CN109248343A - A kind of self assembly polypeptide hydrogel bracket and preparation method thereof - Google Patents
A kind of self assembly polypeptide hydrogel bracket and preparation method thereof Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明公开一种自组装多肽水凝胶支架，包括骨架，以及修饰于所述骨架表面的自组装多肽水凝胶，所述骨架的材质为具有疏水表面的高分子聚合物，所述多肽为具有FE和FK结构单元的多肽。该多肽自组装水凝胶支架，不仅同时具备优良的刚性和表面生物相容性，还能够促进间充质干细胞的成骨分化，以及软骨细胞自身分化过程中表型的维持，实现骨软骨缺损模型中骨和软骨的分层再生。
The invention discloses a self-assembled polypeptide hydrogel scaffold, comprising a skeleton, and a self-assembled polypeptide hydrogel modified on the surface of the skeleton. The material of the skeleton is a high molecular polymer with a hydrophobic surface, and the polypeptide is Polypeptides with FE and FK building blocks. The polypeptide self-assembled hydrogel scaffold not only has excellent rigidity and surface biocompatibility at the same time, but also can promote the osteogenic differentiation of mesenchymal stem cells and maintain the phenotype during the self-differentiation of chondrocytes, so as to achieve osteochondral defects Hierarchical regeneration of bone and cartilage in a model.
Description
Technical field
The invention belongs to bone tissue reparation and rebuild field, and in particular to a kind of self assembly polypeptide hydrogel organizational project branch
Frame and preparation method thereof.
Background technique
The kinematic system of human body is mainly made of bone, joint and skeletal muscle three parts, and joint is as movement hinge to body
Action play an important role, including buffering stress, transfer charge, reduce friction etc., therefore determine facet joint complex and smart
Thin structure.With getting worse for population aging and problem of obesity, suffers from arthritic number and be increasing every year, according to system
Meter, China has 250,000 people to need to carry out knee joint and hip replacement every year, so the reparation of joint injury comes one in recent years
It is directly the hot spot of research.Currently, clinically the treatment method of articular cartilage reparation mainly has micro fractures method, Cartilage transplantation
(ACT) it is transplanted with allogeneic cartilage.Although these methods successfully alleviate the pain of patient, improve the function of cartilage,
But there are donor source deficiency, surgical procedure complexity, cartilage shortage natural cartilage structure of rejection, reparation etc. are scarce for the above method
Point.These defects possibly even hinder the prolonged application of these treatment methods clinically.
The appearance of tissue engineering technique solves deficiency present in bone defect traditional treatment mode.Bone tissue engineer packet
Include three elements: bracket, signal factor and cell.Wherein bracket not only to cell, organize physical connection and supporting function, and
And important function also has been played in the various functional activities for adjusting cell.There are many preparation method of bone tissue engineering scaffold,
The bone tissue engineering scaffold of middle 3D printing technique preparation is tied in bracket personalization, accuracy, mechanical strength, hole adjusting, space
There is unique advantage in terms of structure complexity.Using biodegradable materials such as medical high polymer, bioceramic, bioactivity glass,
By means of CAD (Computer-aided design, CAD), finite element analysis (Finite element, FE)
Etc. advanced manufacturing technologies, more can accurately prepare matching defective region shape, structure-controllable porous support.Using a group weaver
The process that journey technology repairs cartilage is usually: the cartilage cell of in-vitro separation amplification and growth factor or bioactive substance are answered
It closes, is then introduced into certain bracket, then the cartilage of the method repair deficiency by operation or minimally invasive injection.Currently, porous support, fibre
The bracket of various structures including dimensional scaffold, hydrogel and microcarrier is used for the research and application of repair of cartilage.
However, the material of good biocompatibility, such as hydrogel scaffold, rigidity is often poor in existing timbering material,
Mechanical strength is low, and large segmental bone defect and weight bearing area bone defect are difficult to provide effective support.And the preferable material of rigidity, such as
Polycaprolactone (PCL), hydrophobicity is stronger, and material surface lacks cell adhesion site, causes cell compatibility poor, is applied to
Weight bearing bone may cause bone nonunion.
Cell culture is easier to transport on three-dimensional rack, and will not seriously damage cell-material and cell-ECM it
Between interaction, so as to provide new approach for accurate RESEARCH ON CELL-BIOLOGY.
The PCL bracket (and the polymeric stent of other 3 D-printings such as PLLA, PLGA, PLLA-PLGA) of 3D printing,
The fibre diameter of its bracket is about between 10~500 microns, and the size is similar to most cells (5~20 microns of diameter).Cause
This, even if cell is attached to the fiber surface of these brackets still in the case where scaffold fibers have certain circular arc curvature
Closer to spreading over 2D plane environment, rather than three-dimensional environment truly.
In addition, the growth of cell culture in the environment depends on the generation, exchange, accumulation of numerous biomolecule.3D printing
Scaffold fibers between micropore between 10~700 microns (cross sections), usually the 1000 of the size of biomolecule~
100000 times, therefore these biomolecule, nutriment such as vitamin, amino acid, protein or drug can be in brackets and body fluid
Exchange process in it is rapidly losing, causing to cultivate cells growth activity on external supporting reduces and regenerates in body tissue difficult.
Summary of the invention
For the above-mentioned deficiency of existing osteochondral defect recovery technique, the present invention provides a kind of three-dimensional bionic self assembly polypeptide
Hydrogel scaffold and preparation method thereof.It is raw to be not only provided simultaneously with excellent rigidity and surface for the self-assembling polypeptide hydrogel scaffold
Object compatibility, additionally it is possible to promote the dimension of phenotype in the Osteoblast Differentiation and cartilage cell itself atomization of mescenchymal stem cell
It holds, realizes the layered regeneration of bone and cartilage in osteochondral defect model.
To achieve the above object, the present invention adopts the following technical scheme that:
A kind of self assembly polypeptide hydrogel bracket, including skeleton, and modification is in the self assembly polypeptide water-setting on the skeleton surface
Glue, the material of the skeleton are the high molecular polymer with hydrophobic surface, and the polypeptide is with FE and FK structural unit
Polypeptide, preferably with the polypeptide of FEFEFKFK structural unit.The self assembly polypeptide hydrogel has three-dimensional space network class
Extra-cellular matrix structure can promote sticking in compound rest, being proliferated for mesenchymal stem cell and cartilage cell, promote bone
Bone marrow-drived mesenchymal stem breaks up in compound rest, and chondrocyte phenotype is promoted to maintain, and promotes compound rest in knee joint femoral
Condyle osteochondral defect model integration bone and cartilage layering are repaired.
Self assembly polypeptide is similar to the gel stent of natural extracellular matrix (ECM) as a kind of structure, can be water-soluble
Mesh nano fiber is spontaneously assemble into liquid, the polypeptide fibers of this High water cut show high surface of epitopes density, so that
They become the ideal matrix for promoting cell activity.Since cartilage cell belongs to attachment dependent form cell, they are in porous branch
It needs the surface for being attached on these materials that could grow in frame and micrometer fibers bracket, typically exhibits out the flat sample form sprawled.
And cartilage cell in nano fiber scaffold and hydrogel scaffold then at round or ellipse form, this and its in natural cartilage base
In matter more closely, thus be more advantageous to maintain cartilage cell normal phenotype.Rounded or oval dry thin of growth conditions
Born of the same parents are more likely to Chondrocyte Differentiation.In addition, the aqueous environment of hydrogel scaffold is more advantageous to protection cell and volatile
Drug living such as polypeptide, protein, oligonucleotide and DNA etc. is also beneficial to transport nutrition and cell secretory product etc..
The basic structure of peptide molecule with FE and FK structural unit is by hydrophilic radical paddy electrically charged under Physiological Medium
Propylhomoserin, lysine and uncharged hydrophobic group phenylalanine are constituted.This polypeptide is the polypeptide sequence of β-pleated sheet, its property
The hard to bear adjusting to external environment of mass-energy, so it is consistent with the engineering properties of β-pleated sheet peptide molecule, plastic dynamical phase.Have
FE and FK structural unit has hydrophilic, hydrophobic double lamellar structures, and nanofibrous structures are self-assembled into Physiological Medium, are being faced
Boundary at gum concentration on, formed have some strength hydrogel.This Self-Assembled can with skeleton part formed compared with
Strong hydrophobic forces, and then stable bond is on skeleton surface；Meanwhile the self assembly polypeptide water-setting with FE and FK structural unit
Hydrophilic lamella in glue is exposed on the outside of composite construction, so that compound rest hydrophily with higher, can be obviously improved thin
Adherency and proliferation of the born of the same parents on framework material surface.
Preferably, the skeleton has porous structure.
Preferably, the skeleton is to be spliced framework by fibre bundle and obtained.It is furthermore preferred that the fibre bundle intersection, accumulation shape
At porous structure.
Preferably, the skeleton is obtained by 3D printing.
Preferably, the material of the skeleton is polycaprolactone (PCL), poly lactide-glycolide acid (PLGA), poly- second
Alkyd (PGA) or polylactic acid (PLA).
Preferably, the molecular weight of the high molecular polymer is 4000 ~ 240000.Preferably, the polycaprolactone (PCL)
Molecular weight be 10000 ~ 80000, the molecular weight of the polylactic acid (PLA) is 5000 ~ 40000, the poly lactic-co-glycolic acid
The molecular weight of copolymer (PLGA) is 4000-240000.
It is a further object of the present invention to provide the preparation methods of the self assembly polypeptide hydrogel bracket, include the following steps:
(1) skeleton with specific shape is prepared as needed；
(2) polypeptide hydrogel is prepared；
(3) under the conditions of the dissolved colloidal state of the polypeptide hydrogel, the skeleton of step (1) preparation is put into the polypeptide hydrogel
In, it cools down, so that the colloidal sol of the polypeptide switchs to gel state and is equably attached to the skeleton surface, adjusts later solidifying later
Glue pH is 6.8 ~ 7.2.
Wherein, the shape of the polymer backbone of preparation is determined according to the shape that affected part needs, and prepares the side of polypeptide hydrogel
Method is the prior art.
Further, step (1) includes the following steps:
Fibre bundle is made by 3D printing technique in high molecular polymer with hydrophobic surface by (1-1)；
Multiple fibre bundle joggle trusses as needed are configured to have the generally specific shape of multi-pore structure by (1-2)
Skeleton.
Further, the diameter of the fibre bundle is 300 ~ 500 microns.
Further, step (2) includes the following steps:
A certain amount of polypeptide with FE and FK structural unit is soluble in water, acidic sol-gel is made, and heat and guaranteed
Fully dissolved.
Further, the concentration of polypeptide hydrogel described in step (2) is 0.5% ~ 4.0%(wt).
Further, dissolved colloidal state condition described in step (3) are as follows: temperature is controlled at 80 ~ 90 DEG C.
Further, the temperature of cooling described in step (3) is room temperature.
Further, the method for pH of latex gel is adjusted described in step (3) are as follows: the NaOH aqueous solution of 1 mol/L is added.
Bone defect form of the shape of self assembly polypeptide hydrogel bracket of the present invention according to different areas to be repaired
3D printing individual character manufacturing is carried out, or is fabricated to the bracket of fixed profile by 3D printing.
The beneficial effects of the present invention are:
(1) the bone tissue reparation bracket of suitable intensity: the skeleton part of bracket of the present invention is that have by the way that 3D printing is prefabricated
The layer-by-layer accumulation of different levels and angle and multi-pore structure made of splicing framework, construct the bone of suitable bone defect healing intensity
Frame, each layer fiber in hole can intersect in the range of 0 ~ 180 ° and accumulate and, and bracket middle skeleton of the present invention
Mechanical strength has adapted to the biomethanics of bone tissue under different levels, can mediate the regeneration for completing bone tissue.
(2) three-dimensional bionic surface modification: the self-assembling polypeptide water-setting used in the present invention with FE and FK structural unit
There is glue the micro-structure of class extracellular matrix to be adjustable skeleton surface roughness properties, regulate and control the cell adherence performance of skeleton.Using
Self-assembling polypeptide hydrogel is surface modified, and is not only simple and obviously improves the hydrophily and life of skeleton, especially PCL
Object compatibility.And the class extra-cellular matrix structure of the self-assembling polypeptide hydrogel with FE and FK structural unit can promote cell
Compatibility, maintain chondrocyte phenotype, promote the differentiation of mesenchymal stem cell, and extracellular base can be promoted
The deposition of matter, to maintain good bone repair of cartilage environment.Meanwhile by changing self-assembling polypeptide hydrogel in manufacturing process
Time, concentration are modified, can further regulate and control the load capacity of rack surface Self-Assembled modification, and then regulate and control compound rest
Biological effect.
(3) good Bone Ingrowth characteristic and biological safety: self assembly polypeptide hydrogel compound rest of the invention has
The local micro-loop that good biocompatibility can be provided with conducive to stem cell adherency, amplification, Osteoblast Differentiation and bone matrix accumulation
Border.Meanwhile the modification of the self-assembling polypeptide hydrogel with FE and FK structural unit can further improve the hydrophilic of rack surface
Property and biocompatibility.It is compound to realize defective region efficient repair process for a long time, meanwhile, porous structure be conducive to nutrition at
The exchange divided, and then can promote growing into for new bone.The entire biological safety for repairing system is considerably higher compared with other modification schemes,
Skeletonization is obviously improved at cartilage activity.
Self assembly polypeptide hydrogel bracket provided by the invention, also fills while having existing bone renovating material advantage
The performance of 3D printing technique, timbering material itself has been waved in distribution, so that the present invention has simple and reliable for structure, shape and micro-structure
Controllably, surface modification simple and effective, mechanical property is reliable, and bioactivity and highly-safe, implantation convenience, wound are small, at low cost
The advantages of, it can be used for the repairing and treating of osteochondral defect after bone wound, bone tumour, infection of bone.
(4) self assembly polypeptide hydrogel bracket provided by the present invention compares other methods, such as chemical synthesis process system
Standby bracket generates outside the by-product for being difficult to remove, additionally it is possible in addition to side reaction does not occur so that obtained bracket itself has
The effect of the three-dimensional space network class extra-cellular matrix structure of standby gel, plays the excellent performance of polypeptide hydrogel, to bracket week
Enclose the environment of a class extracellular matrix.
Firstly, the polypeptide used in the present invention with FE and FK structural unit is not have bioactive functions more
Peptide, such as the polypeptide with biological effect such as osteogenic induction effect polypeptide BMP-2 or rush cell adhesion peptide RGD can be played directly
Drug effect, the present invention in, with FE and FK structural unit polypeptide by being self-assembly of nanofiber water-setting in Physiological Medium
Glue this kind ECM structure, realizes a series of beneficial effects, comprising:<1>promotes mesenchymal stem cell and cartilage cell
Stick in compound rest, be proliferated；<2>mesenchymal stem cell is promoted to break up in compound rest；<3>promote cartilage cell's table
Type maintains；<4>compound rest is promoted to repair in rabbit knee condyle of femur osteochondral defect model integration bone and cartilage layering.
The bone repair of cartilage integrated bracket of existing high molecular material preparation is usually directed to high molecular material rack body
The polypeptide or protein material of structure and active function.The latter's (polypeptide or protein material of active function) and high score
The complex method of sub- stock support main structure has chemical bonding, is bonded the molecules of bioactive functions a kind of to material quotient,
Promote proliferation directly to play, promote bone uptake or promote the effect of differentiation.Using the method for chemical bonding biotic factor, reach a kind of life
Object activity, tends not to complete by one-step method, multistep is needed to complete, if you need to realize a variety of biological functions, as promoted to stick and promoting to increase
The double effects grown then need multiple chemical experiment to be bonded different biotic factors respectively.Not only production efficiency is lower for the method, and
And a series of chemical reagent being added in reaction process, the risk of cytotoxicity is not only increased, and be difficult to remove.
In addition, the bracket obtained by the method for being chemically bonded biotic factor, can not achieve the integration of osteochondral defect
It is repaired with layering.This is because caused by the globality and unicity of bonding factor effect, and it is in the bone of different physiological sites
Different biotic factor signals is responded with cartilaginous tissue, the integrally provided single stimulation of bracket is not able to satisfy the tissue of different parts
Reparation demand, so whole biological effect cannot reach desired layering repairing effect.
In the design, the polypeptide hydrogel that being used alone, there is the polypeptide of FE and FK structural unit to be formed is provided not only
Promote the effect that cell Proliferation is sticked, and realizes the effect that the layering of bone cartilage is repaired.In the design, there is FE and FK structure list
The polypeptide hydrogel of member provides water-wetted surface for PCL bracket, is conducive to sticking and accumulating for albumen, to make medulla mesenchyma
Stem cell and cartilage cell it is stronger attach to rack surface；In addition, the polypeptide hydrogel with FE and FK structural unit
Class ECM structure is formd, so that mesenchymal stem cell and cartilage cell obtain bionical living environment, to promote
Mesenchymal stem cell breaks up in compound rest and chondrocyte phenotype maintains, and then guarantees for intracorporal regeneration
Good cell origin；In the polypeptide hydrogel of class ECM, mesenchymal stem cell and cartilage cell are enhanced extracellularly
The generation ability of matrix, a large amount of osteoblast epimatrix such as type glue that wherein mesenchymal stem cell Osteoblast Differentiation generates
Original, in lower osteoplaque, cartilage cell produces cartilage cell epimatrix during the growth process for a large amount of accumulations, and a large amount of accumulations are in cartilage
Layer, these extracellular matrixs maintain the lower osteoplaque physiological environment different with cartilage layers respectively, to promote the proliferation of different cells
Differentiation, to reach the layering repairing effect of bone and cartilage.
Detailed description of the invention
Fig. 1 is cartilage cell prepare in PCL bracket and embodiment 1 self assembly polypeptide hydrogel bracket 24 hours stick
The result of situation and dead cell ratio living；Wherein, A figure is PCL bracket, B figure be hydrogel concentration be 0.5% be prepared answer
Bracket is closed, it is 1.5% compound rest being prepared that C figure, which is hydrogel concentration, and D figure is that hydrogel concentration is 3.0% to be prepared
Compound rest.
Fig. 2 is the self assembly polypeptide hydrogel that scanning electron microscope sem characterization cartilage cell prepares in PCL bracket and embodiment 1
The characterization result of 3 days growing states of bracket, wherein E figure is PCL bracket, and F figure is that hydrogel concentration is 0.5% to be prepared
Compound rest, it is 1.5% compound rest being prepared that G figure, which is hydrogel concentration, and H figure is that hydrogel concentration is 3.0% to be prepared into
The compound rest arrived.
Fig. 3 is cartilage cell 1 on self assembly polypeptide hydrogel bracket (* S-PCL) prepared by PCL bracket and embodiment 1 ~
7 days proliferative conditions.
Fig. 4 is the self assembly polypeptide hydrogel bracket (* S-PCL) that mescenchymal stem cell is prepared in PCL bracket and embodiment 1
Upper 1 ~ 7 day proliferative conditions.
Fig. 5 is the self assembly polypeptide hydrogel bracket (* S-PCL) that mescenchymal stem cell is prepared in PCL bracket and embodiment 1
The expression of osteogenesis gene and the characterization of alkaline phosphatase activities in the osteogenic differentiation process of upper 7 day and 14 days.
Fig. 6 is cartilage cell 7 on self assembly polypeptide hydrogel bracket (* S-PCL) prepared by PCL bracket and embodiment 1
The maintenance situation of the cartilage phenotype gene of it and 14 days and the cumulant of glycosaminoglycan (GAG).
Fig. 7 is sarranine self assembly polypeptide hydrogel bracket (the * S- that fastly prepared by green staining evaluation PCL bracket and embodiment 1
PCL) implantation rabbit knee osteochondral defect model 8 weeks and 12 weeks cartilages and subchondral bone repairs situation.
Specific embodiment
Embodiment 1
1.3D prints PCL skeleton:
The quick extrusion molding of FDM, the heating system of 3D printing, which is warming up to 100 DEG C of PCL particles (molecular weight 10000 ~ 80000), to be become
Viscous fluid squeezes out shaping fiber beam (300 ~ 500 microns of diameter range), passes through the spelling of the different levels and angle of fibre bundle
It connects framework and obtains 3D printing skeleton.Each layer fiber intersects in the range of 0 ~ 180 ° and accumulates 0 ~ 60 ~ 120 ° of triangle knots of formation
Structure, skeleton aperture are 500 microns, and porosity is 85% or more.
2. preparing the self-assembling polypeptide hydrogel-colloidal sol with FE and FK structural unit:
FEFEFKFK self assembly polypeptide (SAP) is dissolved in distilled water, acidic sol-gel is made, ultrasound is vortexed, 80 DEG C of heating 1
H guarantees to be completely dissolved, and the polypeptide hydrogel that concentration is 0.5%wt, 1.5%wt and 3.0%wt is made respectively.
3. Self-Assembled is coated with PCL skeleton
In dissolved colloidal state FEFEFKFK hydrogel, prefabricated PCL skeleton is quickly put into, is vortexed, it is cooling to quickly remove room temperature.It is cooling
Process switchs to gel state process with FEFEFKFK colloidal sol, and FEFEFKFK hydrogel is spread evenly across PCL skeleton surface.
4.pH induces high-intensitive self assembly PCL- self assembly polypeptide hydrogel compound rest
After FEFEFKFK hydrogel is spread evenly across PCL rack surface, 1 mol/L NaOH is added, being adjusted to matrix gel pH is in
7.0±0.2.Under neutrallty condition, the enhancing of Self-Assembled mechanical performance enhances with PCL active force, and stabilization is compound in PCL bone
Frame.
5. detecting the biological property of PCL- self assembly polypeptide hydrogel compound rest
(1) cell Proliferation.Bone marrow mesenchymal stem cells and cartilage cell are carried on PCL- self assembly polypeptide hydrogel respectively
Compound rest and PCL bracket utilize the proliferation of CCK-8 kit detection cell.Cell proliferation results show two kinds of cells in water
Gel-PCL compound rest cultivation effect enhances and has significant difference with PCL bracket.
(2) cell differentiation.Bone marrow mesenchymal stem cells and cartilage cell are carried on PCL- self assembly polypeptide water respectively
Gel compound rest and PCL bracket are stimulated 7 days and 14 days with Osteogenic Induction Medium, detect Osteoblast Differentiation phenotype genes
(RUNX-2, COL-1, OPN, OCN) and alkaline phosphatase activities.Bone marrow mesenchymal stem cells exist Osteoblast Differentiation as the result is shown
PCL- self assembly polypeptide hydrogel compound rest differentiation degree enhances, PCL bracket under the more identical incentive condition of gene expression dose
There are~5 times of risings.
Rabbit cartilage cell is carried on to PCL- self assembly polypeptide hydrogel compound rest and PCL bracket respectively, with common
The culture of DMEM culture medium 7 days and 14 days, detect cartilage phenotype gene (SOX-9, COL-2, ACAN) and glycosaminoglycan content.It is soft
Cartilage cell dramatically increases bone cell differentiation in the expression of PCL- self assembly polypeptide hydrogel compound rest phenotype genes as the result is shown,
PCL bracket has~3 times of risings under the more identical incentive condition of gene expression dose.
6. the osteochondral defect for detecting PCL- self assembly polypeptide hydrogel compound rest repairs characteristic
At the PCL- self assembly polypeptide hydrogel compound rest implantation in rabbit condyle of femur osteochondral defect for being 5mm by diameter 4mm height,
Materials row histology and iconography CT examination, detect its skeletonization and at cartilage efficiency after February, March.As the result is shown compared with
It is not implanted into bracket and implantation PCL bracket group, PCL- self assembly polypeptide hydrogel compound rest has more bone tissue to grow into, and has
One transparent neocartilage tissue grows into and substitutes timbering material.
Embodiment 2
The present embodiment 2 and the difference of embodiment 1 be only that, skeleton part uses molecular weight for 5000 ~ 40000 PLA, and prepares
Polypeptide hydrogel concentration be 2.0%wt, polypeptide used be FEFKFEFK.
Embodiment 3
The present embodiment 3 and the difference of embodiment 1 be only that, skeleton part uses molecular weight for 4000 ~ 10000 PLGA, and makes
The concentration of standby polypeptide hydrogel is 4.0%wt, and polypeptide used is FEFEFKFKFEFEFKFK (FEK16).
Embodiment 4
The present embodiment 4 and the difference of embodiment 1 be only that, skeleton part use molecular weight for 80000 ~ 240000 PLGA, and
The concentration of the polypeptide hydrogel of preparation is 1.0%wt.
Claims (10)
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Application publication date: 20190122 |