments, the detectable agent is selected from the group consisting of a dye, a fluorophore, a fluorescent compound, a luminescent compound, a chemiluminescent compound, a radioisotope, a paramagnetic metal ion, a nanoparticle, and a quantum dot, or a combination thereof. In some embodiments, the detectable agent comprises a dye. In some embodiments, the detectable agent is detectable by eye, fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), multi-mode imaging, ultrasound imaging (USI), photoacoustic imaging (PAI), and/or optical coherence tomography (OCT). In various embodiments of the methods described herein, the method further comprises assessing the level of degradation of the scaffold. In some embodiments, assessing the level of degradation of the scaffold comprises detecting the level of the detectable agent and comparing to a detectable agent reference level, optionally, wherein the detectable agent reference level is the level of the detectable agent upon administration of the scaffold composition or at an earlier time point after administration of the scaffold composition. In certain embodiments, degradation of the scaffold composition is indicative of modulation of the activity of an innate leukocyte; restoration of levels of functional innate leukocytes, e.g., neutrophils; reconstitution of levels of functional innate leukocytes; regeneration of functional innate leukocytes in the subject; enhanced immunity of the subject; and/or treatment or prevention of a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes. In certain embodiments, the method described herein may further comprise obtaining a measurement of (i) the level of the detectable agent and/or active agent in the scaffold prior to administration of the scaffold to the subject; (ii) the level of functional innate leukocytes, e.g., neutrophils in the subject prior to administration of the scaffold to the subject; (iii) the level of the innate leukocytes in the subject prior to administration of the scaffold to the subject; (iv) the level of the detectable agent and/or active agent in the scaffold after administration of the scaffold to the subject; (v) the level of functional innate leukocytes after administration of the scaffold to the subject; (vi) the level of the innate leukocytes in the subject prior to administration of the scaffold to the subject; (vii) the level of functional innate leukocytes in the subject before the subject receives a therapy that depletes or reduces the level of the innate leukocyte; and/or (viii) the level of functional innate leukocytes in the subject after the subject receives a therapy that depletes or reduces the level of the innate leukocyte. In some embodiments, the level of functional innate leukocytes, e.g., neutrophils is increased by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99% or more as compared to a reference level. In some embodiments, the level of functional innate leukocytes, e.g., neutrophils is increased by at least about 1-fold, about 2-fold, or about 3-fold or more as compared to a reference level. In some embodiments, the reference level is a standardized level. In some embodiments, the reference level is the level of functional innate leukocytes, e.g., neutrophils prior to administration of the scaffold composition or at an earlier time point after administration of the scaffold composition. In various embodiments of the methods described herein, the scaffold composition does not comprise a differentiation factor that induces the differentiation of a hematopoietic stem cell into a T cell progenitor cell. In various embodiments of the methods described herein, the scaffold composition degrades upon exposure to an enzyme produced by the innate leukocyte. In some embodiments, the scaffold composition degrades by neutrophil-mediated oxidation. In some embodiments, the degradation of the scaffold composition results in and/or enhances the release of the active agent. In some embodiments, the degradation of the scaffold composition results in and/or enhances the release of the detectable agent. In various embodiments of the methods described herein, the scaffold is macroporous or wherein the scaffold comprises pores having a diameter of about 50 microns to about 150 microns, about 80 microns to about 180 microns, or about 40 microns to about 90 microns. In various embodiments of the above aspects or any other aspect of the invention described herein, the composition is administered to the subject via injection, optionally, intravenously, intramuscularly, or subcutaneously. In various embodiments of the methods described herein, the subject is a human. In certain embodiments, the subject has a disorder selected from the group consisting of primary neutropenia, acute neutropenia, severe chronic neutropenia (SCN), severe congenital neutropenia (Kostmann's syndrome), severe infantile genetic agranulocytosis, benign neutropenia, cyclic neutropenia, chronic idiopathic neutropenia, secondary neutropenia, syndrome associated neutropenia, and immune-mediated neutropenia, chronic granulomatous disease, Chediak-Higashi syndrome, Griscelli Syndrome-II, Hermansky-Pudlak Syndrome type 2, leukocyte adhesion deficiency, specific granule deficiency, x-linked neutropenia, myeloperoxidase deficiency, and hyper-IgE syndrome. In some embodiments, the subject has a neutropenia, optionally, wherein the neutropenia is caused by or associated with radiation, alcoholism, drugs, allergic disorders, aplastic anemia, autoimmune disease, T-γ lymphoproliferative disease (T-γ LPD), myelodysplasia, myelofibrosis, dysgammaglobulinemia, paroxysmal nocturnal hemoglobinuria, cancer, vitamin B12 deficiency, folate deficiency, viral infection, bacterial infection, spleen disorder, hemodialysis, or transplantation, toxins, bone marrow failure, Schwachman-Diamond syndrome, cartilage-hair hypoplasia, dyskeratosis congenita, glycogen storage disease type IB, splenomegaly of any cause, and intrinsic defects in myeloid cells or their precursors. In some embodiments, the subject has or is receiving a hematopoietic stem cell transplantation (HSCT). In some embodiments, the administration of the composition is prior to, concurrently with, or subsequent to the HSCT. In various embodiments of the methods described herein, the method reconstitutes the innate leukocyte within 7 days, 14 days, 21 days, or 28 days. In some embodiments, the reconstitution of the innate leukocyte results in the level of innate leukocyte to be at least about 75%, 80%, 85%, 90%, 95% or 99% of a reference level. In some embodiments, the reference level is (i) a standardized level; (ii) the level of the innate leukocyte of the subject before depletion of the level of the innate leukocyte; and/or (iii) the level of the innate leukocyte of the subject before the subject receives a therapy the depletes or reduces the level of the innate leukocyte. In various embodiments of the methods described herein, the method results in (i) an increase in the number of the innate leukocytes in the subject; (ii) an increase in the number of functional innate leukocytes in the subject; (iii) a reduction in the incidence, severity, and/or duration of an opportunistic infection in the subject; (iv) a reduction in the incidence, severity, and/or duration of a symptom of neutropenia in the subject; (v) a reduction in the incidence, severity, and/or duration of a symptom of an immunodeficiency-associated complication in the subject; (vi) an increase in the level of tissue regeneration in the subject; (vii) an increase in the therapeutic efficacy of a therapy that depletes or reduces the innate leukocyte in the subject; (viii) an increase in the degradation of the scaffold in the subject; and/or (ix) an increase in the release of a detectable agent, an active agent, and/or an additional active agent from the scaffold in the subject. In various embodiments of the methods described herein, the subject has or is receiving systemic G-CSF and/or PEG-G-CSF. In some embodiments, the administration of the composition is prior to, concurrently with, or subsequent to the systemic G-CSF and/or PEG-G-CSF. In some embodiments, the method further comprising administering to the subject systemic G-CSF and/or PEG-G-CSF. In some embodiments, the subject has or is at risk of developing anti-PEG antibody (APA)-mediated rapid clearance. In some embodiments, the subject has pre-existing or induced anti-PEG antibody (APA)-mediated rapid clearance. In some embodiments, the subject has failed or is at risk of failing to respond to systemic G- CSF and/or PEG-G-CSF. In another aspect, the present invention provides a method of treating a subject for cancer in need thereof, wherein the subject is undergoing chemotherapy or radiotherapy, comprising administering to a subject suffering from depleted or reduced innate leukocytes, wherein the composition comprises a biodegradable scaffold and a cytokine that enhances the generation of the innate leukocyte; assessing the levels of the innate leukocyte in the subject; administering chemotherapy or radiotherapy to the subject wherein the levels of innate leukocyte have attained a reference level following administration of the composition. In some embodiments, the innate leukocytes are neutrophils. In some embodiments, the cytokine is G-CSF. In some embodiments, the subject is suffering from depleted or reduced innate leukocytes as a result of previous exposure to chemotherapy or radiotherapy. In some embodiments, the reference level is a standardized level, optionally, (i) wherein the reference level is the level of the innate leukocyte of the subject before depletion of the level of the innate leukocyte; and or (ii) the reference level is the level of the innate leukocyte of the subject before the subject receives a therapy the depletes or reduces the level of the innate leukocyte. In various embodiments of the methods described herein, the scaffold comprises a hydrogel. In some embodiments, the scaffold comprises a cryogel. In some embodiments, the scaffold comprises pores having a diameter between about 1 µm and 100 µm. In some embodiments, the scaffold comprises a macropore. In some embodiments, the macropore has a diameter between about 50 µm and 80 µm. In still another embodiment, the scaffold includes macropores of different sizes. In various embodiments of the methods described herein, the scaffold comprises a click-hydrogel or click cryogel. In one embodiment, the scaffold comprises a click hyaluronic acid. In various embodiments of the methods described herein, the scaffold is between about 100 µm³ to about 10 cm³ in size. In one embodiment, the scaffold is between about 10 mm³ to about 100 mm³ in size. In another embodiment, the scaffold is about 30 mm³ in size. In various embodiments of the methods described herein, the active agent is present at an amount between about 1 ng to about 1000 µg. In one embodiment, the active agent is present at between about 5 ng to about 500 ng. In another embodiment, the active agent is present at between about 5 ng to about 250 ng. In yet another embodiment, the active agent is present at between about 5 ng to about 200 ng. In still another embodiment, the active agent is present at about 200 ng. In yet another embodiment, the active agent is present at about 6 ng/mm³ to about 10 ng/mm³. In yet another embodiment, the active agent is present at about 6.5 ng/mm³ to about 7.0 ng/mm³. In various embodiments of the methods described herein, the active agent retains its bioactivity for at least twelve days after the active agent is incorporated into the scaffold. In some embodiments, the active agent retains its bioactivity for at three months after the active agent is incorporated into the scaffold. IV. KITS Any of the compositions described herein may be included in a kit. In a non-limiting example, the kit includes a scaffold composition comprising hyaluronic acid and an active agent.. In some embodiments, the kit includes the composition described elsewhere herein. In a particular embodiment, the kit comprises a syringe or alternative injection device for administering the composition. In a specific embodiment, the prefilled syringe or injection device is prefilled with the composition. The kit may further include reagents or instructions for administering the composition of the present invention to a subject. It may also include one or more reagents. The components of the kits may be packaged either in aqueous media or in lyophilized form. The container means of the kits will generally include at least one vial, test tube, flask, bottle, syringe or other container means, into which a component may be placed, and preferably, suitably aliquoted. Where there are more than one component in the kit, the kit also will generally contain a second, third or other additional container into which the additional components may be separately placed. The kits may also comprise a second container means for containing a sterile, pharmaceutically acceptable buffer and/or other diluent. However, various combinations of components may be comprised in a vial. The kits of the present invention also will typically include a means for containing the compositions of the invention, e.g., the compositions for modulating immune system, and any other reagent containers in close confinement for commercial sale. When the components of the kit are provided in one and/or more liquid solutions, the liquid solution is an aqueous solution, with a sterile aqueous solution being particularly preferred. However, the components of the kit may be provided as dried powder(s). When reagents and/or components are provided as a dry powder, the powder can be reconstituted by the addition of a suitable solvent. It is envisioned that the solvent may also be provided in another container means. The present invention is further illustrated by the following examples, which should not be construed as limiting. All cited sources, for example, references, publications, databases, database entries, and art cited herein, are incorporated into this application by reference, even if not expressly stated in the citation. In case of conflicting statements of a cited source and the instant application, the statement in the instant application shall control. Section and table headings are not intended to be limiting. EXAMPLES Example 1. Immune-responsive biodegradable scaffolds for enhancing neutrophil regeneration Neutrophils are essential effector cells for mediating rapid host defense against pathogens and their deficiency in number and function is usually fatal. In hematopoietic stem cell transplantation (HSCT) and high dose chemotherapy, an extended period of neutrophil deficiency is a leading cause of morbidity and mortality and limits the intensity and frequency of the therapy. Here, the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, termed HA cryogel, with myeloid responsive degradation behavior is described. In mouse models of innate and adaptive immune deficiency, this study shows that the infiltration of functional myeloid-lineage cells is essential to mediate HA cryogel degradation. In post-HSCT mice, myeloid-lineage immune cells were deficient for up to 3 weeks and delayed the degradation of HA cryogels. The study harnessed this myeloid cell-responsive degradation to sustain the release of granulocyte colony stimulating factor (G-CSF) from HA cryogels. In comparison to a single dose of G- CSF, sustained release from HA cryogels accelerated post-HSCT neutrophil recovery, with full recovery achieved within 14 days post-HSCT, and accelerated the rate of degradation of HA cryogels. The HA-cryogel is a potential off-the-shelf therapeutic approach for enhancing neutrophil regeneration in settings of immune deficiency and reducing the risk of immune- deficiency related complications. Introduction Neutrophils are one of the most abundant cell types of the innate immune system in mammals and mediate essential host defense against invading pathogens. Dysfunction and deficiency in their function and number underlies multidrug-resistant bacterial, fungal and viral infections in patients with immune deficiency or therapy-related neutropenia (1-3). In hematopoietic stem cell transplantation (HSCT) and high dose chemotherapy, there is a marked transient post-therapy deficiency in neutrophils in the peripheral blood, which renders patients susceptible to opportunistic infections for up to several weeks, despite the application of prophylactic antibiotics and supportive therapy (4, 5). Complications due to infection are a leading cause of morbidity and mortality, with up to 55% of patients developing post-HSCT blood-borne bacterial infections (3, 6, 7). Post-HSCT neutrophil regeneration follows successful engraftment of hematopoietic progenitors in the bone marrow (8, 9). The generation of neutrophils relies on the engraftment of adequate number of progenitors and endogenous production of granulocyte colony stimulating factor (G-CSF). G-CSF promotes neutrophil recovery by binding to its cognate receptor (G-CSFR) on hematopoietic stem cells (HSCs), activating the downstream JAK- STAT signaling through STAT3 nuclear migration, and finally contributing to granulopoiesis by promoting gene expression pertinent to cell cycle arrest, an essential prelude to myeloid differentiation (10, 11). The clinical standard for enhancing neutrophil regeneration is daily administration of recombinant human (G-CSF) or a single high dose of pegylated G-CSF (PEG G-CSF) 24 hours after the conditioning regimen (3, 12, 13). Therapy is typically discontinued after the absolute neutrophil count reaches ~ 2,000-3,000 cells/µL (14). G-CSF has a half-life of 3.5 hours and therefore the post-injection concentration in circulating blood rapidly returns to a normal homeostatic concentration. However, side effects and adverse events often pose a greater risk to patients than neutropenia (15). Repeated administration of G-CSF increases the risk of complications such a splenic rupture and capillary leak syndrome and is associated with loss of long-term repopulating activity in hematopoietic progenitors (16). Higher doses of G-CSF, required for treating chronic neutropenia, are associated with an increased risk of neoplastic disease and cancer (17). Seeking to improve the post-HSCT recovery of neutrophils and limit immune deficiency, an in vivo depot to mediate the sustained release of G-CSF and thereby enhance post-HSCT neutrophil recovery was developed. To synthesize the depot, hyaluronic acid (HA) was crosslinked using biorthogonal crosslinking and the resulting device was termed an ‘HA cryogel.’ HA was selected as it is an abundant glycosaminoglycan and a substrate for enzymatic degradation by endogenous hyaluronidases sourced, primarily by myeloid cells (18-20). The in vivo degradation kinetics was measured and the mechanism of HA cryogel degradation characterized by infiltrating immune cells in models of adaptive and innate immune depletion. The rate of infiltration of myeloid cells set the initial degradation rate of HA cryogels, which was reduced by attenuating the early myeloid cell infiltration via B cell depletion. In profoundly immune deficient mice with impaired innate immune cells, HA cryogels were not fully degraded, whereas transient post-HSCT immune depletion significantly delayed degradation of the HA cryogel until recovery of neutrophil cells (21). Since the degradation profile of HA cryogels was responsive to myeloid cell recovery, this behavior was harnessed to develop a depot to facilitate the sustained release of G-CSF. G- CSF was encapsulated in the HA cryogel and its release was mediated by polymer degradation. When administered post-HSCT, the neutrophil reconstitution in mice which received G-CSF encapsulated HA cryogels was significantly enhanced, with full recovery achieved within 14 days post-HSCT. Results A. Synthesis and characterization of HA cryogels Click-functionalized HA was prepared by conjugating either tetrazine amine or norbornene methanamine to HA using conventional carbodiimide chemistry (FIG.1A). Aqueous solutions of Tz functionalized HA (Tz-HA) and norbornene functionalized HA (Nb- HA) were then mixed in a 1:1 (v/v) ratio to allow for crosslinking (FIG.1B). The degree of crosslinking was controlled by tuning the degree of substitution (DOS) of Tz on HA. The DOS of Nb was held constant.0.6% w/v click-functionalized HA solutions were utilized to maximize polymer composition while maintaining proper viscosity to achieve mixing. The process of cryogelation, as previously described, relies on a sub-zero crosslinking environment in which the formation of ice crystals during the gelation process creates macro- porosity throughout the HA cryogels (FIG.1C) (22-24).0.8% and 7% degrees of substitution Tz-HA was synthesized and mixed with Nb-HA to make HA cryogels with different density of crosslinking. Scanning electron microscopy (SEM) of lyophilized HA cryogels was used to visualize the interconnected pore structure of HA cryogels with varying cross-linking density (FIG.1D). Average cross-sectional pore area from these SEM images was measured and it was determined that pore size was influenced by the degree of crosslinking of the HA cryogels. The average cross-sectional pore diameter was 133.0 ± 52.1 and 62.8 ± 22.7 micron on the surface HA cryogels made from 0.8% and 7% Tz-HA respectively (FIG.1). Analysis of confocal microscopy images determined that both pore morphology and relative pore size distribution are maintained after rehydration of lyophilized HA cryogels (FIGS.2A, 2B). Additionally, HA cryogels maintained shape and structure after injection through a 16-gauge needle intact. The degradation kinetics of these HA cryogels were studied in vitro using hyaluronidase-2 (HYAL2). HYAL2 degradation of HA results in cleavage of internal beta-N- acetyl-D-glucosaminidic linkages resulting in fragmenting on the HA cryogels throughout the degradation process (25). To quantify degradation, a fluorescent tag, Cy5, was covalently conjugated to HA cryogels made from 0.8% and 7% DOS Tz-HA (FIGS.3A, 3B). In vitro degradation of Cy5 labeled HA cryogels (Cy5-HA cryogels) indicated that there was a strong correlation between crosslinking density and degradation kinetics as the Cy5-HA cryogels synthesized with 7% DOS Tz-HA took longer to degrade (FIG.3C). Next, Cy5-HA cryogels were injected into the subcutaneous space of mice and degradation was tracked using in vivo imaging system (IVIS) fluorescence spectroscopy (FIG.3D). Notably, the degree of cross- linking did not influence HA degradation kinetics as HA cryogels made from 0.8% and 7% DOS Tz-HA degraded at the same rate (FIG.3E). As a result of these initial degradation studies, all further studies were conducted with 7% DOS Tz-HA. B. Depletion of immune cell subsets affects cellular infiltration into HA cryogels As the pre-conditioning regimen for bone marrow transplantation depletes all immune cell lineages, a comparison of the effect of depleting one or more lineages of immune cells on the degradation kinetics of HA cryogels was made (FIG.3A). Cy5-HA cryogels were injected into the subcutaneous space of untreated mice (FIG.4A) and the degradation kinetics were compared to degradation in mouse models of T-cell depletion (FIG.4B), B-cell depletion (FIG.4C), macrophage depletion (FIG.4D), and the immune deficient NSG mouse strain (FIG.4E). In immune competent mice, HA cryogel half-life, quantified as the time to achieve a 50% reduction in fluorescence intensity, was 9 ± 2 days (FIG.4A). The half-life in the macrophage and T-cell deficient mice were 8 ± 1 days and 10 ± 3 days respectively (FIGS.4B, 4C). The initial degradation rate of Cy5-HA cryogels in B-cell deficient mice was slowed and the half-life was 20 ± 5 days (FIG.4D). However, full degradation of the Cy5-HA cryogels was consistently achieved within 6 weeks. In contrast, there was only a 35% decrease in Cy5 signal intensity after 100 days in the NSG mice (FIG. 4E), indicating that the HA cryogel had degraded minimally. To characterize degradation, HA cryogels were explanted from mice at one, five, and ten days post-administration for haemotoxylin and eosin (H&E) staining (FIG.4F). In all groups, there was a dense accumulation of mononuclear cells along the perimeter of the HA cryogels, one day post-injection. Analysis of microscopy images showed that there was greater mononuclear cell density both within 50 microns of the outer edge and on the interior of HA cryogels removed 1-day post-injection as compared to HA cryogels removed 5 days and 10 days post-injection. Cell density on the outer 50 microns of the HA cryogel decreased 11.8-, 2.5-, 5.5-, and 7.7-fold from days 1 to days 10 in untreated, T-cell depleted, B-cell depleted, and macrophage depleted mice, respectively. Over the same time period cell density on the interior of the HA cryogels decreased 3.5-, 3.7-, 3.0, and 5.7-fold in untreated, T-cell depleted, B-cell depleted, and macrophage depleted mice, respectively (FIG.4G). To characterize the cellular components of the immune system driving HA cryogel degradation, the innate immune cell composition of the HA cryogels one and ten days after subcutaneous injection was assessed using flow cytometry in the different models of immune depletion (FIGS.5A, 6B, 7B). The infiltration of CD45⁺CD11b⁺ myeloid cells into HA cryogels one day post-HSCT, was similar in the untreated (1.7 x 10⁵ ± 5.7 x 10⁴ cells), T-cell depleted (1.8 x 10⁵ ± 4 x 10⁴ cells), and macrophage depleted mice (1.5 x 10⁵ ± 1.2 x 10⁵ cells). The infiltration of CD45⁺CD11b⁺ myeloid cells was approximately 60% lower (6 x 10⁴ ± 4 x 10⁴ cells) in the B-cell depleted mice. After ten days post-HSCT, the number of CD45⁺CD11b⁺ myeloid cells within the HA cryogels in the immune competent and T-cell depleted mice increased 3.2-fold (5.4 x 10⁵ ± 3.3 x 10⁵ cells ) and 3.5-fold (6.3 x 10⁵ ± 2.8 x 10⁵ cells) respectively whereas the CD45⁺CD11b⁺ myeloid infiltration in B-cell depleted mice was unchanged (5.8 x 10⁴ ± 2.6 x 10⁴ cells). The CD45⁺CD11b⁺ myeloid infiltration in macrophage depleted mice had decreased 67% to 4.9 x 10⁴ ± 3.8 x 10⁴ cells (FIG.5C). The kinetics of CD45⁺CD11b⁺F4-80⁺ macrophage infiltration was similar to that of CD45⁺CD11b⁺ myeloid cells in the immune competent and T-cell depleted mice. After one day post-HSCT, 6.6 x 10⁴ ± 2.7 x 10⁴ infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophages in the HA cryogels in the untreated mice and 7.7 x 10⁴ ± 8.0 x 10³ cells within HA cryogels in the T-cell depleted mice. After ten days, CD45⁺CD11b⁺ F4-80⁺ macrophage infiltration had increased 2.7-fold to 1.8 x 10⁵ ± 1.2 x 10⁵ cells in the immune competent mice and 3.5-fold to 2.7 x 10⁵ ± 1.2 x 10⁵ cells in the T-cell depleted mice. In contrast, the B-cell depleted mice had 2.4 x 10⁴ ± 1.3 x 10⁴ infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophages with HA cryogels, a similar number of infiltrating cells when compared to the immune competent and T-cell depleted mice, but had only increased 45% to 3.5 x 10⁴ ± 1.3 x 10⁴ infiltrating cells by day ten. The CD45⁺CD11b⁺ F4-80⁺ macrophage depleted mice had few infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophages, with 92% less than untreated mice with 5.2 x 10³ ± 4.4 x 10³ infiltrating cells after one day which increased 2.3-fold to 1.2 x 10⁴ ± 6.2 x 10³ cells after ten days (FIG.5D). CD45⁺CD11b⁺ F4-80⁺ macrophage polarization in the HA cryogel was quantified by comparing CD45⁺CD11b⁺F4-80⁺CD80⁺CD86⁺CD206- pro-inflammatory and CD45⁺CD11b⁺F4-80⁺CD80-CD86-CD206⁺ anti-inflammatory macrophages.1-day post- HSCT, a higher M1:M2 ratio in the T-cell depleted (7.4:1) and B-cell depleted mice (4.1:1) was quantified compared with the untreated mice (2.6:1). At day ten, the M1:M2 ratio was approximately 1:1 in all the groups (FIG.7). Taken together, these results suggest that B cells but not T cells may play a role in myeloid infiltration into HA gels, corresponding with a slowed gel degradation under B cell depletion. Further, HA cryogel degradation is delayed all together in absence of innate immune response. C. Degradation of HA cryogels is delayed during BMT model of transient immunodeficiency WThe degradation of HA cryogels in a HSCT model of transient innate and adaptive immunodeficiency was quantified. Mice received lethal total-body irradiation (L-TBI) 48 hours prior to i.v. injection of lineage depleted hematopoietic stem cells (2 x 10⁵ cells; 87.5% depleted; FIG.8A) isolated from bone marrow of syngeneic donor mice concurrent to subcutaneous HA cryogel administration (FIG.6A). Cy5-tagged HA cryogels were used to track degradation in mice that received L-TBI/HSCT and degradation rate was compared to non-irradiated control mice (FIG.6B). In contrast to non-irradiated mice, the fluorescence intensity was constant until day 20 in post-BMT mice, after which the HA cryogel proceeded to degrade at a rate comparable to that in non-irradiated mice. At day 28, the fluorescence signal decreased to 50% of the initial intensity in post-BMT mice. In the non-irradiated mice, a comparable decrease was achieved by day 11 (FIG.6C). Peripheral CD45⁺ CD11b⁺ myeloid cells were quantified to measure the rate of reconstitution of myeloid lineage cells (FIG.6D). Concurrently, to quantify CD45⁺ CD11b⁺ myeloid cell-mediated degradation, HA cryogels were excised at days 5, 16, and 21 and analyzed via flow cytometry. In non- irradiated mice, 5 days after HA cryogel administration the CD45⁺ CD11b⁺ myeloid cell infiltration was about 5.2 x 10⁵ ± 1.7 x 10⁵ cells whereas in post-BMT mice, 5 days after HA cryogel implant there was 1% (5.1 x 10³ ± 3.6 x 10³) as many CD45⁺ CD11b⁺ myeloid cells. 21 days post-BMT, the number of infiltrating CD45⁺ CD11b⁺ myeloid cells in excised HA cryogels had increased by 68.6-fold to a comparable 3.5 x 10⁵ ± 2.5 x 10⁵ cells. (FIG.6E). CD45⁺ CD11b⁺ F4-80⁺ macrophage infiltration into HA cryogels was delayed in the mice that received a BMT. 5 days after HA cryogel administration, the number of infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophage cells in excised HA cryogels from the non-irradiated mice was 1.4 x 10⁵ ± 2.1 x 10⁴. In post-HSCT mice, 5.1 x 10³ ± 3.6 x 10³ infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophage cells (96% decrease) were quantified in excised HA cryogels 5 days after administration. In contrast to myeloid infiltration at day 21, number of infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophage cells had not yet recovered and was 85% less (2.1 x 10⁴ ± 1.7 x 10⁴ cells) when compared to non-irradiated, day 5 infiltrating CD45⁺CD11b⁺ F4-80⁺ macrophage cells (FIG.6F). At day 17 post- HSCT neutrophils constituted 94.8 ± 2.2% of myeloid cells in post-HSCT mice (FIG.8B). This data indicates that irradiation reduces myeloid infiltration into HA cryogels and extends their persistence. D. Enhanced reconstitution of peripheral blood neutrophils WNext, the HA cryogel was developed as a depot for mediating the sustained release of G-CSF and enhance CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil recovery in mice after syngeneic HSCT (FIG.9A). CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil cells were quantified by flow cytometry analysis of peripheral blood. CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil reconstitution was enhanced in mice that received either bolus IP injection of 2 μg PEG G- CSF or administration of two HA cryogels containing 1 μg of G-CSF each as compared to mice that received either bolus IP injection of 2 μg of G-CSF or untreated mice (FIG.9B). At day 7 post-HSCT, mice that received bolus PEG G-CSF and G-CSF encapsulated within HA cryogels had recovered 6.3 ± 1.1% and 6.4 ± 0.7% of neutrophils respectively whereas the mice that received bolus G-CSF and untreated had recovered 3.5 ± 0.6% and 3.9 ± 1.3%, respectively (FIG.9C). At day 12, PEG G-CSF treated mice recovered 54.1 ± 18.0% of neutrophils, and mice treated with G-CSF encapsulated in HA cryogels recovered 50.0 ± 14.6% of neutrophils, whereas neutrophil recovery in the bolus G-CSF treated group was only 24.1 ± 10.9%, and the untreated group, 26.9 ± 8.2% (FIG.9D). Repeated IP administration of 100 ng of G-CSF twice per day resulted in substantial morbidity in mice, consistent with previous reports (FIG.10A) (26). The experiment was continued until day 28, but by day 17 the peripheral blood CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophil concentration had recovered in all experimental groups and there was no statistical difference between the different experimental groups (FIG.10B). The degradation of blank and G-CSF- loaded Cy5-tagged HA cryogels in live mice was quantified using in vivo imaging. The enhanced reconstitution of CD45⁺CD11b⁺CD115-Ly6-G⁺ neutrophils in mice that received HA cryogels with G-CSF lead corresponded to accelerated degradation of the Cy5-HA cryogels as measured by attenuation of fluorescence intensity (FIG.9E). These results suggest that G-CSF release from a HA cryogel can improve neutrophil recovery in lethally radiated mice comparable to a clinical standard therapy, and that gel degradation may be used as an indicator of neutrophil recovery. Summary As described in this example, a macroporous HA cryogel-based device was developed whose degradation is mediated by innate immune recovery to provide sustained release of G- CSF following HSCT to accelerate neutrophil recovery. Harnessing post-HSCT regeneration of myeloid lineage cells to initiate biomaterials clearance is distinct conceptually from other methods of drug delivery in settings of immune deficiency. The release of G-CSF from the HA cryogel accelerates myeloid reconstitution which, in turn, accelerates the degradation of the device. This positive feedback loop can be monitored by fluorescently tagging the HA cryogel, thereby allowing this device also to track myeloid reconstitution and functionality in a non-invasive manner. These features address shortcomings of current delivery methods of G-CSF which require daily administrations. HA was chosen as the backbone of this device as it is ubiquitous in the extracellular matrix and has an extensive history of clinical use as a biomaterial in both biomedical and cosmetic applications (27-32). The process of cryogelation was utilized during the cross- linking process in order to provide enhanced mechanical stability and provide shape memory properties upon injection (33, 34). In contrast, other degradable polymers such as poly (lactic-co-glycolic acid) or oxidized alginate typically degrade by hydrolysis, independent of myeloid lineage functionality (35-38). Tz and Nb click-chemistry was used as the functional groups are biorthogonal and the reaction proceeds without the need for addition of external energy, such as by increasing temperature, or catalysts (39, 40). This was an important consideration as other common cross-linking strategies directly target the carboxylic acid or hydroxyl side chains of the HA polymer and the unreacted cross-linking agent may affect the bioactivity of encapsulated proteins (41-44). To characterize the effect of cross-linking density on HA cryogel degradation, a polymer mixture was formulated in which the DOS of Nb was greater than that of Tz. Through this approach the cross-linking density was modified by changing the DOS of Tz on HA prior to cryogelation. Initial studies characterizing in vitro degradation indicated that HA cryogels made with lower DOS of Tz-HA would degrade faster. This is consistent with previous reports and indicated that varying the DOS of Tz-HA would influence the cross- linking density of the HA cryogels (25, 45). However, in vivo, there was no difference in the rate of degradation of the same HA cryogels, suggesting that immune clearance by infiltrating myeloid cells, rather than cleavage by enzymatic degradation, is rate limiting. While it is well-established that immune deficiency impacts the foreign body response to implanted biomaterials, it was unclear how this deficiency might impact the rate of their degradation (5, 46). In mouse models of innate and adaptive immune deficiency, it was observed that the number of infiltrating myeloid lineage cells within the HA cryogels at days 1 and 10 were 63% and 89% lower in the B-cell depleted mice than compared to the untreated mice, which is consistent with prior literature (46). Macrophage depletion did not affect the number of infiltrating myeloid cells at day 1, but by day 10 the absolute number of infiltrating cells was 92% lower than the untreated group. Notably, the initial degradation kinetics of HA cryogels in B-cell depleted mice was slowed and there was no difference in HA degradation in the macrophage depleted mice than compared to the untreated controls. This suggests that the acute phase of the foreign body response, mediated by neutrophils and monocytes, is important in the initial phase of degradation. Though, in all lineage depletion models HA cryogels were cleared over the course of 5 weeks, indicating that in the B-cell depletion model the acute phase of the foreign body response is impaired but still functional. The importance of myeloid infiltration in eliciting HA cryogel degradation was further supported by studies in NSG mice, in which the HA cryogels did not degrade appreciably even after 3 months. These results were expanded upon by characterizing HA cryogel degradation in HSCT models of transient immune deficiency and showing that the degradation of HA cryogels was absent until recovery of peripheral myeloid lineage counts and infiltration of myeloid lineage cells into the HA cryogels. The delivery of HA cryogels in vivo mediated the sustained release of bioactive G- CSF and enhanced post-HSCT neutrophil recovery. These studies indicated that the recovery rate of neutrophils was significantly enhanced in mice that received HA cryogels loaded with G-CSF compared with mice who received bolus G-CSF and untreated mice. As the half-life of G-CSF is 3.5 hours, it is expected that bolus G-CSF would not affect neutrophil recovery rate as compared to the untreated control. PEG G-CSF, which has a longer half-life of 42 hours, is used clinically to overcome this limitation (47, 48). In these studies, the effects of PEG G-CSF and G-CSF release from HA cryogel on neutrophil reconstitution rate were similar. Further, since the HA cryogel is degraded after myeloid recovery, G-CSF concentrations in the periphery would reduce to homeostatic concentrations rapidly after recovery. This strategy contrasts with sustained release PEG G-CSF, which is associated with hyperleukocytosis and cytokine release syndrome, leading to tissue damage and capillary leak syndrome in some patients (16, 49). It is recognized that therapy-induced immune deficiency substantially limits the applicability of front-line chemo- and immunotherapies in patients, and dysregulation is associated with the manifestation of opportunistic infections. Collectively, these findings suggest that the HA cryogel represents a simple-to-administer and safe system that can enhance neutrophil regeneration in myelosuppressive treatments, such as HSCT, with neutropenia as a side-effect and thereby improve treatment outcomes in bone marrow transplant and other cancer therapies. Materials and Methods The following Materials and Methods were used in Example 1. General methods and statistics Sample sizes for animal studies were based on prior work without use of additional statistical estimations. Results were analyzed by one-way ANOVA with a Tukey post hoc test using GraphPad Prism software. Where ANOVA was used, variance between groups was found to be similar by Bartlett’s test. Alphanumeric coding was used in blinding for pathology samples and cell counting. Materials 2MDa molecular weight (MW) sodium hyaluronate was purchased from Arcos Organics; 2-morpholinoethanesulfonic acid (MES), sodium chloride (NaCl), sodium hydroxide (NaOH), N-hydroxysuccinimide (NHS), and 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide hydrochloride (EDC) were purchased from Sigma-Aldrich. (4-(1,2,4,5-tetrzain- 3-yl)phenyl)methanamine (tetrazine amine) was purchased from Kerafast.1- bicyclo[2.2.1]hept-5-en-2-ylmethanamine (norbornene amine) was purchased from Matrix Scientific. Cy5-tetrazine amine was purchased from Click Chemistry Tools. Click functionalization of HA Tetrazine functionalized HA (Tz-HA) or norbornene functionalized HA (Nb-HA) were prepared by reacting tetrazine amine or norbornene amine to HA using EDC/NHS carbodiimide chemistry. Sodium hyaluronate was dissolved in a buffer solution (0.2% wt/vol, pH ~ 6.5) of 100mM MES buffer. NHS and EDC were added to the mixture to active the carboxylic acid groups on the HA backbone followed by either tetrazine amine or norbornene amine (molar ratio of NHS:EDC:tetrazine amine = 5:5:1 and molar ratio of NHS:EDC:norbornene amine = 5:5:1). The solution was stirred at room temperature for 24 hours and transferred to a 12,000Da MW cutoff dialysis sack (Sigma Aldrich) and dialyzed in 4L of NaCl solutions of decreasing molarity (0.125M, 0.100M, 0.075M, 0.050M, 0.025M, 0M, 0M, 0M, 0M) for 8 hours per solution. After dialysis, solutions containing Tz-HA or Nb- HA were frozen overnight and lyophilized (Labconco Freezone 4.5) for 48 hours. Cy5 conjugated Nb-HA was synthesized following a previously described technique with some modifications.0.8mg of cy5-tetrazine was reacted with 100mg of Nb-HA at 0.2 wt/vol in DI water for 24 hours at 37 ºC and purified by dialysis in DI water using a 12,000Da MW cutoff dialysis sack for 48 hours. Dialysis water bath was changed once every 8 hours. Cy5 conjugated Nb-HA was then frozen overnight and lyophilized for 48 hours. HA cryogel fabrication and pore quantification HA cryogels were made following a previously described technique with some modifications(24) . Aqueous solutions of 0.6% wt/vol Tz-HA and Nb-HA were prepared by dissolving lyophilized polymers into deionized water. Aqueous Tz-HA and Nb-HA solutions were mixed at a 1:1 volume ratio, pipetted into 30μL Teflon molds, and transferred to a -20 ºC freezer to allow for overnight cryogelation. Synthesis of cy5-HA cryogels follows the same protocol as above, except substituting cy5 conjugated Nb-HA for Nb-HA. For scanning electron microscopy (SEM), frozen HA cryogels were lyophilized for 24 hours. Lyophilized HA cryogels were collected in Petri dishes and adhered onto sample stubs using carbon table and coated with iridium in a sputter coater. Samples were imaged using secondary electron detection on a FEI Quanta 250 field emission SEM. Fluorescence images of cy5-HA cryogels were acquired using an Upright Zeiss LSM 710. Pore size quantification of SEM images and relative distribution of pore sizes of confocal images was doing using FIJI image processing package (50). For biological assays, cryogels were thawed and collected in Petri dishes. Bone marrow transplantation, lineage depletion, and blood analysis All animal work was approved by the UCSD Institutional Animal Care and Use Committee (IACUC) and followed the National Institutes of Health guidelines and relevant ethical regulations. C57BL/6 (B6, H-2^b) and NSG mice (Jackson Laboratories) were female and between 6 and 8 weeks old at the start of the experiments. All mice in each experiment were age matched and no randomization was performed. The pre-established criteria for animal omission were failure to inject the desired cell dose in transplanted mice and death due to transplant failure. Health concerns unrelated to the procedure (for example, malocclusion, severe dermatitis) were criteria for omission and euthanasia. Immune cell lineage depletion models B-cell lineage depletion in B6 mice was induced using anti-mouse B220/CD45R antibodies (RA3.31/6.1, Bio X Cell). T-cell lineage depletion in B6 mice was induced using anti-mouse CD4 antibodies (GK1.5, Bio X Cell) and anti-mouse CD8α antibodies (2.43, Bio X Cell). Macrophage depletion in B6 mice was induced by clodronate liposomes (Liposoma). For all lineage depletion models, mice received intraperitoneal injections of 0.1mL (400μg) of antibodies or 0.1mL of clodronate liposome solution 3 days before subcutaneous HA cryogel or cy5-HA cryogel injection. Antibodies or clodronate liposomes were administered twice per week until complete gel degradation or until mice were euthanized and gels removed for further analysis. Transplant models All total-body irradiation experiments were performed with a cesium-137 gamma- radiation source: SL: TBI (B6 recipients) with one dose of 2 x 10⁵ lineage-depleted bone marrow cells from B6 mice. Bone marrow cells for transplantation or analysis were harvested by crushing all limps. Crushed tissue and cells were filtered through a 70μm mesh. A single- cell suspension was prepared by passing the cells once through a 20-gauge needle. Total cellularity was determined by counting cells using a hemacytometer. Bone marrow cells were depleted of mature immune cells (expressing CD3ε, CD45R/B220, Ter-119, CD11b, or Gr-1) by magnetic selection (BD Biosciences). Cells were incubated with a mix of Pacific Blue- conjugated lineage specific antibodies (antibodies to CD3, NK1.1, Gr-1, CD11b, CD19, CD4 and CD8) and with Sca-1 and cKit-specific antibodies. Hematopoietic stem cells (Lin-Sca- 1^hic-kit^hi) were isolated using a FACSAria cell sorter (BD). Sorted cells were ≥ 87% pure. Lineage-depleted bone marrow cells were suspended in 100μL of sterile 1x PBS and administered to mice via a single i.v. injection. While mice were anesthetized, received a subcutaneous injection of a single HA cryogel or cy5-HA cryogel, which was suspended in 200μL of sterile 1x PBS, into the dorsal flank by means of a 16-gauge needle. The site of injection was shaved and wiped with a sterile alcohol pad prior to gel injection. In vitro degradation Cy5-HA cryogels synthesized with 0.2%, 0.8%, and 7% DOS Tz-HA and placed into individual 1.5mL microcentrifuge tubes (Thermo Scientific) with 1mL of 100U/mL HYAL2 (Sigma Aldrich) in 1x PBS. Degradation studies were conducted in tissue culture incubators at 37 ºC. Supernatant from samples were collected every 24 – 72 hours by centrifuging the samples at room temperature at 2,000G for 5 minutes and removing 0.9mL of supernatant. Cy5-HA cryogels were resuspended by adding 0.9mL of freshly made 100U/mL HYAL2 in 1x PBS. Fluorescence measurements were conducted using a Nanodrop 2000 Spectrophotometer (Thermo Fisher Scientific) and these values were normalized to sum of the fluorescence values over the course of the experiment. In vivo degradation In vivo HA cryogel degradation was performed with cy5-HA cryogels synthesized with 0.2%, 0.8%, and 7% DOS Tz-HA in immune competent B6 mice and with cy5-HA cryogels synthesized with 7% DOS Tz-HA in immune competent mice B6 mice, immunodeficient B6 mice, and NSG mice. In all cases, a single cy5-HA cryogel is administered into the dorsal flank of an anesthetized mouse and the fluorescent intensity of the cy5-HA cryogel was quantified using an IVIS spectrometer (PerkinElmer) at predetermined timepoints and analyzed using LivingImage software (PerkinElmer). At each timepoint, mice were anesthetized and the area around the subcutaneous cy5-HA cryogel was shaved to reduce fluorescence signal attenuation. Fluorescence radiant efficiency, the ratio of fluorescence emission to excitation, was measured longitudinally as a metric to quantify fluorescence from subcutaneous cy5-HA cryogels. These values were normalized to the to the measured initial value at day 3. Day 3 was chosen as the initial timepoint because swelling at the injection site on previous days causes significant fluorescent signal attenuation. Flow cytometry analysis Anti-mouse antibodies to CD45 (30-F11), CD11b (M1/70), CD4 (RM4-5), CD8α (53- 6.7), B220 (RA3-6B2), CD80 (16-10A1), CD206 (C068C2), Ly6-G/Gr-1 (1A8), lineage cocktail (17A2/RB6-8C5/RA3-6B2/Ter-119/M1/70), Ly-6A/E/Sca-1 (D7), and CD117/cKit (2B8) were purchased from Biolegend. Anti-mouse F4/80 (BM8) and CD86 (B7-2) were purchased from eBioscience. All cells were gated based on forward and side scatter characteristics to limit debris, including dead cells. Antibodies were diluted according to the manufacturer’s suggestions. Cells were gated based on fluorescence-minus-one controls, and the frequencies of cells staining positive for each marker were recorded. To quantify T-, B- and myeloid cells in peripheral blood, blood was first collected from the tail vein of mice into EDTA coated tubes (BD). Samples then underwent lysis of red blood cells and were stained with appropriate antibodies corresponding to cell populations of interest. To quantify infiltrating immune cells within HA cryogels, mice were sacrificed, gels removed, and HA cryogels crushed against a 70-micron filter screen before antibody staining. Absolute numbers of cells were calculated using flow cytometry frequency. Flow cytometry was analyzed using FlowJo (BD) software. Histology After euthanasia, HA cryogels were explanted and fixed in 4% paraformaldehyde (PFA) for 24 hours. The fixed HA cryogels were then transferred to 70% ethanol solution and embedded in paraffin wax. Sections (5μm) of the samples were stained with routine H&E stain. Quantification of histology slides Digital copies of H&E slides were made using an Aperio AT2. Digital slides were rendered in ImageScope and the positive pixel algorithm was used to quantify pixels associated with cell nuclei. The average number of pixels per cell nuclei was determined to be ~55. 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Biomaterials. 2005;26(4):359-71. 46. Doloff JC, Veiseh O, Vegas AJ, Tam HH, Farah S, Ma M, et al. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nature materials.2017;16(6):671-80. Epub 2017/03/21. 47. Ashrafi F, Salmasi M. Comparison of the effects of pegylated granulocyte-colony stimulating factor and granulocyte-colony stimulating factor on cytopenia induced by dose- dense chemotherapy in breast cancer patients. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.2018;23:73. Epub 2018/09/06. 48. Molineux G. The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Current pharmaceutical design.2004;10(11):1235-44. Epub 2004/04/14. 49. Usami E, Kimura M, Iwai M, Go M, Asano H, Takenaka S, et al. The incidence and timing of leukocyte overshoot after pegfilgrastim administration. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.2019;25(4):869-74. Epub 2018/04/14. 50. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nature Methods.2012;9(7):676- 82. Example 2. Further characterization of Immune-responsive biodegradable scaffolds for enhancing neutrophil regeneration Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)- based scaffold, termed HA cryogel, with myeloid responsive degradation behavior is reported. In mouse models of immune deficiency, it is shown that the infiltration of functional myeloid-lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post-HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. The neutrophil-responsive degradation was harnessed to sustain the release of granulocyte colony stimulating factor (G-CSF) from HA cryogels. In comparison to a single dose of G-CSF, sustained release from HA cryogels enhanced post-HSCT neutrophil recovery, comparable to pegylated G-CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts. Introduction Neutrophils mediate essential host defense against pathogens and are among the earliest responders in tissue injury^1-3. Neutrophil deficiency, termed neutropenia, contributes to opportunistic infections and could impair tissue regeneration in affected individuals ^4-7. In autologous hematopoietic stem cell transplantation (HSCT) pre-conditioning myelosuppressive regimens can contribute to a marked transient post-therapy impairment of neutrophils and render recipients susceptible to immune deficiency-associated complications for up to several weeks ^{6, 8-11}. Post-HSCT neutrophil regeneration follows successful bone marrow engraftment of transplanted hematopoietic cells ^{12, 13}, facilitated by granulocyte colony stimulating factor (G- CSF)-mediated granulopoiesis of hematopoietic cells ^14-16. Neutropenia is typically treated as an emergency and, in a subset of patients, the risk of neutropenia may be prophylactically addressed with post-HSCT subcutaneous injection of recombinant human G-CSF (filgrastim) to facilitate recovery ^{6, 14, 17, 18}. Daily injections are used as G-CSF has a half-life of a 3 – 4 hours, which can be extended by conjugating G-CSF with polyethylene glycol (PEGylation) ^{19, 20}. However, immune responses against PEG have been demonstrated to enhance clearance of PEG-G-CSF in an antibody-dependent manner²¹. As multiple cycles of PEG-G-CSF treatment are common, long-term treatment could be rendered ineffective. Therefore the development of a sustained release method to deliver G-CSF while avoiding immune responses against PEG, and concurrently assess neutrophil function could greatly improve the current standard-of-care. Seeking to improve post-HSCT recovery of neutrophils and simultaneously assess recovery, a biodegradable depot was developed to prophylactically deliver G-CSF in post-HSCT recipients. The depot comprised a porous injectable scaffold made by low-temperature crosslinking, termed cryogelation, of hyaluronic acid (HA), an easily sourced and readily derivatized anionic glycosaminoglycan, termed ‘HA cryogel.’ As a component of the extracellular matrix, endogenous HA is a substrate for degradation by myeloid cells through enzymatic action and by neutrophil-mediated oxidation^22-24. Harnessing the immune-responsiveness of HA, in vivo degradation of HA cryogels in immune deficient and post-HSCT mice was characterized and myeloid cell infiltration in HA cryogels was identified to be key mediators in facilitating degradation, which was significantly reduced or altogether eliminated in mice with severely deficient neutrophil function. Transient but profound post-HSCT myeloid depletion significantly delayed degradation of HA cryogels until recovery of neutrophils ²⁵. As the degradation profile of HA cryogels was responsive to neutrophil recovery, encapsulated G-CSF was harnessed to facilitate the sustained release, which was mediated by HA cryogel degradation. Neutrophil reconstitution was enhanced in post-HSCT mice injected with GCSF-encapsulated HA cryogels, comparable to a single dose of PEGylated G-CSF, which accelerated HA cryogel degradation. Results A. Synthesis and characterization of HA cryogels Click-functionalized HA was prepared by conjugating either tetrazine amine or norbornene methylamine to HA using carbodiimide chemistry. Norbornene- functionalized HA (HA-Nb) was reacted with tetrazine (Tz)-Cy5 to form Cy5-labeled HA-Nb (Cy5-HA- Nb). Tz amine-functionalized HA (HA-Tz) was prepared at 7% degree of substitution (termed high-DOS).0.8% DOS HA-Tz (termed low DOS) was also prepared for comparison. Endotoxin levels of HA-Tz and Cy5-HA-Nb were quantified to be less than 5 endotoxin units/kg, the threshold pyrogenic dose for preclinical species²⁶ (FIG.11). To maximize polymer concentration while maintaining proper viscosity to achieve mixing, 0.6% w/v aqueous solutions of HA-Tz and Cy5-HA-Nb, pre-cooled to 4ºC, were well mixed in a 1:1 (v/v) ratio by vortexing (FIG.12A). The solution was then pipetted onto individual pre- cooled (-20ºC) cryomolds (30 µL/mold) and immediately transferred to a -20ºC freezer and allowed to freeze (Calculations), to generate Cy5-HA cryogels (FIGS.12B-12C). To characterize Cy5-HA cryogels, the swelling ratio was estimated by comparing the hydrated vs. cast volume and the aqueous mass composition from the wicked mass and fully hydrated mass. The swelling ratio was 1.5 ± 0.1 in both low- and high-DOS Cy5-HA cryogels (FIG.13A). The aqueous mass composition was 76.3 ± 4.0% and 71.9 ± 2.6% in low- and high-DOS Cy5-HA cryogels respectively (FIG.13B). To measure surface porosity of lyophilized Cy5-HA cryogels, scanning electron microscopy (SEM) was used (FIG.12D, FIG.13C). The surface pore structure images were used to measure the average pore diameter using FIJI, which were between 80-180μm and 40-90μm for low- and high-DOS Cy5-HA cryogels respectively (FIG.13D). To characterize interconnectedness of the Cy5-HA cryogel pore structure, fully hydrated low- and high-DOS Cy5-HA cryogels were incubated with Fluorescein isothiocyanate (FITC)-labeled 10μm diameter melamine resin particles and imaged using a confocal microscope (FIG.12E, FIG. 13E). Since the route of administration of the Cy5-HA cryogels is through a needle, this experiment was repeated with Cy5-HA cryogels after injection and observed similar penetration of the FITC-labeled 10μm particles (FIG.12E, FIG.13E). Image analysis of z- stacked images showed co-localization of the FITC-labeled 10μm particles with Cy5-HA up to a depth of 100μm below the surface, which was the limit of detection (FIG.13F). Both low- and high-DOS Cy5-HA cryogels maintained pore morphology and relative surface pore size distribution following lyophilization and rehydration (FIG.13G, 13H). Cy5-HA cryogels also maintained shape and structure post-injection. To confirm susceptibility of Cy5-HA cryogels to enzymatic degradation, a hyaluronidase-2 (HYAL2)-based in vitro assay was used (FIG.12F). In native HA, HYAL2 cleaves internal beta-N-acetyl-D-glucosaminidic linkages resulting in fragmentation of HA²⁷. Here, HYAL2 degraded HA cryogels and high DOS Cy5-HA cryogels degraded at a slower rate compared to the low DOS Cy5-HA cryogels in vitro (FIG.12G, FIG.14A). To confirm in vivo degradation, low- and high-DOS Cy5-HA cryogels were injected in subcutaneously in the hind flank of mice and degradation was measured using in vivo imaging system (IVIS) fluorescence spectroscopy (FIG.12H). In contrast to in vitro degradation, both low- and high-DOS Cy5-HA cryogels degraded at a similar rate (FIG.12I, FIG.14B). This observation, together with the finding of a similar pore size distribution in hydrated low- and high-DOS HA cryogels (FIG.13H), supported the selection of one of the types of HA cryogels for subsequent experiments, and high-DOS HA cryogels were selected. To characterize if HA cryogels made from different batches of derivatized HA affected in vivo degradation, degradation of Cy5-HA cryogels made from three distinct batches of Cy5-HA- Nb and HA-Tz was compared and it was confirmed that all Cy5-HA-cryogels degraded at a similar rate (FIG.14C). B. Depletion of immune cell subsets affects cellular infiltration into HA cryogels As the HSCT pre-conditioning regimen depletes all immune cell lineages, the effect of immune depletion on HA cryogel degradation was measured. Cy5-HA cryogels were subcutaneously injected into the hind flank of untreated C57Bl/6J (B6) mice (FIG.15A) and the degradation profile was compared to that in B6 mice receiving (i) anti-Ly6G antibodies and anti-rat κ immunoglobulin light chain to deplete neutrophils (FIG.15B), (ii) clodronate liposomes to deplete macrophages (FIG.15C), (iii) anti-CD4 and anti-CD8 antibodies to deplete T cells (FIG.16A), (iv) anti-B220 to deplete B-cells (FIG.16B) and immune deficient NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG) mice (FIG.15D). The durability of depletion was assessed by measuring peripheral blood cellularity throughout the duration of the degradation study (FIGS.16C-16J, FIG.11). In untreated immune competent mice, the average half-life of Cy5-HA cryogels, quantified as the time to achieve a 50% reduction in fluorescence intensity, was about 9.5 days (FIG.15A, FIG.16K). The average half-life in the macrophage, neutrophil, T cell, and B cell depleted mice was similar at about 11.8 days, 11.3 days, 9.6, and 10.2 respectively (FIGS.15B-15C, FIG.16K). In contrast, only a 35% reduction in Cy5 signal intensity was measured after 3 months in the NSG mice (FIG.15D). Retrieval of Cy5-HA cryogels from sacrificed mice at the endpoint confirmed that the gels had minimally degraded (FIG.16L). To assess cellular infiltration and the foreign body response, Cy5-HA cryogels were explanted from the above groups at 1-, 5-, and 10-days post-injection and stained using haemotoxylin and eosin (H&E). In Cy5-HA cryogels retrieved from all groups except NSG mice, the total cellularity increased from day 1 to 10 and formed a distinct capsule encapsulating the HA cryogel, indicative of a foreign body response (FIG.15E, FIG.17A). In NSG mice, some infiltrates were quantified on day 1, however there was no appreciable increase in cellularity at the later timepoints or a capsule by day 10 (FIG.15E). H&E slides were further analyzed to quantify the cell density in the different groups. Differences in infiltrates between the untreated and all immunodepleted B6 mice were significant at the earlier timepoints, and either increased or remained constant in all immunodepleted B6 (FIG. 15F, FIG.17B). In contrast, cell infiltrates in HA cryogels retrieved from NSG mice reduced steadily and were 80% lower than untreated B6 mice by day 10 (FIG.15F). To identify the immune cells contributing to HA cryogel degradation, cell infiltrates in the Cy5-HA cryogels were quantified 1- and 10- days post-injection using flow cytometry in untreated and immune depleted B6 and NSG mice (FIGS.18A-18B, FIG.19A). Viability of infiltrating cells, quantified by negative AnnexinV staining, was consistently greater than 95% in all groups (FIG.19B). Infiltration of total CD45⁺CD11b⁺ (myeloid) cells into HA cryogels of untreated B6 mice and T cell depleted B6 mice were similar after 1- and 10-days post-injection (FIG. 19C). While there were comparable myeloid cells in HA cryogels retrieved 1-day post- injection from B cell depleted B6 mice, by day 10 the number was about 66% lower than in untreated B6 mice (FIG.19C). Similarly, myeloid cell infiltration in Cy5-HA cryogels retrieved 1-day post-injection from macrophage depleted mice was unaffected, however by day ten the number of infiltrating myeloid cells was about 58% lower than untreated B6 mice (FIG.18C). Neutrophil depletion in B6 mice reduced the total number of myeloid cells in Cy5-HA cryogels compared with the untreated B6 mice by about 77% 1-day and 68% 10- days post-injection respectively (FIG.18C). In NSG mice myeloid cell infiltration in HA cryogels was 51% lower 1-day and 91% lower 10-days post-injection as compared to untreated B6 mice (FIG.18C). CD45⁺CD11b⁺F4/80⁺ (macrophage) infiltration in Cy5-HA cryogels retrieved from all groups except NSG mice reduced from 1- to 10-days (FIG.18D, FIG.19D). Intraperitoneal (i.p.) administration of clodronate liposomes minimally affected macrophage infiltration in Cy5-HA cryogels even though it was effective in depleting peripheral blood monocytes (FIG.18D, FIGS.16E-16F). In NSG mice, macrophage infiltration was 74% lower than in the untreated B6 mice on day 1 and remained unchanged 10-days post-injection (FIG.18D). In CD45⁺CD11b⁺F4/80-Ly6G⁺ (neutrophil) depleted B6 mice, an additional intracellular Ly6G staining step was included, as the method of neutrophil depletion is known to induce internalization of the Ly6G receptor (FIG.19E) ²⁸. Neutrophil infiltration in Cy5- HA cryogels retrieved from untreated B6 and T cell depleted B6 mice was comparable between 1- to 10-days post-injection (FIG.18E, FIG.19F). B cell depletion did not affect the initial neutrophil infiltration 1-day post-injection compared with untreated controls but reduced the number of infiltrating neutrophils by 10-days post-injection (FIG.19F). As expected, neutrophil depletion significantly reduced initial neutrophil infiltration, by about 97%, compared to the untreated control. In this group, neutrophils constituted less than 50% of infiltrating myeloid cells at all timepoints assessed. Despite an increase by day 10, attributable to the internalization of the Ly6G receptor which led to an approximate 4-fold increase in the infiltrating neutrophil fraction (FIG.19E), the number of infiltrating neutrophils were still 84% lower compared with untreated B6 mice (FIG.18E). Macrophage depletion did not affect the initial neutrophil infiltration 1-day post-injection compared with untreated B6 mice but reduced the number of infiltrating neutrophils by 65% compared with untreated B6 mice by day 10. HA cryogels retrieved from NSG mice had 50% fewer neutrophils than those from untreated B6 mice on day 1 and very few to none were found by day 10 post-injection (FIG.18E). In NSG mice neutrophils constituted over 90% of total myeloid cells on day 1 but decreased to about 8% by day 10 (FIG.18E). This observation along with minimal Cy5-HA cryogel degradation in NSG mice (FIG.15D), supported a key role of functional neutrophils in mediating degradation. In all groups, the infiltration of CD45⁺CD11b⁺F4/80-Ly6G-CD115⁺ (monocyte) cells were minimal and constituted a negligible portion of total infiltrating myeloid cells (FIGS.19G-19H). To provide additional confirmation of infiltrating neutrophils and macrophages, immunohistochemical (IHC) staining was used to assess for Ly6G⁺ and F4/80⁺ cells respectively in untreated B6 mice and NSG mice at 1-, 5-, and 10-days post-injection. Staining on day 1 corroborated the flow cytometry data in that there were more neutrophils than macrophages within the Cy5-HA cryogels (FIG.19H, FIG.20A). On subsequent days, non-specific debris precluded accurate assessment in Cy5-HA cryogels retrieved from B6 mice (FIG.20A). As a result of non-specific staining of debris at later timepoints, IHC was only conducted on Cy5-HA cryogels excised 1-day after injection in macrophage depleted, neutrophil depleted, T cell depleted, and B cell depleted mice. Staining of these samples confirmed the presence of both Ly6G and F4/80 in Cy5-HA cryogels confirming flow cytometry data (FIG.19H, FIG.20B). In NSG mice, IHC staining of Ly6G⁺ and F4/80⁺ cells followed the results from flow cytometry analysis. Significantly more neutrophils than macrophages in Cy5-HA cryogels were observed 1-day after injection (FIG.20C). On day 5, there were significant macrophage and neutrophil infiltrates (FIG.20C) and by day 10, the neutrophil infiltration reduced significantly as expected from flow cytometry analysis (FIG. 19G, FIG.20C). To further characterize the role of functional neutrophils, the degradation of Cy5-HA cryogels in B6 and B6.129S-Cybb^tm1Din (gp91^phox-) mice was compared. Affected hemizygous male gp91^phox- mice have a defect in the NADPH oxidase enzyme, which renders mice deficient in neutrophil function through the production of reactive oxygen species ^{29, 30}. Cy5- HA cryogels were injected in gp91^phox- mice and B6 mice and degradation was quantified using IVIS (FIG.18F). Cy5-HA cryogels did not degrade appreciably in the gp91^phox- over the course of the two-month study whereas the Cy5-HA cryogels in B6 mice degraded within 4 weeks, as expected (FIG.18G). Taken together, these results suggest that inducing immune deficiency by depletion affects cell infiltration in Cy5-HA cryogels but does not affect degradation. However, deficiencies which functionally impair neutrophils, modeled by NSG and gp91^phox- mice are sufficient to significantly affect Cy5-HA cryogel degradation. C. HA cryogels are neutrophil responsive in post-HSCT mice Next, Cy5-HA cryogel degradation in post-HSCT mice was quantified. B6 recipients were irradiated 48 hours prior to i.v. injection of lineage depleted hematopoietic stem cells (1 x 10⁵ cells, ~87.5% depleted) isolated from bone marrow of syngeneic B6 donor mice (FIG. 21A). Concurrently, B6 recipients and control mice (B6, non-irradiated that do not receive a transplant) were injected subcutaneously with Cy5-HA cryogels, and the degradation rate was compared (FIG.22A). In contrast to non-irradiated mice, a steady fluorescence signal was quantified for about 20 days in post-HSCT mice after which it decreased, corresponding to HA cryogel degradation, at a rate comparable to that in non-irradiated mice. The time interval to 50% of the initial fluorescence intensity was approximately 30 days in post-HSCT mice whereas in non-irradiated mice, a comparable decrease was achieved by day 13 (FIG.22B, FIG.21B). To quantify infiltrating myeloid subsets, Cy5-HA cryogels were excised on days 5 and 16 post-injection in non-irradiated mice and excised on days 5, 16, 21, and 26 in post- HSCT mice (FIG.22C). Viability of infiltrating cells, quantified by negative AnnexinV staining, was initially lower 5- and 16-days post-injection, and increased by day 21 (FIG. 21C). In non-irradiated B6 mice, the number of infiltrating myeloid cells decreased by 96% from days 5 to 16 post-injection (FIG.22D), mirroring near-complete Cy5-HA cryogel degradation (FIG.22B, FIG.21B). In contrast, myeloid cell infiltration in Cy5-HA cryogels was significantly delayed and 97% lower than that of the non-irradiated group, 5 days post- injection. In post-HSCT mice, appreciable myeloid infiltration was not quantified until about day 21 post-HSCT, which was still 67% lower when compared with HA cryogels from non- irradiated mice on day 5 (FIG.22D). Macrophage infiltration in Cy5-HA cryogels in non-irradiated mice decreased 87% from days 5 to 16 (FIG.22E). On day 5 in post-HSCT mice, macrophage infiltration in Cy5- HA cryogels was reduced by about 92% compared to non-irradiated mice. By day 26, infiltrating macrophages in some post-HSCT mice were quantified but remained significantly lower than macrophage infiltration on day 5 in non-irradiated mice (FIG.22E). Neutrophils constituted a majority of the myeloid cells in Cy5-HA cryogels in non- irradiated mice on day 5, but not by day 16 (FIG.22F) when the majority of myeloid cells were macrophages (FIG.21D). In contrast, very few cells were in HA cryogels retrieved on day 5 in post-HSCT mice with a near absence of neutrophils, in contrast with non-irradiated mice at the same timepoint. Neutrophil infiltration in Cy5-HA cryogels was quantified 21 days post-injection but was still 62% lower than on day 5 in non-irradiated mice (FIG.22F). In post-HSCT mice, macrophages constituted most of the cell infiltrates 5- and 16-days after injection, whereas a majority of myeloid cells were neutrophils on days 21 and 26 (FIG. 21D). This data supports that irradiation reduces myeloid infiltration in Cy5-HA cryogels, delays cryogel degradation, and degradation coincides with neutrophil recovery. To assess whether the uniqueness of the results could be attributed to the HA cryogels, the results were compared with hydrolytically degradable oxidized alginate (OxAlg), also functionalized with Tz and Nb (FIG.21E). Unlike HA, OxAlg is not a substrate for endogenous enzymes ^{31, 32}. Tz-functionalized OxAlg was functionalized with Cy5 and Cy5-OxAlg cryogels were formed in the same manner as high-DOS Cy5-HA cryogels. In vitro, Cy5-OxAlg cryogels fully degraded in 1x PBS over 9-days (FIG.21F). In contrast to Cy5-HA cryogels, Cy5-OxAlg cryogels injected in B6 and post-HSCT B6 mice degraded rapidly at a comparable rate, with approximately 70% reduction in fluorescence signal within 24 hours post-injection (FIG.21G).

D. HA cryogels sustain G-CSF delivery and enhance post-HSCT reconstitution of neutrophils The delay in post-HSCT degradation of HA cryogels was leveraged to mediate G- CSF release and enhance neutrophil recovery.1μg of Cy5-labeled G-CSF (Cy5 G-CSF) was encapsulated in HA cryogels and one cryogel was injected either in 1-day post-HSCT or in non-irradiated B6 mice. Encapsulated Cy5 G-CSF was quantified using IVIS and normalized to the initial 8-hour timepoint fluorescence signal (FIG.23A). Cy5 G-CSF release, assessed by fluorescence attenuation, from non-irradiated mice proceeded in a sustained manner immediately post-injection with over 80% released after approximately 12-days post- injection. In post-HSCT mice, 20% Cy5 G-CSF released after approximately 12-days post- injection and subsequently released in a sustained manner (FIG.23B). The time to 50% fluorescence intensity in non-irradiated mice was 5.9 ± 3.0 days compared to 15.5 ± 5.9 days in post-HSCT mice (FIG.24). Then, the effect of G-CSF delivery on peripheral blood neutrophil recovery and acceleration of Cy5-HA cryogel degradation was assessed. Mice receiving either two blank Cy5-HA cryogels or two G-CSF-encapsulated HA-cryogels were compared and, as a positive control, mice with blank Cy5-HA cryogels injected systemically with 2μg pegylated (PEG) G-CSF (FIG.23C) were included, corresponding to the clinical- equivalent dose for mice ^{33, 34}. Mice were bled at pre-determined timepoints, and peripheral blood neutrophil concentration, quantified by flow cytometry, was consistently higher when G-CSF from Cy5-HA cryogels was delivered, and comparable with PEG G-CSF treatment than in mice which received blank Cy5-HA cryogels (FIG.23D). Moreover, Cy5-HA cryogel degradation was accelerated with G-CSF or PEG G-CSF treatment (FIG.23E). These results support that G-CSF release from HA cryogels can improve neutrophil recovery in lethally radiated mice and Cy5-HA cryogel degradation may simultaneously be used as an indicator of functional neutrophil recovery. Summary This example demonstrates an immune responsive biodegradable HA cryogel scaffold that provides sustained G-CSF release and accelerates post-HSCT neutrophil recovery in mice which, in turn, accelerates HA cryogel degradation in vivo. Harnessing post-HSCT immune deficiency to sustain G-CSF release is distinct conceptually from other methods of drug delivery. It is well established that immune cells sense implanted materials as non-self and mount a well-characterized sequential response to isolate the implant in a fibrous capsule ^35-37. In this work, neutrophil infiltration was observed during the acute stages of inflammation and were shown to be key mediators in HA cryogel degradation. This finding is consistent with prior reports that have supported neutrophils as key mediators of shaping the early implant microenvironment and for in vivo destruction of implanted polymeric materials by neutrophil-derived oxidants ^38-40. The finding of primarily myeloid-lineage immune cell populations within the HA cryogel is consistent with previous observations of cell infiltration occurring within scaffolds of a similar composition ^{41, 42}. The encapsulation and release of G- CSF from the polymer scaffold was demonstrated to mediate recovery of neutrophils in the peripheral blood, significantly faster than control mice receiving blank HA cryogels and comparable to pegylated GCSF, which accelerated HA cryogel degradation. HA was selected as the primary constituent polymer as it is ubiquitous in the extracellular matrix and has a long history of clinical use as a biodegradable material in a range of biomedical applications ^43-48. In this work, commercially purchased HA was derivatized with bioorthogonal Tz and Nb groups to facilitate crosslinking without the need for external energy input or addition of external agents such as stabilizers and catalysts ^{49, 50}, which can make it challenging to purify the final product. The use of HA-Tz and HA-Nb also facilitated cryogelation at a slower rate, compared to free-radical polymerization methods, and consequently provided enhanced control over the crosslinking process ^{51, 52}. Moreover, other common cross-linking strategies that directly target the carboxylic acid or hydroxyl side chains groups and unreacted agents may inadvertently react with encapsulated proteins ^53-56. Further, Tz can be quantified spectroscopically and the DOS was readily assessed ^{57, 58}. Consistent with prior work, these results show that DOS affected the rate of HA cryogel degradation by enzymatic cleavage ^{22, 62}. On the other hand, the paradoxical observation that DOS did not affect in vivo degradation is also consistent with prior work that has demonstrated that partial degradation of HA by non-enzymatic means in vivo overcomes steric factors which might otherwise hinder enzymatic access to HA and, in prior works, facilitated equalization of the in vivo degradation rate of low- and high- DOS HA cryogels ⁵⁹. OThese results indicate that activated neutrophils mediate degradation of HA cryogels in vivo, consistent with past reports of the role of reactive oxygen species from activated neutrophils in mediating HA degradation ^60-63 and of neutrophils in the acute phase of the foreign body response ^{35, 36}, which further clarifies how immune deficiency impacts the rate of degradation ^{9, 64}. These results also indicate that while despite successfully depleting neutrophils in the peripheral blood, antibody-based depletion did not achieve a similar depletion of infiltrating neutrophils in HA cryogels and degradation was unaffected in B6 mice. In NSG mice, which have defective adaptive and innate immune cells, Cy5-HA cryogels degraded minimally over 3 months and neutrophil infiltration into the HA cryogel was not sustained. The observation is consistent with the well-documented lack of adaptive immune cells, impaired innate immune cell subsets (e.g. macrophages) and a lack of a functional complement system which affects the activation of neutrophils in these mice ^65-68. These results were expanded upon by quantifying Cy5-HA cryogel degradation in gp91^phox- mice, which are on the B6 background, but gp91^phox- neutrophils in affected hemizygous male mice lack superoxide production. The functional deficiency of neutrophils in gp91^phox- is similar to the clinical observations of defective respiratory burst and phagocytosis affecting neutrophils in chronic granulomatous disease, in which there are normal neutrophil counts but impaired oxidative killing ²⁹. In these mice, the absence of appreciable degradation of Cy5-HA cryogels provides additional support for the key role of functional neutrophils in facilitating degradation. The key role of functional neutrophils in HA cryogel degradation was further validated in post-HSCT mice, modeling transient innate immune deficiency. Unlike antibody- based depletion, irradiating mice achieves elimination of all immune cells and neutrophils predominate the earliest immune cells that reconstitute post-HSCT ⁶⁹. Similar to gp91^phox- mice, post-HSCT respiratory burst and phagocytosis of neutrophils are generally decreased in humans for up to 3 months, underscoring the importance of qualitatively assessing functionality of neutrophils ⁷⁰. These results indicate that Cy5-HA cryogel degradation was delayed until neutrophil infiltration into Cy5-HA cryogels recovered, further supporting the role of neutrophils in mediating HA degradation and the immune responsive behavior of HA cryogels. These results are consistent with past reports in which rapid neutrophil infiltration and activation have been identified as one of the earliest cellular events of the foreign body response ^{2, 71}. In contrast, it was shown that OxAlg cryogels, which have hydrolytically labile groups but are not a substrate for endogenous enzymes, degrade rapidly in vivo at similar rates in immune competent and post-HSCT mice ^{31, 32, 72}. These observations characterizing the importance of neutrophils in HA cryogel degradation support the unique immune responsiveness of HA cryogels. Similar to PEG-G-CSF, it was demonstrated that the effect of G-CSF release from HA cryogels is neutrophil-dependent ⁷³, and therefore might be characterized as self-regulating. However, in contrast to PEG-G-CSF, G-CSF delivery from HA cryogels avoids the potential of pre-existing or induced anti-PEG antibody (APA)-mediated rapid clearance ^{74, 75}. In immune competent mice, it has been demonstrated that the administration of PEG-G-CSF at a clinically-relevant single dose elicits anti-PEG IgM antibodies in a dose-dependent manner which subsequently accelerates clearance of a second PEG-G-CSF dose via an anti-PEG IgM-mediated complement activation ²¹. De novo anti-PEG antibody induction may not require T cell activation ⁷⁶and therefore could also be induced in post-HSCT immunodeficient hosts. PEG G-CSF may therefore be less effective with pre-existing or induced APA ⁷⁷. Therapy-induced neutropenia substantially limits the applicability of therapies that could be life-saving. HA cryogels not only deliver G-CSF in a sustained manner to enhance neutrophil regeneration, while avoiding the potential of APA-mediated enhanced clearance, but also show a responsive degradation behavior. Collectively, these findings support that the HA cryogels might be leveraged to enhance and functionally assess neutrophil functionality and aid in treatment-related decisions for recipients of myelosuppressive therapy. Materials and Methods The following Materials and Methods were used in Example 2. General methods and statistics Sample sizes for animal studies were based on prior work without use of additional statistical estimations. Results were analyzed where indicated using student’s t-test and two- way ANOVA with Bonferroni’s test using Graphpad Prism software. Mixed-model linear regression was conducted using IBM SPSS statistical package. Alphanumeric coding was used in blinding for pathology samples and cell counting. Chemicals Sodium hyaluronate (MW 1.5-2.2 MDa, Pharma Grade 150, lot: 18011K) and sodium alginate (MW ~250 kDa, Pronova UP MVG) were purchased from NovaMatrix. (2- morpholinoethanesulfonic acid (MES), sodium chloride (NaCl), sodium hydroxide (NaOH), N-hydroxysuccinimide (NHS), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC), sodium periodate (311448) and ammonia borane (AB) complex (682098) were purchased from Sigma-Aldrich. (4-(1,2,4,5-tetrzain-3-yl)phenyl)methanamine (tetrazine amine) was purchased from Kerafast (FCC659, lot: 2014).1-bicyclo[2.2.1]hept-5- en-2-ylmethanamine (norbornene amine) was purchased from Matrix Scientific (# 038023, lot: M15S). Cy5-tetrazine amine was purchased from Lumiprobe (lot: 9D2FH).1kDa molecular weight cutoff (MWCO) mPES membrane was purchased from Spectrum (S02- E001-05-N). Derivatization of HA Tetrazine functionalized HA (HA-Tz) or norbornene functionalized HA (HA-Nb) were prepared by reacting tetrazine amine or norbornene amine to HA using EDC/NHS carbodiimide chemistry. Sodium hyaluronate was dissolved in a buffer solution (0.75% wt/vol, pH ~ 6.5) of 100mM MES buffer. NHS and EDC were added to the mixture to activate the carboxylic acid groups on the HA backbone followed by either tetrazine amine or norbornene amine. HA was assumed to be 1.8 MDa for purposes of conjugation reactions. To synthesize 7% DOS HA-Tz (high-DOS), the molar ratios of HA:EDC:NHS:tetrazine are 1:25000:25000:2500. To synthesize 0.8% DOS HA-Tz (low-DOS), the molar ratios of HA:EDC:NHS:tetrazine are 1:2860:2860:286. To synthesize HA-Nb, the molar ratios of HA:EDC:NHS:norbornene are 1:25000:25000:2500. Each reaction was stirred at room temperature for 24 hours and transferred to a 12,000Da MW cutoff dialysis sack (Sigma Aldrich) and dialyzed in 4L of NaCl solutions of decreasing molarity (0.125M, 0.100M, 0.075M, 0.050M, 0.025M, 0M, 0M, 0M, 0M) for 8 hours per solution. After dialysis, solutions containing HA-Tz or HA-Nb were frozen overnight and lyophilized (Labconco Freezone 4.5) for 48 hours. Cy5 conjugated HA-Nb (Cy5-HA-Nb) was synthesized following a previously described technique with some modifications ⁷⁸.0.8mg of Cy5-Tz was reacted with 100mg of HA-Nb at 0.2 wt/vol in DI water for 24 hours at 37 ºC and purified by dialysis in DI water using a 12,000Da MW cutoff dialysis sack for 48 hours. Dialysis water bath was changed once every 8 hours. Cy5-HA-Nb was then frozen overnight and lyophilized for 48 hours. Preparation of oxidized alginate Alginate was oxidized by mixing a 1% wt/vol solution of sodium alginate in DI water with an aqueous solution of 23 mM sodium periodate (Sigma Aldrich) to achieve a 1:586 molar ratio of alginate: periodate. The reaction was stirred in the dark at room temperature overnight. Sodium chloride (1.8 grams/gram of alginate) was added to solution to achieve a 0.3 M solution, followed by purification via tangential flow filtration (TFF) using a mPES 1kDa molecular weight cutoff (MWCO) membrane (Spectrum) and sequential solvent exchanges with 0.15 M – 0.10 M – 0.05 M and 0.0 M sodium chloride in DI water. The resulting solution was treated with ammonia borane (AB) complex (Sigma Aldrich) at 1:4 alginate:AB molar ratio and stirred at room temperature overnight. Sodium chloride (1.8 grams/gram of alginate) was added to solution to achieve a 0.3 M solution, followed by purification via TFF using a 1kDa MWCO mPES membrane and sequential solvent exchanges with 0.15 M – 0.10 M – 0.05 M and 0.0 M sodium chloride in DI water. The resulting solution was lyophilized to dryness. Derivatization of oxidized alginate To synthesize tetrazine and norbornene functionalized oxidized alginate (OxAlg-Tz, OxAlg-Nb respectively), oxidized alginate, prepared as described above, was solubilized in 0.1 M MES buffer,0.3 M sodium chloride, pH 6.5 at 1%wt/vol. NHS and EDC were added to the mixture followed by either tetrazine or norbornene. The molar ratio of oxidized alginate:NHS:EDC:tetrazine or norbornene was 1:5000:5000:1000. The reaction was stirred in the dark at room temperature overnight. The resulting solution was centrifuged at 4700 rpm for 15 minutes and filtered through a 0.2-micron filter. The solution was purified via TFF using a mPES 1kDa molecular weight cutoff (MWCO) membrane and sequential solvent exchanges with 0.15 M – 0.10 M – 0.05 M and 0.0 M sodium chloride in DI water. The purified solution was treated with activated charcoal (1 gram / gram of alginate) for 20 minutes at room temperature. The slurry was filtered through 0.2-micron filter and the filtrate was lyophilized to dryness. Endotoxin Testing Endotoxin testing of high-DOS HA-Tz and Cy5-HA-Nb were conducted using a commercially available endotoxin testing kit (88282, Thermo Fisher Scientific, lot: VH310729) and following manufacturer’s instructions. High-DOS HA-Tz and Cy5-HA-Nb were solubilized at 0.6 wt% in endotoxin free water and samples were tested in technical triplicates. To calculate endotoxin content of a single HA cryogel, the EU/mL concentration for high-DOS HA-Tz and Cy5-HA-Nb were divided by 2 (relative concentrations of HA-Tz and HA-Nb in HA cryogels are 0.3 wt%) and multiplied by 0.03 (30uL of volume per HA cryogel). EU/kg was calculated based on 2 HA cryogels administered into a mouse with an average weight of 20 grams. Cryogel development This study followed a previously described cryogelation method^78-80. To form cryogels, aqueous solutions of 0.6% wt/vol HA-Tz and HA-Nb or OxAlg- Tz and OxAlg-Nb were prepared by dissolving lyophilized polymers into deionized water and left on a rocker at room temperature for a minimum of 8 hours to allow for dissolution. The aqueous solutions were then pre-cooled to 4ºC before cross-linking to slow reaction kinetics. HA-Tz and HA- Nb or OxAlg- Tz and OxAlg-Nb solutions were mixed at a 1:1 volume ratio, pipetted into 30μL Teflon molds which were pre-cooled to -20 ºC, and quickly transferred to a -20 ºC freezer to allow for overnight cryogelation. Synthesis of Cy5-HA or Cy5-OxAlg cryogels followed the same protocol as above, substituting Cy5-HA-Nb for HA-Nb or Cy5-OxAlg-Nb for OxAlg-Nb. Pore size analysis of HA cryogels For scanning electron microscopy (SEM), frozen HA cryogels were lyophilized for 24 hours and in a petri dish. Lyophilized HA cryogels were adhered onto sample stubs using carbon tape and coated with iridium in a sputter coater. Samples were imaged using secondary electron detection on a FEI Quanta 250 field emission SEM in the Nano3 user facility at UC San Diego. Fluorescence images of Cy5-HA cryogels were acquired using a Leica SP8 All experiments were performed at the UC San Diego School of Medicine Microscopy Core. Pore size quantification of SEM images and relative distribution of pore sizes of confocal images was done using FIJI image processing package ⁸¹. HA cryogel pore-interconnectedness analysis Cy5-HA cryogels were synthesized with low- and high-DOS HA-Tz and incubated in 1mL of FITC-labeled 10µM diameter melamine resin micro particles (Sigma Aldrich) at 0.29mg/mL concentration on a rocker at room temperature overnight. Fluorescence images of Cy5-HA cryogels with FITC-labeled microparticles were acquired using a Leica SP8 confocal. Interconnectedness of the HA cryogels was determined by generating 3D renderings of confocal z-stacks using FIJI imaging processing package and assessing fluorescence intensity of both the Cy5 and FITC channels with depth starting from the top of the HA cryogel. To determine the effect of injection on pore interconnectedness, HA cryogels were injected through a 16G needle prior to incubation in FITC-labeled microparticle solution. All experiments were performed at the UC San Diego School of Medicine Microscopy Core. In vitro degradation of Cy5-HA cryogels Cy5-HA cryogels synthesized with low- and high-DOS HA-Tz and placed into individual 1.5mL microcentrifuge tubes (Thermo Scientific) with 1mL of 100U/mL Hyaluronidase from sheep testes Type II (HYAL2, H2126, Sigma Aldrich, lot: SLBZ9984) in 1x PBS. Degradation studies were conducted in tissue culture incubators at 37 ºC. Supernatant from samples were collected every 24 – 72 hours by centrifuging the samples at room temperature at 2,000G for 5 minutes and removing 0.9mL of supernatant. Cy5-HA cryogels were resuspended by adding 0.9mL of freshly made 100U/mL HYAL2 in 1x PBS. Fluorescence measurements were conducted using a Nanodrop 2000 Spectrophotometer (Thermo Fisher Scientific) and these values were normalized to sum of the fluorescence values over the course of the experiment. All experiments were performed at UC San Diego. In vitro degradation of Cy5-OxAlg Cryogels Cy5-OxAlg cryogels were placed into individual 1.5mL microcentrifuge tube with 1mL of 1x PBS. Degradation studies were conducted in tissue culture incubators at 37ºC. Supernatant from samples were collected every 24 – 72 hours by removing visible Cy5- OxAlg cryogel material with tweezers and transferring to new 1.5mL microcentrifuge tube with 1mL of 1x PBS. Fluorescence measurements were conducted using a Nanodrop 2000 Spectrophotometer and these values were normalized to sum of the fluorescence values over the course of the experiment. All experiments were performed at UC San Diego. In vivo mouse experiments All animal work was conducted at the Moores Cancer Center vivarium at UC San Diego, except NSG mouse IVIS imaging experiments, which were conducted at the Harvard Biological Research Infrastructure vivarium at Harvard University and approved by the respective Institutional Animal Care and Use Committee (IACUC). All animal experiments followed the National Institutes of Health guidelines and relevant AALAC-approved procedures. Female C57BL/6J (B6, Jax # 000664) and NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG, Jax # 005557) mice were 6-8 weeks at the start of the experiments. Male B6.129S- Cybb^tm1Din (gp91^phox-, Jax # 002365) mice were 6-8 weeks old at the start of experiments. All mice in each experiment were age matched and no randomization was performed. The pre- established criteria for animal omission were failure to inject the desired cell dose in transplanted mice and death due to transplant failure. Health concerns unrelated to the study (e.g. malocclusion) and known mouse-strain specific conditions that affected measurements (e.g. severe dermatitis and skin hyperpigmentation in B6 mice) were criteria for omission. Immune depletion in mice Neutrophil depletion in B6 mice was achieved by following the previously established protocol ^{28, 82}. Briefly, 25μL of anti-mouse Ly6G antibody (1A8, Bio X Cell, lot: 737719A2)) was administered i.p. every day for the first week. Concurrently, 50μL of anti-rat κ immunoglobulin light chain antibody (MAR 18.5, Bio X Cell, lot: 752020J2) was administered every other day starting on the second day of depletion. After one week, the dose of the anti-mouse Ly6G antibody was increased to 50μL. Macrophage depletion in B6 mice was induced by i.p. administration of 100uL of clodronate liposomes (Liposoma, lot: C44J0920) every 3-days. B cell lineage depletion in B6 mice was induced by i.p. administration of 400μg of anti-mouse B220/CD45R antibody (RA3.31/6.1, Bio X Cell, lot: 754420N1) once every 3-days. T cell lineage depletion in B6 mice was induced by i.p. administration of 400μg dose of anti-mouse CD4 antibody (GK1.5, Bio X Cell, lot: 728319M2) and 400μg dose of anti-mouse CD8α antibody (2.43, Bio X Cell, lot:732020F1) once every 3-days. For all lineage depletion models, mice received intraperitoneal injections of 0.1mL (400μg) of antibodies or 0.1mL of clodronate liposome solution 3 days before subcutaneous HA cryogel or Cy5-HA cryogel injection. Depletion started 3-days prior to Cy5-HA cryogel administration to mice and continued until complete cryogel degradation or until mice were euthanized and cryogels retrieved for analysis. All experiments were performed at the Moores Cancer Center vivarium at UC San Diego. FIG.25 further provides a table in which the methods and durability of immune cell depletion are described. Transplant models Irradiations were performed with a Cesium-137 gamma-radiation source irradiator (J.L. Shepherd & Co.). Syngeneic HSCT (B6 recipients) consisted of 1 dose of 1,000 cGy + 1 x 10⁵ lineage-depleted bone marrow cells from syngeneic B6 donors. Bone marrow cells for transplantation (from donors) or analysis were harvested by crushing all limbs with a mortar and pestle, diluted in 1x PBS, filtering the tissue homogenate through a 70 μm mesh and preparing a single-cell suspension by passing the cells in the flowthrough once through a 20- gauge needle. Total cellularity was determined by counting cells using a hemacytometer. Bone marrow cells were depleted of immune cells (expressing CD3ε, CD45R/B220, Ter-119, CD11b, or Gr-1) by magnetic selection using a Mouse Hematopoietic Progenitor Cell Enrichment Set (BD Biosciences # 558451, lot: 0114777). To confirm depletion, cells were incubated with a mix of Pacific Blue-conjugated lineage specific antibodies (antibodies to CD3, NK1.1, Gr-1, CD11b, CD19, CD4 and CD8) and with Sca-1 and cKit-specific antibodies for surface staining and quantification of Lineage- fraction of cells, which were > 87% lineage depleted. Subsequently, cells were suspended in 100μL of sterile 1x PBS and administered to anesthetized mice via a single retroorbital injection. All experiments were performed at the Moores Cancer Animal Facility at UC San Diego Health. All flow cytometry experiments were performed using an Attune^® NxT Acoustic Focusing cytometer analyzer (A24858) at UC San Diego. Subcutaneous cryogel administration While mice were anesthetized, a subset received a subcutaneous injection of HA cryogel or OxAlg cryogel, which was suspended in 200μL of sterile 1x PBS, into the dorsal flank by means of a 16G needle positioned approximately midway between the hind- and forelimbs. The site of injection was shaved and wiped with a sterile alcohol pad prior to gel injection. In vivo degradation In vivo Cy5-HA cryogel degradation was performed with Cy5-HA cryogels synthesized with low- and high-DOS Tz-HA in untreated B6 mice, immune deficient B6 mice, NSG mice, and gp91^phox- mice. In vivo Cy5 OxAlg cryogel degradation was performed in non-irradiated, non-transplanted B6 mice and B6 mice post-HSCT. In all cases, cryogels were administered into the dorsal flank of an anesthetized mouse and the fluorescent intensity of the Cy5-HA cryogel was quantified using an IVIS spectrometer (PerkinElmer) at predetermined timepoints and analyzed using LivingImage software (PerkinElmer). At each timepoint, mice were anesthetized and the area around the subcutaneous cryogel was shaved to reduce fluorescence signal attenuation. Fluorescence radiant efficiency, the ratio of fluorescence emission to excitation, was measured longitudinally as a metric to quantify fluorescence from subcutaneous cryogels. These values were normalized to the measured signal on day 3. All experiments were performed at the Moores Cancer Microscopy Core Facility at UC San Diego Health, with the exception of NSG mouse in vivo degradation experiments, which were performed at the Harvard Biology Research Infrastructure vivarium using an IVIS spectrometer (PerkinElmer). Flow cytometry analysis Anti-mouse antibodies to CD45 (30-F11, lot: B280746), CD11b (M1/70, lot: B322056), CD4 (RM4-5, lot: B240051), CD8α (53-6.7, lot: B266721), B220 (RA3-6B2, lot: B298555), Ly6-G/Gr-1 (1A8, lot: B259670), lineage cocktail (17A2/RB6-8C5/RA3-6B2/Ter- 119/M1/70, lot: B266946), Ly-6A/E/Sca-1 (D7, lot: B249343), and CD117/cKit (2B8, lot: B272462) were purchased from Biolegend. Anti-mouse F4/80 (BM8, lot: 2229150) and was purchased from eBioscience. All cells were gated based on forward and side scatter characteristics to limit debris, including dead cells. AnnexinV (Biolegend, lot: B300974) stain was used to separate live and dead cells. Antibodies were diluted according to the manufacturer’s suggestions. Cells were gated based on fluorescence-minus-one controls, and the frequencies of cells staining positive for each marker were recorded. To quantify T cells, B cells, monocytes, and neutrophils in peripheral blood, blood was first collected from the tail vein of mice into EDTA coated tubes (BD). Samples then underwent lysis of red blood cells and were stained with appropriate antibodies corresponding to cell populations of interest. To quantify infiltrating immune cells within Cy5-HA cryogels, mice were sacrificed, cryogels removed, and HA cryogels crushed against a 70-micron filter screen before antibody staining. Absolute numbers of cells were calculated using flow cytometry frequency. Flow cytometry was analyzed using FlowJo (BD) software. All flow cytometry experiments were performed using a Attune^® NxT Acoustic Focusing cytometer analyzer (A24858) at UC San Diego. Histology After euthanasia, HA cryogels were explanted and fixed in 4% paraformaldehyde (PFA) for 24 hours. The fixed HA cryogels were then transferred to 70% ethanol solution. Samples were routinely processed and sections (5μm) were stained and digitized using an Aperio AT2 Automated Digital Whole Slide Scanner by the Tissue Technology Shared Resource at the Moores Cancer Center at UC San Diego Health. Digital slides were rendered in QuPath and positive cell detection was used to quantify the total number of mononuclear cells within each image. Quantification of mononuclear cell density was determined for each histological section. Immunohistochemistry (IHC) Paraffin embedded HA cryogel sections were baked at 60 ºC for 1 hr. Tissues were then rehydrated through successive washes (3x xylene, 2x 100% ethanol, 2x 95% ethanol, 2x 70% ethanol, di-water). After rehydration, antigen retrieval was conducted using Unmasking solution (Citrate based, pH 6) (Vector Laboratories, H-3300) at 95 ºC for 30 minutes. Staining was performed using Intellipath Automated IHC Stainer (Biocare). A peroxidase block, Bloxall (Vector Laboratories, SP-6000) was performed for 10 minutes, followed by 2x washes in 1x tris-buffered saline with 0.1% Tween 20 (TBST, Sigma Aldrich), and a blocking step using 3% Donkey Serum for 10 minutes. Samples were stained using anti- Ly6G primary antibody (Rabbit, Cell Signaling Technology, 87048S) at 1:100 concentration for 1 hr. Samples were washed twice in TBST and anti-rabbit HRP polymer (Cell IDX, 2HR- 100) was added for 30 minutes. Samples were washed twice in TBST and DAB (brown) Chromogen (VWR, 95041-478) was added for 5 minutes. This was followed by 2x washes in di-water, 5-minute incubation with Mayer’s Hematoxylin (Sigma, 51275), 2x washes in TBST, and 1x wash in di-water. Mounting was performed using a xylene-based mountant. IHC was performed by the Tissue Technology Shared Resource at the Moores Cancer Center at UC San Diego Health. G-CSF encapsulation To quantify G-CSF release from HA cryogels, recombinant human G-CSF (300-23, Peprotech, lots: 041777 and 041877) was reacted with sulfo-Cy5 NHS ester (13320, Lumiprobe, lot 7FM7C) at a 1:25 molar ratio of G-CSF:sulfo-Cy5 NHS ester in MES buffer to form Cy5 G-CSF. Unreacted sulfo-Cy5 NHS ester was removed by overnight dialysis on a 10kDa dialysis membrane.1μg of Cy5 G-CSF was added to 0.6% wt/vol HA-Tz solution before mixing with HA-Nb and cryogelation as described above. To track Cy5-HA cryogel degradation in mice which received G-CSF loaded Cy5-HA cryogels, the same protocol is followed substituting G-CSF for Cy5 G-CSF and Cy5-HA-Nb for HA-Nb. Neutrophil reconstitution models Mice were irradiated and administered an autologous HSCT as described above. PEG G-CSF (MBS355608, MyBioSource, lot: R15/2020J) or G-CSF was injected i.p. Cy5-HA cryogel encapsulating G-CSF was injected subcutaneously as described above, 24 hours post- HSCT. Mice were bled at predetermined timepoints and relevant immune subsets were stained for flow cytometry. Calculations The second order rate constant (k) for Tz-Nb reaction has been previously estimated to be 1.3 - 1.7 M^-1s^-1 at 21ºC (room temperature).^1,2 In this system, for high-DOS Tz-HA and Nb-HA the concentration is 0.55mM at the start of the reaction. The reaction rate can be calculated as:

The rate of reaction was calculated to be about 40µM/s from equation 1 and the time to completion to be about 46.3 minutes at 21ºC. In this system, the initial temperature is 4ºC and therefore the actual time for completion of the reaction would be significantly longer. As the solution cools and freezes during the crosslinking process, the freezing time was estimated. First, the energy required to freeze 30uL of HA solution starting from 4ºC and ending at 0ºC was determined using:

The energy required to freeze 30µL HA solution from 4ºC to 0ºC is 10.5J³. Since the HA solution is very dilute (0.6 wt%), the enthalpy of formation and density was approximated to that of water. To calculate the freezing time, the rate of energy extraction from the HA solution was estimated. Since the teflon cryomold is pre-cooled to -20ºC and rests on a metal shelf in the freezer, the rate of freezing was estimated using the thermal conductivity of teflon, thickness of teflon (25mm), and conductive heat transfer area (5.75mm) using equation 3. To simplify the analysis, it was assumed that convective heat loss at air-cryogel interface is negligible.

The rate of heat transfer is calculated to be 0.010J/s and therefore the time to reach 0ºC is ~16.8 minutes. Since conductive heat loss through the edge of the cryogels and convective heat loss through the top was ignored, the calculated time represents an overestimation for the freezing time but is still significantly below that of the time to reaction completion. It was also experimentally verified that a 30uL drop of Tz-HA/Nb-HA solution freezes in about 10 minutes. Calculation References: 1. Vrabel M, Kölle P, Brunner KM, Gattner MJ, López-Carrillo V, de Vivie-Riedle R, Carell T. Norbornenes in inverse electron-demand Diels-Alder reactions. Chemistry. 2013;19(40):13309-12. 2. Devaraj, N. K., Weissleder, R., & Hilderbrand, S. A. (2008). Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjugate chemistry, 19(12), 2297–2299. https://doi.org/10.1021/bc8004446 3. https://www.engineeringtoolbox.com/saturated-ice-steam-d_970.html

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Nature Methods 9, 676-682 (2012). 82. Stackowicz, J., Jönsson, F. & Reber, L.L. Mouse models and tools for the in vivo study of neutrophils. Frontiers in immunology 10, 3130 (2020). INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control. EQUIVALENTS Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the present invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

CLAIMS What is claimed is: 1. A method of delivering an active agent to a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, the method comprising: administering to the subject a scaffold composition comprising hyaluronic acid and an active agent, thereby delivering the active agent to the subject.

2. A method of modulating the activity of an innate leukocyte, restoring levels of functional innate leukocytes, reconstituting the levels of functional innate leukocytes and/or enhancing the regeneration of functional innate leukocytes in a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, the method comprising: administering to the subject a scaffold composition comprising hyaluronic acid and an active agent, thereby modulating the activity of an innate leukocyte, reconstituting the levels of innate leukocyte and/or enhancing the regeneration of an innate leukocyte in the subject.

3. The method of claim 1 or 2, wherein the active agent (i) modulates the activity of an innate leukocyte; (ii) restores levels of functional innate leukocytes; (iii) reconstitutes levels of functional innate leukocytes; (iv) enhances the regeneration of functional innate leukocytes in the subject; (v) enhances immunity of the subject in need thereof; and/or (vi) treats or prevents a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes.

4. A method for detecting immune recovery in a subject having a deficiency in levels of functional innate leukocytes, comprising: administering to the subject a scaffold composition comprising hyaluronic acid, assessing the level of degradation of the scaffold composition, wherein degradation of the scaffold composition is indicative of immune recovery in the subject.

5. The method of claim 5, wherein the scaffold composition further comprises an active agent.

6. The method of any one of claims 1-6, wherein the method provides for controlled, sustained, and/or delayed release of the active agent upon administration to the subject.

7. The method of any one of claim 4-6, wherein degradation of the scaffold composition is indicative of (i) modulation of the activity of an innate leukocyte; (ii) restoration of levels of functional innate leukocytes; (iii) reconstitution of levels of functional innate leukocytes; (iv) regeneration of functional innate leukocytes in the subject; (v) enhanced immunity of the subject; and/or (vii) treatment or prevention of a disorder in the subject, wherein the disorder is caused by or associated with a deficiency in functional innate leukocytes.

8. The method of any one of claims 1-7, wherein the scaffold composition degrades upon exposure to functional innate leukocytes.

9. The method of any one of claims 1-8, wherein the innate leukocyte: (i) is selected from the group consisting of a natural killer cell, a mast cell, an eosinophil, a basophil, a macrophage, a dendritic cell, a gamma-delta (γδ) T cell, and a neutrophil; and/or (ii) is not a dendritic cell.

10. The method of any one of claims 1-9, wherein the innate leukocyte comprises a neutrophil.

11. The method of any one of claims 1-3 or 5-10, wherein the active agent: (i) comprises an amino acid, a peptide, a protein, a nucleic acid, an oligonucleotide, a small molecule, or a combination thereof; (ii) comprises a protein, optionally, wherein the protein is an isolated protein and/or a recombinant protein; (iii) comprises a cytokine, a chemokine, and/or a growth factor; (iv) comprises a cytokine, optionally, a pro-inflammatory cytokine and/or an anti- inflammatory cytokine; (v) is selected from the group consisting of a granulocyte colony stimulating factor (G-CSF), a granulocyte-macrophage colony-stimulating factor (GM-CSF), a bone morphogenetic protein 2 (BMP2), a stromal cell-derived factor (SDF), a platelet activating factor (PAF), a tumor necrosis factor α (TNFα), an interleukin-1 (IL-1), an interleukin-1α (IL-1α), an interleukin-1β (IL-1β), an interleukin-2 (IL-2), an interleukin-3 (IL-3), an interleukin-4 (IL-4), an interleukin-5 (IL-5), an interleukin-6 (IL-6), an interleukin-7 (IL-7), an interleukin-8 (IL-8), an interleukin-9 (IL-9), an interleukin-10 (IL-10), an interleukin-11 (IL-11), an interleukin-12 (IL-12), an interleukin-13 (IL-13), an interleukin-14 (IL-14), an interleukin-15 (IL-15), an interleukin-16 (IL-16), an interleukin-17 (IL-17), an interleukin-18 (IL-18), an interleukin-19 (IL-19), an interleukin-20 (IL-20), an interleukin-21 (IL-21), an interleukin-22 (IL-22), an interleukin-23 (IL-23), an interleukin-24 (IL-24), an interleukin-25 (IL-25), an interleukin-26 (IL-26), an interleukin-27 (IL-27), an interleukin-28 (IL-28), an interleukin-29 (IL-29), an interleukin-30 (IL-30), an interleukin-31 (IL-31), an interleukin-32 (IL-32), an interleukin-33 (IL-33), an interleukin-34 (IL-34), an interleukin-35 (IL-35), an interleukin-36 (IL-36), an interleukin-1 receptor antagonist (IL-1Ra), a growth-related gene product-α (GRO-α), a growth-related gene product-β (GRO-β), a macrophage infiltrating protein-1α (MCP-1α), a macrophage infiltrating protein-1β (MCP-1β), a cytokine-induced chemoattractant (CINC), an interferon-α (IFN-α), an interferon-β (IFN-β), an interferon-γ (IFN-γ), a Fas ligand (FasL), a CD30 ligand (CD30L), a vascular endothelial growth factor (VEGF), a hepatocyte frowth factor (HGF), a transforming growth factor alpha (TGF-α), an oncostain (OSM), a neurotrophin, a monocyte chemoattractant protein-1 (MCP-1), a stem cell factor (SCF), a complement 5a (C5a), and an erythropoietin (EPO); (vi) comprises a G-CSF; (vii) comprises a polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF).

12. The method of any one of claims 1-11 wherein the active agent is G-CSF.

13. The method of any one of claims 1-3 or 5-12, wherein the method further comprises administering an additional active agent.

14. The method of claim 13, wherein (i) the additional active agent is encapsulated in the scaffold; (ii) the additional active agent is administered systemically.

15. The method of any one of claims 1-14, wherein the subject is or has undergone therapy that depletes or reduces the innate leukocyte in the subject.

16. The method of claim 15, wherein the therapy is a chemotherapy or a radiotherapy for the treatment of a cancer.

17. The method of any one of claims 1-16, wherein the composition further comprises a detectable agent.

18. The method of claim 17, (i) wherein the detectable agent is attached to the active agent; (ii) wherein the detectable agent is for detecting the scaffold and/or active agent in vivo; and/or (iii) wherein the detectable agent is for assessing the level of degradation of the scaffold composition.

19. The method of claim 17 or 18, wherein the detectable agent (i) is selected from the group consisting of a dye, a fluorophore, a fluorescent compound, a luminescent compound, a chemiluminescent compound, a radioisotope, a paramagnetic metal ion, a nanoparticle, and a quantum dot, or a combination thereof; (ii) comprises a dye; and/or (iii) is detectable by eye, fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), multi-mode imaging, ultrasound imaging (USI), photoacoustic imaging (PAI), and/or optical coherence tomography (OCT).

20. The method of any one of claims 4-19, wherein assessing the level of degradation of the scaffold comprises detecting the level of the detectable agent and comparing to a detectable agent reference level, optionally, wherein the detectable agent reference level is the level of the detectable agent upon administration of the scaffold composition or at an earlier time point after administration of the scaffold composition. 21. The method of any one of claims 4-20, further comprising obtaining a measurement of (i) the level of the detectable agent and/or active agent in the scaffold prior to administration of the scaffold to the subject; (ii) the level of functional innate leukocytes in the subject prior to administration of the scaffold to the subject; (iii) the level of the innate leukocytes in the subject prior to administration of the scaffold to the subject. (iv) the level of the detectable agent and/or active agent in the scaffold after administration of the scaffold to the subject; (v) the level of functional innate leukocytes after administration of the scaffold to the subject; (vi) the level of the innate leukocytes in the subject prior to administration of the scaffold to the subject; (vii) the level of functional innate leukocytes in the subject before the subject receives a therapy that depletes or reduces the level of the innate leukocyte; and/or (viii) the level of functional innate leukocytes in the subject after the subject receives a therapy that depletes or reduces the level of the innate leukocyte. 20. The method of any one of claims 1-19, wherein: (i) the level of functional innate leukocytes is increased by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 99% or more as compared to a reference level; and/or (ii) the level of functional innate leukocytes is increased by at least about 1-fold, about 2-fold, or about 3-fold or more as compared to a reference level.

21. The method of claim 11, wherein the reference level is a standardized level.

22. The method of claim 21, wherein the reference level is the level of functional innate leukocytes prior to administration of the scaffold composition or at an earlier time point after administration of the scaffold composition.

23. The method of any one of claims 1-27, wherein the scaffold composition does not comprise a differentiation factor that induces the differentiation of a hematopoietic stem cell into a T cell progenitor cell.

24. The method of any one of claims 1-23, wherein the scaffold composition degrades upon exposure to an enzyme produced by the innate leukocyte.

25. The method of any one of claims 1-24, wherein the scaffold composition degrades by neutrophil-mediated oxidation.

26. The method of any one of claims 1-25, wherein degradation of the scaffold composition results in and/or enhances the release of the active agent.

27. The method of any one of claims 17-26, wherein the degradation of the scaffold composition results in and/or enhances the release of the detectable agent.

28. The method of any one of claims 1-27, wherein the scaffold is macroporous or wherein the scaffold comprises pores having a diameter of about 50 microns to about 150 microns, about 80 microns to about 180 microns, or about 40 microns to about 90 microns.

29. The method of any one of claims 1-28, wherein the subject is a human.

30. The method of any one of claims 1-29, wherein the composition is administered to the subject via injection, optionally, intravenously, intramuscularly, or subcutaneously.

31. The method of any one of claims 1-30, wherein the subject has a disorder selected from the group consisting of primary neutropenia, acute neutropenia, severe chronic neutropenia (SCN), severe congenital neutropenia (Kostmann's syndrome), severe infantile genetic agranulocytosis, benign neutropenia, cyclic neutropenia, chronic idiopathic neutropenia, secondary neutropenia, syndrome associated neutropenia, and immune-mediated neutropenia, chronic granulomatous disease, Chediak-Higashi syndrome, Griscelli Syndrome-II, Hermansky-Pudlak Syndrome type 2, leukocyte adhesion deficiency, specific granule deficiency, x-linked neutropenia, myeloperoxidase deficiency, and hyper- IgE syndrome.

32. The method of any one of claims 1-60, wherein the subject has a neutropenia, optionally, wherein the neutropenia is caused by or associated with radiation, alcoholism, drugs, allergic disorders, aplastic anemia, autoimmune disease, T-γ lymphoproliferative disease (T-γ LPD), myelodysplasia, myelofibrosis, dysgammaglobulinemia, paroxysmal nocturnal hemoglobinuria, cancer, vitamin B12 deficiency, folate deficiency, viral infection, bacterial infection, spleen disorder, hemodialysis, or transplantation, toxins, bone marrow failure, Schwachman-Diamond syndrome, cartilage-hair hypoplasia, dyskeratosis congenita, glycogen storage disease type IB, splenomegaly of any cause, and intrinsic defects in myeloid cells or their precursors.

33. The method of any one of claims 1-32, wherein the subject has or is receiving a hematopoietic stem cell transplantation (HSCT).

34. The method of claim 33, wherein the administration of the composition is prior to, concurrently with, or subsequent to the HSCT.

35. The method of any one of claims 1-34, wherein the method reconstitutes the innate leukocyte within 7 days, 14 days, 21 days, or 28 days.

36. The method of any one of claims 1-35, wherein the reconstitution of the innate leukocyte results in the level of innate leukocyte to be at least about 75%, 80%, 85%, 90%, 95% or 99% of a reference level.

37. The method of claim 36, wherein the reference level is (i) a standardized level; (ii) the level of the innate leukocyte of the subject before depletion of the level of the innate leukocyte; and/or (iii) the level of the innate leukocyte of the subject before the subject receives a therapy the depletes or reduces the level of the innate leukocyte.

38. The method of any one of claims 1-37, wherein the method results in (i) an increase in the number of the innate leukocytes in the subject; (ii) an increase in the number of functional innate leukocytes in the subject; (iii) a reduction in the incidence, severity, and/or duration of an opportunistic infection in the subject; (iv) a reduction in the incidence, severity, and/or duration of a symptom of neutropenia in the subject; (v) a reduction in the incidence, severity, and/or duration of a symptom of an immunodeficiency-associated complication in the subject; (vi) an increase in the level of tissue regeneration in the subject; (vii) an increase in the therapeutic efficacy of a therapy that depletes or reduces the innate leukocyte in the subject; (viii) an increase in the degradation of the scaffold in the subject; and/or (ix) an increase in the release of a detectable agent, an active agent, and/or an additional active agent from the scaffold in the subject.

39. The method of any one of claims 1-38, wherein the subject has or is receiving systemic G-CSF and/or PEG-G-CSF.

40. The method of claim 39, wherein the administration of the composition is prior to, concurrently with, or subsequent to the systemic G-CSF and/or PEG-G-CSF.

41. The method of any one of claims 1-41, further comprising administering to the subject systemic G-CSF and/or PEG-G-CSF.

42. The method of any one of claims 1-41, wherein (i) the subject has or is at risk of developing anti-PEG antibody (APA)-mediated rapid clearance; (ii) the subject has pre- existing or induced anti-PEG antibody (APA)-mediated rapid clearance; and/or (iii) the subject has failed or is at risk of failing to respond to systemic G-CSF and/or PEG-G-CSF.

43. A method of treating a subject for cancer in need thereof, wherein the subject is undergoing chemotherapy or radiotherapy, comprising administering to a subject suffering from depleted or reduced innate leukocytes, wherein the composition comprises a biodegradable scaffold and a cytokine that enhances the generation of the innate leukocyte; assessing the levels of the innate leukocyte in the subject; administering chemotherapy or radiotherapy to the subject wherein the levels of innate leukocyte have attained a reference level following administration of the composition.

44. The method of claim 95, wherein the innate leukocytes are neutrophils.

45. The method of claim 95, wherein the cytokine is G-CSF.

46. The method of claim 95, wherein the subject is suffering from depleted or reduced innate leukocytes as a result of previous exposure to chemotherapy or radiotherapy.

47. The method of claim 95, wherein the reference level is a standardized level, optionally, (i) wherein the reference level is the level of the innate leukocyte of the subject before depletion of the level of the innate leukocyte; and or (ii) the reference level is the level of the innate leukocyte of the subject before the subject receives a therapy the depletes or reduces the level of the innate leukocyte.

48. An injectable composition, comprising a scaffold composition comprising hyaluronic acid, and (i) an active agent that increases the number of and/or modulates the activity of an innate leukocyte; and/or (ii) a detectable agent that allows for assessment of degradation of the scaffold composition and/or assessment of the levels of functional innate leukocytes in vivo.

49. The injectable composition of claim 48, comprising both the active agent and the detectable agent.

50. The injectable composition of claim 48 or 49, wherein the innate leukocytes are neutrophils.

51. The injectable composition of any one of claims 48-50, wherein the active agent is G- CSF.

52. A method for detecting immune recovery in a subject having a deficiency in levels of functional innate leukocytes, comprising administering the injectable composition of any one of claims 48-51 and assessing the degradation of the scaffold composition and/or levels of functional innate leukocytes in vivo.

53. A method of modulating the activity of an innate leukocyte, restoring levels of functional innate leukocytes, reconstituting the levels of functional innate leukocytes and/or enhancing the regeneration of functional innate leukocytes in a subject in need thereof, wherein the subject has a deficiency in levels of functional innate leukocytes, the method comprising administering to the subject the composition of claims 48-51.