Silvia Scaglione
National Research Centre, IEIIT, Department Member
- Tissue Engineering, Biomaterials, Biomaterials Engineering, Lab On A Chip, Materials Science & Engineering, Semiconductor Nanostructures, and 14 moreHydrogels, Regenerative Medicine, Biopolymers, Nano Composites, Biodegradable polymer composites, Biocomposites, Biomaterials and tissue engineering scaffolds, Natural Polymers, Polymer Composites, Biomaterials and Tissue Engineering, Bioreactors, Stem cell and Regenerative medicine, Composite Scaffolds for Bone Tissue Engineering, and Scaffold Fabrication and Tissue Engineering with Nano Relatededit
- She received the Ph.D. in Bioengineering at the University of Genoa (I) in 2005. In 2004 she was Visiting Scientist a... moreShe received the Ph.D. in Bioengineering at the University of Genoa (I) in 2005. In 2004 she was Visiting Scientist at the University Hospital of Basel (CH). Since 2010 Scaglione is permanent Researcher (Senior researcher since 2021) at National Council of Research (CNR). She is founder and chief scientist of React4life, an Italian biotech company that develops organ on chip technologies for medical research, winning several international projects and awards, such as the Innovation Radar award from EU as best Health technology. Scaglione is author of more than 80 international peer-reviewed papers, book chapters, author of 7 patents. She has been tutor of more than 50 master/PhD students, responsible and reviewer of several national/international research projects. Scaglione is currently PI of a Future Emerging Technology European H2020 project on a spontaneous cancer model in vitro (B2B).She is Ambassador of the European Innovation Council, and Gamma Donna Ambassador since 2021.edit
ABSTRACT A wide range of software has been moving to Cloud platforms, except for 3D applications, which require hardware (access to high-end GPU1) and software (use of libraries for 3D graphics like OpenGL or DirectX) not yet supported.... more
ABSTRACT A wide range of software has been moving to Cloud platforms, except for 3D applications, which require hardware (access to high-end GPU1) and software (use of libraries for 3D graphics like OpenGL or DirectX) not yet supported. Therefore, we here present an innovative technology, enabling “3D Clouds”, i.e. Clouds able to host 3D applications and provide them “as a service”. Achieving this goal can be very useful in Biomedicine and Life Sciences, where 3D visualization and image analysis play a key role. End users are immediately empowered by taking full advantage of high-end graphics cards, fast I/O performance and large memory nodes hosted in "Public or Private 3D Cloud", rather than waiting for the next upgrade of the graphics workstations. Even if the technology supports a wide range of 3D applications, we here present a case study in molecular modeling field, considering crucial aspects of security and data management.
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Spontaneous processes in an aqueous solution of body simulated fluid (SBF) were monitored in closed vessel for a period of 1 month at 310 K, at atm pressure, and initial pH of 7.2, both with and without exposure to a square pulsed... more
Spontaneous processes in an aqueous solution of body simulated fluid (SBF) were monitored in closed vessel for a period of 1 month at 310 K, at atm pressure, and initial pH of 7.2, both with and without exposure to a square pulsed extremely low frequency electromagnetic fields (EM-ELF) of 250 microT, repeated at 75 Hz. The most important findings are that the SBF surface tension (gamma), evaluated under the EM-ELF field, is lower than the corresponding value measured without EM-ELF at any time. Furthermore, the pH of the exposed SBF is always more basic than that of the unexposed solution. As a consequence, when the EM-ELF is applied, calcium phosphate salts do not precipitate from the SBF solution for a period as long as 30 days. Behind all these experimental evidences there is only one mechanism: the vaporisation from the SBF-air interface of the CO(2)(aq) dissolved into the aqueous electrolyte solution. Thermodynamic analysis of these results establish that, at any given time, the difference, Delta, between the measured surface tensions with and without EM-ELF applied, gives the work of the electromagnetic forces to change the extent at which the CO(2)(aq) adsorbs at the liquid-air interface. It has been demonstrated that the work supply per second and per unit of area by the electromagnetic forces, 3.73 x 10(-10) mJ/s cm(2), is very near to the experimental slope in the plot Delta vs. t 1.7 x 10(-10) mJ/s cm(2). This leads to the conclusion that the EM-ELF fields have an interfacial effect on the concentration value of the CO(2) (aq) at the SBF-air interface. Because of that, the EM-ELF field is enhancing the CO(2) vaporisation rate; thus any other steps, which are a consequence of this mechanism, are changing. These results allow explanation of previous experiments concerning the precipitation of calcium carbonate from flowing hydrogen carbonate aqueous solution in the temperature range 353-373 K at a pressure of 0.1 MPa under the effect of static magnetic fields.
Research Interests: Engineering, Materials Science, Water, Carbon Dioxide, Bioelectromagnetics, and 15 moreMedicine, Adsorption, Biological Sciences, Computer Simulation, Electromagnetic Fields, Electromagnetic Field, Surface Tension, Solutions, Surface Properties, Aqueous Solution, Body Fluids, Electrolyte, Volatilization, Psychology and Cognitive Sciences, and Vaporization
In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal... more
In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore, the development of novel approaches is fundamental for better evaluating novel anti-cancer treatments. Here, a multicompartmental organ-on-chip (OOC) platform was adopted to fluidically connect 3D ovarian cancer tissues to hepatic cellular models and resemble the systemic cisplatin administration for contemporarily investigating drug efficacy and hepatotoxic effects in a physiological context. Computational fluid dynamics was performed to impose capillary-like blood flows and predict cisplatin diffusion. After a cisplatin concentration screening using 2D/3D tissue models, cytotoxicity assays were conducted in the multicompartmental OOC and compared with static co-cultures and dynamic sing...
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In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer treatment. In a relevant percentage of patients, however, clinical benefits are lower than expected, pushing researchers to deeply analyze the... more
In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer treatment. In a relevant percentage of patients, however, clinical benefits are lower than expected, pushing researchers to deeply analyze the immune responses against tumors and find more reliable and efficient tools to predict the individual response to therapy. Novel tissue engineering strategies can be adopted to realize in vitro fully humanized matrix-based models, as a compromise between standard two-dimensional (2D) cell cultures and animal tests, which are costly and hardly usable in personalized medicine. In this review, we describe the main mechanisms allowing cancer cells to escape the immune surveillance, which may play a significant role in the failure of immunotherapies. In particular, we discuss the role of the tumor microenvironment (TME) in the establishment of a milieu that greatly favors cancer malignant progression and impact on the interactions with immune cells. Then...
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The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment,... more
The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous “extravasation” process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect ...
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Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellular phenomena both in normal and pathological conditions. In particular, mechanical stimuli not less than chemical ones have a relevant role on... more
Three-dimensional (3D) cell cultures represent fundamental tools for the comprehension of cellular phenomena both in normal and pathological conditions. In particular, mechanical stimuli not less than chemical ones have a relevant role on cell fate, cancer onset and malignant progression. Here, we realize mechanically tuned alginate hydrogels for studying the role of substrate elasticity on breast adenocarcinoma cells activity. Hydrogels Elastic Modulus (E) was measured via Atomic Force Microscopy and a remarkable range (20\u20134000 kPa) was obtained. A breast cancer cell line, MCF-7, was seeded within the 3D gels, on standard Petri and alginate-coated dishes (2D controls). Cells showed dramatic morphological differences when cultured in 3D vs. 2D, exhibiting a flat shape morphology in both 2D conditions, while they maintained within gels a circular, clusterorganized conformation similar to the in vivo one. In 3D culture, we observed a strict correlation between cells viability and...
<b>Copyright information:</b>Taken from "A Grid-based solution for management and analysis of microarrays in distributed experiments"http://www.biomedcentral.com/1471-2105/8/S1/S7BMC Bioinformatics 2007;8(Suppl... more
<b>Copyright information:</b>Taken from "A Grid-based solution for management and analysis of microarrays in distributed experiments"http://www.biomedcentral.com/1471-2105/8/S1/S7BMC Bioinformatics 2007;8(Suppl 1):S7-S7.Published online 8 Mar 2007PMCID:PMC1885859.
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Purpose The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing... more
Purpose The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing procedures onto three-dimensional scaffolds under controlled torsion/traction regimes. Methods Highly porous poly-caprolactone-based scaffolds were used as substrates colonized by fibroblast cells (3T3 cell line). Constructs were placed within the cylindrical culture chamber, clumped at the ends and exposed to controlled sequences of torsional stimuli (forward/back-forward sequential cycles of 100° from neutral position at a rate of 600°/min) through a stepper-motor; working settings were defined via PC by an easy user-interface. Cell adhesion, morphology, cytoskeletal fiber orientation and gene expression of extracellular matrix proteins (collagen type I, tenascin C, collagen type III) were evaluated after three days of torsional stimulation in the bioreac...
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Purpose of this study was the development of a 3D material to be used as substrate for breast cancer cell culture. We developed composite gels constituted by different concentrations of Alginate (A) and Matrigel (M) to obtain a... more
Purpose of this study was the development of a 3D material to be used as substrate for breast cancer cell culture. We developed composite gels constituted by different concentrations of Alginate (A) and Matrigel (M) to obtain a structurally stable-in-time and biologically active substrate. Human aggressive breast cancer cells (i.e. MDA-MB-231) were cultured within the gels. Known the link between cell morphology and malignancy, cells were morphologically characterized and their invasiveness correlated through an innovative bioreactor-based invasion assay. A particular type of gel (i.e. 50% Alginate, 50% Matrigel) emerged thanks to a series of significant results: 1. cells exhibited peculiar cytoskeleton shapes and nuclear fragmentation characteristic of their malignancy; 2. cells expressed the formation of the so-called invadopodia, actin-based protrusion of the plasma membrane through which cells anchor to the extracellular matrix; 3. cells were able to migrate through the gels and...
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Abstract The development of novel 3D systems is crucial for engineering artificial tissues since the behavior of cells growth on 2D cell culture substrates does not accurately reflect that of the physiological microenvironment. In this... more
Abstract The development of novel 3D systems is crucial for engineering artificial tissues since the behavior of cells growth on 2D cell culture substrates does not accurately reflect that of the physiological microenvironment. In this regard, desirable 3D composites should offer tunable structural and functional properties to support appropriate cellular growth and biomechanical loads. In this work, we realized 3D alginate hydrogels functionalized with graphene oxide (GO) nanosheets for the creation of cell laden hybrid materials with proper mechanical properties for tissue engineering applications. We monitored the mechanical proprieties of 2 wt% GO/Alg hydrogels up to one month demonstrating a significant improvement of the compressive elastic modulus reaching values of 300 KPa (6 times higher stiffness), which are close to those of articular tissues. This finding has been correlated to increased intermolecular hydrogen bonds over time between GO and Alg, observed through FT-IR analysis. Interestingly, we show that 3D GO/Alg hydrogels trigger cellular activity in vitro, as demonstrated by the statistically significant improvement of the viability of fibroblasts encapsulated in GO/Alg hydrogels and by the absence of cytotoxicity of suspended GO flakes. All these findings indicate that GO/Alg hydrogel is a promising material for articular tissue engineering, where biomechanical requirements are crucial.
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The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve... more
The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308 nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we found that nanotubes coating affects cell viability and proliferation demonstrating that TNT coatings enhance cell growth on the scaffolds by further improving their surface topography.
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ABSTRACT Vascular prostheses are widely used devices fundamental to avoid the effect of life-threatening diseases and defects. Besides a long experience in the fabrication of biomaterials for vascular applications, many issues still... more
ABSTRACT Vascular prostheses are widely used devices fundamental to avoid the effect of life-threatening diseases and defects. Besides a long experience in the fabrication of biomaterials for vascular applications, many issues still remain unattended. In particular, obtaining a bio-resorbable and bio-active scaffold is a challenge of paramount importance. We present a novel application in which a promising biodegradable polymer, poly-propylene fumarate (PPF), is printed using three dimensional laser-induced cross-linking micromachining device. To enhance the biological role of the scaffold, a bio-inspired approach was taken, by coating the surface of the PPF with elastin, the main constituent of the innermost layer of natural veins and arteries
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The design of new bioactive materials, provided with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;instructive... more
The design of new bioactive materials, provided with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;instructive properties&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and able to regulate stem cell behavior, is the goal for several research groups involved in tissue engineering. This new function, commonly reserved for growth factors, can lead to the development of a new class of implantable scaffolds, useful for accelerating tissue regeneration in a controlled manner. In this scenario, the likely most versatile and effective tools for the realization of such scaffolds are based on nano- and microtechnology. Here, we show how exploiting the electrostatic spinning (ES) technique for producing a nanofibrillar composite structure, by mimicking topographically the extracellular matrix environment, can influence the fate of human bone marrow mesenchymal stem cells, inducing osteogenic differentiation in the absence of chemical treatments or cellular reprogramming. Basic cues on the choice of the materials and useful experimental instructions for realizing composite nanofibrous scaffolds will be given as well as fundamental tips.
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Research Interests: Biomedical Engineering, Biology, Apoptosis, Medicine, Bone Regeneration, and 15 moreCollagen, Mice, Sheep, Animals, Three Dimensional Imaging, Light, Time Factors, Stromal Cells, Durapatite, Biocompatible Materials, Cell Survival, Mesenchymal Stromal Cells, Bone Marrow Cells, Biochemistry and cell biology, and Tissue Scaffolds
Research Interests: Chemistry, Biomedical Engineering, Tissue Engineering, Scanning Electron Microscopy, Composite Materials, and 15 moreBone Regeneration, Humans, Porosity, Magnesium, Differential scanning calorimetry, Mice, Animals, Medical Physiology, Clinical Sciences, Fourier transform infrared spectroscopy, Powders, Durapatite, Polyesters, Mesenchymal Stromal Cells, and bone development
Research Interests: Materials Science, Biomedical Engineering, Tissue Engineering, Scanning Electron Microscopy, Medicine, and 14 morePorosity, Cartilage, Mice, Animals, Scaffold, Medical Physiology, Tissue engineering and regenerative medicine, Interface, Clinical Sciences, Cattle, Articular Cartilage Wear, X Ray Microtomography, Bone and Bones, and Tissue Scaffolds
In modern biomaterial design the generation of an environment mimicking some of the extracellular matrix features is envisaged to support molecular cross-talk between cells and scaffolds during tissue formation/remodeling. In bone... more
In modern biomaterial design the generation of an environment mimicking some of the extracellular matrix features is envisaged to support molecular cross-talk between cells and scaffolds during tissue formation/remodeling. In bone substitutes chemical biomimesis has been particularly exploited; conversely, the relevance of pre-determined scaffold architecture for regenerated bone outputs is still unclear. Thus we aimed to demonstrate that a different organization of collagen fibers within newly formed bone under unloading conditions can be generated by differently architectured scaffolds. An ordered and confined geometry of hydroxyapatite foams concentrated collagen fibers within the pores, and triggered their self-assembly in a cholesteric-banded pattern, resulting in compact lamellar bone. Conversely, when progenitor cells were loaded onto nanofibrous collagen-based sponges, new collagen fibers were distributed in a nematic phase, resulting mostly in woven isotropic bone. Thus spe...
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Research Interests: Engineering, Materials Science, Tissue Engineering, Rheology, Biological Sciences, and 13 moreCell Differentiation, Humans, Calcium Phosphates, Perfusion, Fluid flow, Calcium Phosphate, Mechanical Stress, Model System, Stromal Cells, Osteoblasts, Bone Marrow Cells, Bone marrow stromal cells, and Cell culture techniques
In reconstructive surgery, implantable devices are used to supply a missing function. In tissue engineering, biomaterials serve to guide and eventually deliver cells and/or molecules where a tissue regenerative response is needed. The... more
In reconstructive surgery, implantable devices are used to supply a missing function. In tissue engineering, biomaterials serve to guide and eventually deliver cells and/or molecules where a tissue regenerative response is needed. The host organism always reacts to implants of any biomaterial, in some instances even triggering a local cascade of events called the foreign body response (FBR), whose mechanisms are well defined. What has yet to be completely unraveled are the biomarkers systemically mirroring the FBR and the regeneration processes, which would be helpful for assessing the therapeutic efficacy of the bioscaffold. Our goal was to identify a biomarker fingerprint of the systemic reaction of host response to bioscaffold implants. Different biomaterials chosen for their osteoconductive properties, including collagen, hydroxyapatite, in foam or granules, and poly-ɛ-caprolactone, were implanted in immunocompetent mice. We analyzed serum concentrations of cells and cytokines i...
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The development of a new family of implantable bioinspired materials is a focal point of bone tissue engineering. Implant surfaces that better mimic the natural bone extracellular matrix, a naturally nano-composite tissue, can stimulate... more
The development of a new family of implantable bioinspired materials is a focal point of bone tissue engineering. Implant surfaces that better mimic the natural bone extracellular matrix, a naturally nano-composite tissue, can stimulate stem cell differentiation towards osteogenic lineages in the absence of specific chemical treatments. Herein we describe a bioactive composite nanofibrous scaffold, composed of poly-caprolactone (PCL) and nano-sized hydroxyapatite (HA) or beta-tricalcium phosphate (TCP), which was able to support the growth of human bone marrow mesenchymal stem cells (hMSCs) and guide their osteogenic differentiation at the same time. Morphological and physical/chemical investigations were carried out by scanning, transmission electron microscopy, Fourier-transform infrared (FTIR) spectroscopy, mechanical and wettability analysis. Upon culturing hMSCs on composite nanofibers, we found that the incorporation of either HA or TCP into the PCL nanofibers did not affect c...
Research Interests: Chemistry, FTIR spectroscopy, Cell Adhesion, Extracellular Matrix, Cell Differentiation, and 15 moreHumans, Bone Tissue Engineering, Bone marrow, Cell Viability, Alkaline phosphatase, Bone Formation, Chemical Composition, Cell Proliferation, Growth Factor, Biocompatible Materials, Focal Point, Chemical Treatment, Human Mesenchymal Stem Cells, Gene Expression Regulation, and Fourier transform infrared
A stem cell is defined as a cell able to self-renew and at the same time to generate one or more specialized progenies. In the adult organism, stem cells need a specific microenvironment where to reside. This tissue-specific instructive... more
A stem cell is defined as a cell able to self-renew and at the same time to generate one or more specialized progenies. In the adult organism, stem cells need a specific microenvironment where to reside. This tissue-specific instructive microenvironment, hosting stem cells and governing their fate, is composed of extracellular matrix and soluble molecules. Cell-matrix and cell-cell interactions also contribute to the specifications of this milieu, regarded as a whole unitary system and referred to as &amp;amp;quot;niche&amp;amp;quot;. For many stem cell systems a niche has been identified, but only partially defined. In regenerative medicine and tissue engineering, biomaterials are used to deliver stem cells in specific anatomical sites where a regenerative process is needed. In this context, biomaterials have to provide informative microenvironments mimicking a physiological niche. Stem cells may read and decode any biomaterial and modify their behavior and fate accordingly. Any material is therefore informative in the sense that its intrinsic nature and structure will anyway transmit a signal that will have to be decoded by colonizing cells. We still know very little of how to create local microenvironments, or artificial niches, that will govern stem cells behavior and their terminal fate. Here we will review some characteristics identifying specific niches and some of the requirements allowing stem cells differentiation processes. We will discuss on those biomaterials that are being projected/engineered/manufactured to gain the informative status necessary to drive proper molecular cross-talk and cell differentiation; specific examples will be proposed for bone and cartilage substitutes.
Research Interests: Tissue Engineering, Regeneration, Stem Cells, Stem cell and Regenerative medicine, Biology, and 11 moreMedicine, Cell Differentiation, Humans, Cartilage, Medical Biotechnology, Biomaterials and tissue engineering scaffolds, Cell communication, Biocompatible Materials, Stem Cell Niche, Pharmacology and pharmaceutical sciences, and Tissue Scaffolds
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The first steps to be performed are noise reduction, shading correction, contrast, and edge enhancement. Depending on the noise sources and the hardware devices involved, images can be processed via software or hardware. Different... more
The first steps to be performed are noise reduction, shading correction, contrast, and edge enhancement. Depending on the noise sources and the hardware devices involved, images can be processed via software or hardware. Different standard image processing routines can be run and eventually adapted according to the kind of captured and stored data input (RGB, grey scale, or binary color space, multilayered or single-layered, compressed or uncompressed). For software data treatment, special algorithms (filters) are used or ...
Research Interests: Hematology, Computational Biology, Cancer, Biology, Cancer Research, and 14 moreStem Cell, Apoptosis, Medicine, Cell line, Mesenchymal stem cells, Humans, Mesenchymal Stem Cell, Phosphorylation, Cell Survival, Mesenchymal Stromal Cells, Gene expression profiling, Growth factor receptor, Hepatocyte Growth Factor, and Cardiovascular medicine and haematology
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Hydrogels have been widely used for articular tissue engineering application, due to their controllable biodegradability and high water content mimicking the biological extracellular matrix. However, they often lack the mechanical support... more
Hydrogels have been widely used for articular tissue engineering application, due to their controllable biodegradability and high water content mimicking the biological extracellular matrix. However, they often lack the mechanical support and signaling cues needed to properly guide cells. Graphene and its derivatives have recently emerged as promising materials due to their unique mechanical, physical, chemical proprieties [1]. Although not yet widely used for medical applications, preliminary works suggest that both structural and functional properties of polymeric substrates may be enhanced when combined with graphene oxide (GO) [2]. In this work, reinforced 3D GO/alginate (Alg) hydrogels have been realized and the opportunity of tuning hydrogels mechanical properties in relation to the required physiological needs has been investigated. After preparing GO nanosheets (Sigma Aldrich) aqueous suspension (1 mg/ml) by ultrasonic treatment, alginate (Manugel GMB, FMC Biopolymer) compos...
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Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates... more
Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates (clusters), which present a different potential to metastasize. The effects of the bloodstream-related physical constraints, such as hemodynamic wall shear stress (WSS), on CTC clusters are still unclear. Therefore, we developed, upon theoretical and CFD modeling, a new multichannel microfluidic device able to simultaneously reproduce different WSS characterizing the human circulatory system, where to analyze the correlation between SS and CTC clusters behavior. Three physiological WSS levels (i.e. 2, 5, 20 dyn/cm2) were generated, reproducing values typical of capillaries, veins and arteries. As first validation, triple-negative breast cancer cells (MDA-MB-231) were injected as single CTCs showing that higher values of WSS are correlated with a dec...
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Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target the heart and tailor the amount of drug dose by using a combination of magnetic... more
Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target the heart and tailor the amount of drug dose by using a combination of magnetic nanoparticles (NPs) and electromagnetic devices is a fascinating approach. Here, an electromagnetic device based on Helmholtz coils was generated for the application of low-frequency magnetic stimulations to manage drug release from biocompatible superparamagnetic Fe-hydroxyapatite NPs (FeHAs). Integrated with a fluidic circuit mimicking the flow of the cardiovascular environment, the device was efficient to trigger the release of a model drug (ibuprofen) from FeHAs as a function of the applied frequencies. Furthermore, the biological effects on the cardiac system of the identified electromagnetic exposure were assessed and by acute stimulation of isolated adult cardiomyocytes and in an animal model. The cardio-compatibility of FeHAs was also assessed ...
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Skin mechanical properties are usually measured considering the entire skin thickness and very little is known about the mechanical behaviour of individual skin layers. We propose atomic force microscopy (AFM) as a tool to quantify... more
Skin mechanical properties are usually measured considering the entire skin thickness and very little is known about the mechanical behaviour of individual skin layers. We propose atomic force microscopy (AFM) as a tool to quantify nanoscale changes in the biomechanical properties and ultrastructure of human papillary dermis exposed to different mechanical and physical stimuli. Samples from 3 human skin biopsies were studied: one stretched by obesity, one subjected to a high level of sun exposure and normal skin as control. Slices of the papillary dermis layer were harvested at controlled depths from each skin biopsy and 25 μm areas of each slice were imaged and D-periodicity of collagen fibres measured by AFM, together with their stiffness. Standard histological analysis was also carried out to correlate biochemical properties and their distribution with stiffness and topography. We obtained similar stiffness values between the sample affected by obesity and the control sample at a...
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The development of novel 3D systems is crucial for engineering artificial tissues since the behavior of cells growth on 2D cell culture substrates does not accurately reflect that of the physiological micro-environment. In this regard,... more
The development of novel 3D systems is crucial for engineering artificial tissues since the behavior of cells growth on 2D cell culture substrates does not accurately reflect that of the physiological micro-environment. In this regard, desirable 3D composites should offer tunable structural and functional properties to support appropriate cellular growth and biomechanical loads. In this work, we realized 3D alginate hydrogels functionalized with graphene oxide (GO) nanosheets for the creation of cell laden hybrid materials with proper mechanical properties for tissue engineering applications. We monitored the mechanical proprieties of 2 wt% GO/Alg hydrogels up to one month demonstrating a significant improvement of the compressive elastic modulus reaching values of 300 KPa (6 times higher stiffness), which are close to those of articular tissues. This finding has been correlated to increased intermolecular hydrogen bonds over time between GO and Alg, observed through FT-IR analysis....
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The really nontrivial goal of tissue engineering is combining all scaffold micro-architectural features, affecting both fluid-dynamical and mechanical performance, to obtain a fully functional implant. In thiswork we identified an optimal... more
The really nontrivial goal of tissue engineering is combining all scaffold micro-architectural features, affecting both fluid-dynamical and mechanical performance, to obtain a fully functional implant. In thiswork we identified an optimal geometrical pattern for bone tissue engineering applications, best balancing several graft needs which correspond to competing design goals. In particular, we investigated the occurred changes in graft behavior by varying pore size (300 μm, 600 μm, 900 μm), interpore distance (equal to pore size or 300 μm fixed) and pores interconnection (absent, 45°-oriented, 90°-oriented). Mathematical considerations and Computational Fluid Dynamics (CFD) tools, here combined in a complete theoretical model,were carried out to this aim. Poly-lactic acid (PLA) based samples were realized by 3D printing, basing on the modeled architectures. A collagen (COL) coating was also realized on grafts surface and the interaction between PLA and COL, besides the protein cont...
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Porous multiphase scaffolds have been proposed in different tissue engineering applications because of their potential to artificially recreate the heterogeneous structure of hierarchically complex tissues. Recently, graded scaffolds have... more
Porous multiphase scaffolds have been proposed in different tissue engineering applications because of their potential to artificially recreate the heterogeneous structure of hierarchically complex tissues. Recently, graded scaffolds have been also realized, offering a continuum at the interface among different phases for an enhanced structural stability of the scaffold. However, their internal architecture is often obtained empirically and the architectural parameters rarely predetermined. The aim of this work is to offer a theoretical model as tool for the design and fabrication of functional and structural complex graded scaffolds with predicted morphological and chemical features, to overcome the time-consuming trial and error experimental method. This developed mathematical model uses laws of motions, Stokes equations, and viscosity laws to describe the dependence between centrifugation speed and fiber/particles sedimentation velocity over time, which finally affects the fiber packing, and thus the total porosity of the 3D scaffolds. The efficacy of the theoretical model was tested by realizing engineered graded grafts for osteochondral tissue engineering applications. The procedure, based on combined centrifugation and freeze-drying technique, was applied on both polycaprolactone (PCL) and collagen-type-I (COL) to test the versatility of the entire process. A functional gradient was combined to the morphological one by adding hydroxyapatite (HA) powders, to mimic the bone mineral phase. Results show that 3D bioactive morphologically and chemically graded grafts can be properly designed and realized in agreement with the theoretical model. Biotechnol. Bioeng. 2016;113: 2286-2297. © 2016 Wiley Periodicals, Inc.
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Metastasis is a dynamic process involving the dissemination of circulating tumor cells (CTCs) through blood flow to distant tissues within the body. Nevertheless, the development of an in vitro platform that dissects the crucial steps of... more
Metastasis is a dynamic process involving the dissemination of circulating tumor cells (CTCs) through blood flow to distant tissues within the body. Nevertheless, the development of an in vitro platform that dissects the crucial steps of metastatic cascade still remains a challenge. We here developed an in vitro model of extravasation composed of (i) a single channel-based 3D cell laden hydrogel representative of the metastatic site, (ii) a circulation system recapitulating the bloodstream where CTCs can flow. Two polymers (i.e., fibrin and alginate) were tested and compared in terms of mechanical and biochemical proprieties. Computational fluid-dynamic (CFD) simulations were also performed to predict the fluid dynamics within the polymeric matrix and, consequently, the optimal culture conditions. Next, once the platform was validated through perfusion tests by fluidically connecting the hydrogels with the external circuit, highly metastatic breast cancer cells (MDA-MB-231) were inj...