Surface Modification Of Scaffolds Research Articles

Bioactive microgel-coated electrospun membrane with cell-instructive interfaces and topology for abdominal wall defect repair.

Current mesh materials used for the clinical treatment of abdominal defects struggle to balance mechanical properties and bioactivity to support tissue remodeling. Therefore, a bioactive microgel-coated electrospinning membrane was designed with the superiority of cell-instructive topology in guiding cell behavior and function for abdominal wall defect reconstruction. The electrostatic spinning technique was employed to prepare a bioabsorbable PLCL fiber membrane with an effective mechanical support. Additionally, decellularized matrix (dECM)-derived bioactive microgels were further coated on the fiber membrane through co-precipitation with dopamine, which was expected to endow cell-instructive hydrophilic interfaces and topological morphologies for cell adhesion. Moreover, the introduction of the dECM into the microgel promoted the myogenic proliferation and differentiation of C2C12 cells. Subsequently, in vivo experiments using a rat abdominal wall defect model demonstrated that the bioactive microgel coating significantly contributed to the reconstruction of intact abdominal wall structures, highlighting its potential for clinical application in promoting the repair of soft tissue defects associated with abdominal wall damage. This study presented an effective mesh material for facilitating the reconstruction of abdominal wall defects and contributed novel design concepts for the surface modification of scaffolds with cell-instructive interfaces and topology.

RGD and rhBMP-7 immobilized on zirconia scaffold with interweaved human dental pulp stem cells for promoting bone regeneration

Biomimetic surface modification of scaffolds with osteoinductive molecules is a promising strategy for improving the bioactivity of scaffold and stimulating stem cell signals in bone tissue engineering. Zirconia (ZrO2) offers excellent mechanical properties and biocompatibility, but its bio-inert nature hinders its use in bone regeneration applications. Recombinant human bone morphogenetic protein 7 (rhBMP-7) and arginine-glycine-aspartate (RGD) peptide were investigated for their potential use as surface-modifying biomolecules on the ZrO2 scaffold. Our results showed that human dental pulp stem cells (hDPSCs) were induced to osteogenic differentiation by rhBMP-7 and RGD in a dose-dependent manner. Significantly enhanced alkaline phosphatase activity and up-regulated expression of osteogenic genes in hDPSCs were associated with rhBMP-7 and RGD grafting onto the ZrO2 scaffold. Western blot analysis revealed that rhBMP-7 and RGD grafting led to activation of the SMAD1/5, p38 MARK, and ERK signaling pathways during hDPSCs differentiation. After 4 and 8 weeks of transplantation, the hDPSCs-seeded ZrO2-RGD-BMP-7 scaffold facilitated osteogenic differentiation and enhanced in vivo bone formation in critical-sized calvarial bone defects. The results support the simultaneous use of rhBMP-7 and RGD as surface-modifying biomolecules and hDPSCs as a source of osteogenic stem cells in conjugation with ZrO2-based porous scaffold for bone tissue engineering.

Osteogenic Activity on NaOH-Etched Three-Dimensional-Printed Poly-ɛ-Caprolactone Scaffolds in Perfusion or Spinner Flask Bioreactor.

Bioreactor systems, for example, spinner flask and perfusion bioreactors, and cell-seeded three-dimensional (3D)-printed scaffolds are used in bone tissue engineering strategies to stimulate cells and produce bone tissue suitable for implantation into the patient. The construction of functional and clinically relevant bone graft using cell-seeded 3D-printed scaffolds within bioreactor systems is still a challenge. Bioreactor parameters, for example, fluid shear stress and nutrient transport, will crucially affect cell function on 3D-printed scaffolds. Therefore, fluid shear stress induced by spinner flask and perfusion bioreactors might differentially affect osteogenic responsiveness of pre-osteoblasts inside 3D-printed scaffolds. We designed and fabricated surface-modified 3D-printed poly-ɛ-caprolactone (PCL) scaffolds, as well as static, spinner flask, and perfusion bioreactors to determine fluid shear stress and osteogenic responsiveness of MC3T3-E1 pre-osteoblasts seeded on the scaffolds in the bioreactors using finite element (FE)-modeling and experiments. FE-modeling was used to quantify wall shear stress (WSS) distribution and magnitude inside 3D-printed PCL scaffolds within spinner flask and perfusion bioreactors. MC3T3-E1 pre-osteoblasts were seeded on NaOH surface-modified 3D-printed PCL scaffolds, and cultured in customized static, spinner flask, and perfusion bioreactors up to 7 days. The scaffolds' physicochemical properties and pre-osteoblast function were assessed experimentally. FE-modeling showed that spinner flask and perfusion bioreactors locally affected WSS distribution and magnitude inside the scaffolds. The WSS distribution was more homogeneous inside scaffolds in perfusion than in spinner flask bioreactors. The average WSS on scaffold-strand surfaces ranged from 0 to 6.5 mPa for spinner flask bioreactors, and from 0 to 4.1 mPa for perfusion bioreactors. Surface modification of scaffolds by NaOH resulted in a surface with a honeycomb-like pattern and increased surface roughness (1.6-fold), but decreased water contact angle (0.3-fold). Both spinner flask and perfusion bioreactors increased cell spreading, proliferation, and distribution throughout the scaffolds. Perfusion, but not spinner flask bioreactors more strongly enhanced collagen (2.2-fold) and calcium deposition (2.1-fold) throughout the scaffolds after 7 days compared with static bioreactors, likely due to uniform WSS-induced mechanical stimulation of the cells revealed by FE-modeling. In conclusion, our findings indicate the importance of using accurate FE models to estimate WSS and determine experimental conditions for designing cell-seeded 3D-printed scaffolds in bioreactor systems. Impact Statement The success of cell-seeded three-dimensional (3D)-printed scaffolds depends on cell stimulation by biomechanical/biochemical factors to produce bone tissue suitable for implantation into the patient. We designed and fabricated surface-modified 3D-printed poly-ɛ-caprolactone (PCL) scaffolds, as well as static, spinner flask, and perfusion bioreactors to determine wall shear stress (WSS) and osteogenic responsiveness of pre-osteoblasts seeded on the scaffolds using finite element (FE)-modeling and experiments. We found that cell-seeded 3D-printed PCL scaffolds within perfusion bioreactors more strongly enhanced osteogenic activity than within spinner flask bioreactors. Our results indicate the importance of using accurate FE-models to estimate WSS and determine experimental conditions for designing cell-seeded 3D-printed scaffolds in bioreactor systems.

Surface modifications of scaffolds for bone regeneration

An important strategy in bone tissue engineering is to design and implement biomaterials for the construction of desired scaffolds for the treatment of injuries or fractures. The scaffolds used in bone tissue engineering should have enough strength to withstand the mechanical stress during bone regeneration. However, synthetic or biological polymers used for the fabrication of bone scaffolds do not possess appropriate substrates for an effective material-cell interaction. Consequently, scaffolds are subjected to a variety of physical and chemical post-modifications, and this review discusses only various chemical methods used in post-modifications of scaffolds. Different chemical modifications of scaffolds surfaces are divided into three major categories including plasma surface modification, surface modification with various crosslinking agents and surface functionalization with different functional groups.

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

BackgroundThe poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.ResultsHerein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.ConclusionsOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical

Highly Ordered 3D Tissue Engineering Scaffolds as a Versatile Culture Platform for Nerve Cells Growth.

Tissue engineering scaffolds provide an encouraging alternative for nerve injuries due to their biological support for nerve cell growth, which can be used for neuronal repair. Nerve cells have been reported to be mostly cultured on 2D scaffolds that cannot mimic the native extracellular matrix. Herein, highly ordered 3D scaffolds are fabricated for nerve cell culture by melt electrospinning writing, the microstructures and geometries of the scaffolds could be well modulated. An effective strategy for scaffold surface modification to promote nerve cell growth is proposed. The effects of scaffolds with different surface modifications, viz., plasma treatment, single poly-D-lysine (PDL) coating after plasma treatment, single laminin (LM) coating after plasma treatment, double PDL and LM coatings after plasma treatment, on PC12 cell growth are evaluated. Experiments show the scaffold modified with double PDL and LM coatings after plasma treatment facilitated the growth of PC12 cells most effectively, indicating the synergistic effect of PDL and LM on the growth of nerve cells. This is the first systematic and quantitative study of the effects of different scaffold surface modifications on nerve cell growth. The above results provide a versatile culture platform for growing nerve cells, and for recovery from peripheral nerve injury.

Applications of Polydopamine-Modified Scaffolds in the Peripheral Nerve Tissue Engineering.

Peripheral nerve injury is a common and complicated traumatic disease in clinical neurosurgery. With the rapid advancement and development of medical technologies, novel tissue engineering provides alternative therapies such as nerve conduit transplantation. It has achieved significant outcomes. The scaffold surface modification is vital to the reconstruction of a pro-healing interface. Polydopamine has high chemical activity, adhesion, hydrophilicity, hygroscopicity, stability, biocompatibility, and other properties. It is often used in the surface modification of biomaterials, especially in the peripheral nerve regeneration. The present review discusses that polydopamine can promote the adhesion, proliferation, and differentiation of neural stem cells and the growth of neuronal processes. Polydopamine is widely used in the surface modification of nerve conduits and has a potential application prospect of repairing peripheral nerve injury. Polydopamine-modified scaffolds are promising in the peripheral nerve tissue engineering.

Design, fabrication, and optimization of a dual function three-layer scaffold for controlled release of metformin hydrochloride to alleviate fibrosis and accelerate wound healing

Abnormal wound healing caused by the over-expression of collagen and fibronectin leads to fibrosis, the major complication of all treatment modalities. A three-layer nanofiber scaffold was designed, optimized, and fabricated. This scaffold comprised two supportive polycaprolactone (PCL)-chitosan layers on the sides and a polyvinyl alcohol (PVA)-metformin hydrochloride (metformin-HCl) in the middle. The physico-chemical properties of scaffold, such as mechanical characteristics, degradation, swelling, and in-vitro drug release, were evaluated. The biological tests, including cell viability in response to metformin-HCl and Tween 80, scaffold biocompatibility, cell attachment, and antibacterial activity, were further conducted. The wound healing effect of scaffold loaded with metformin-HCl (MSc+Met) was assessed in donut-shaped silicone splints in rats. Histopathological and immunohistochemical evaluation as well as mRNA expression levels of fibrosis markers were also studied.SEM images indicated a uniform, bead-less morphology and high porosity. Surface modification of scaffold by Tween 80 improved the surface hydrophilicity and enhanced the adhesion and proliferation of fibroblasts. The scar area on day 15 in MSc+Met was significantly lower than that of other groups. Histopathological and immunohistochemical evaluation revealed that group MSc+Met was the best, having significantly lower inflammation, higher angiogenesis, the smallest scar width and depth, maximum epitheliogenesis score, and the most optimal modulation of collagen density. Local administration of metformin-HCl substantially down-regulated the expression of fibrosis-involved genes: transforming growth factor (TGF-β1), collagen type 1 (Col-I), fibronectin, collagen type 3 (Col-III), and alpha-smooth muscle actin (α-SMA). Inhibiting these genes alleviates scar formation but delays wound healing; thus, an engineered scaffold was used to prevent delay in wound healing. These results provided evidence for the first time to introduce an anti-fibrogenic slow-releasing scaffold, which acts in a dual role, both alleviating fibrosis and accelerating wound healing.

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells is enhanced by an aragonite scaffold

Bone graft substitutes and bone void fillers are predominantly used to treat bone defects and bone fusion in orthopaedic surgery. Some aragonite-based scaffolds of coralline exoskeleton origin exhibit osteoconductive properties and are described as useful bone repair scaffolds. The purpose of this study was to evaluate the in vitro osteogenic potential of the bone phase of a novel aragonite-based bi-phasic osteochondral scaffold (Agili-C™, CartiHeal Ltd.) using adult human bone marrow-derived mesenchymal stem cells (MSCs). Analyses were performed at several time intervals: 3, 7, 14, 21, 28 and 42 days post-seeding. Osteogenic differentiation was assessed by morphological characterisation using light microscopy after Alizarin red and von Kossa staining, and scanning electron microscopy. The transcript levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were determined by quantitative PCR. Proliferation was assessed by a thymidine incorporation assay and proliferating cell nuclear antigen (PCNA) immunocytochemistry. Our results demonstrate that the bone phase of the bi-phasic aragonite-based scaffold supports osteogenic differentiation and enhanced proliferation of bone marrow-derived MSCs at both the molecular and histological levels. The scaffold was colonized by differentiating MSCs, suggesting its suitability for incorporation into bone voids to accelerate bone healing, remodelling and regeneration. The mechanism of osteogenic differentiation involves scaffold surface modification with de novo production of calcium phosphate deposits, as revealed by energy dispersive spectroscopy (EDS) analyses. This novel coral-based scaffold may promote the rapid formation of high quality bone during the repair of osteochondral lesions.

Functionalization of Silk Fibroin Electrospun Scaffolds via BMSC Affinity Peptide Grafting through Oxidative Self-Polymerization of Dopamine for Bone Regeneration.

Electrospun scaffolds have been broadly studied to enhance bone regeneration because of the ability to simulate the structure and biological functions of the extracellular matrix. Polydopamine (PDA) is used to coat various surfaces at a slightly basic pH (8-8.5) and spontaneously reacts with nucleophilic functional groups. It is suitable for surface modifications of scaffolds correlated with bone formation. E7 is a newly discovered peptide with specific affinity for bone marrow mesenchymal stem cells (BMSCs). It can be useful for recruiting stem cells. Here, electrospun silk fibroin (SF) scaffolds were fabricated, and PDA was used for surface modification followed by grafting E7 (SF-PDA-E7). These composite SF-PDA-E7 electrospun scaffolds improved hydrophilicity, facilitated cell proliferation and adhesion, and boosted the osteogenic differentiation of BMSCs by creating osteoinduction conditions under the synergistic effects of PDA and E7. Moreover, the scaffolds showed high efficiency for recruiting BMSCs induced by E7 both in vitro and in vivo, which was associated with the SDF-1α/CXCR4 axis and the p38, extracellular signal-related kinase, and Akt signal transduction pathways. These functionalized electrospun scaffolds promoted regeneration of bone in the rat calvarial bone defect model. In general, this study verified that PDA could be a simple and efficient method for surface modification, and E7-grafted PDA-modified SF electrospun scaffolds were suitable for bone tissue engineering.

The deposition of thin titanium-nitrogen coatings on the surface of PCL-based scaffolds for vascular tissue engineering

Biodegradable polymer scaffolds for tissue engineering is a promising technology for therapies of patients suffering from the loss of tissue or its function including cardiac tissues. However, limitations such as hydrophobicity of polymers prevent cell attachment, cell conductivity, and endothelialization. Plasma modification of polymers allows producing materials for an impressive range of applications due to their unique properties. Here, we demonstrate the possibility of bioresorbable electrospun polycaprolacton (PCL) scaffold surface modification by reactive magnetron sputtering of the titanium target in a nitrogen atmosphere. The influence of the plasma treatment time on the structure and properties of electrospun PCL scaffolds was studied. We show that the plasma treatment does not change the physico-mechanical properties of electrospun PCL scaffolds, leads to an increase in PCL scaffold biocompatibility, and, simultaneously, increases their hydrophilicity. In conclusion, this modification method opens a route to producing scaffolds with enhanced biocompatibility for tissue engineered vascular grafts.

Time of flight secondary ion mass spectrometry-A method to evaluate plasma-modified three-dimensional scaffold chemistry.

Biopolymers are used extensively in the manufacture of porous scaffolds for a variety of biological applications. The surfaces of these scaffolds are often modified to encourage specific interactions such as surface modification of scaffolds to prevent fouling or to promote a cell supportive environment for tissue engineering implants. However, few techniques can effectively characterize the uniformity of surface modifications in a porous scaffold. By filling the scaffold pores through polymer embedding, followed by analysis with imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS), the distribution and composition of surface chemical species though complex porous scaffolds can be characterized. This method is demonstrated on poly(caprolactone) scaffolds modified with a low-fouling plasma-deposited coating from octafluoropropane via plasma enhanced chemical vapor deposition. A gradient distribution of CF+/CF3+ is observed for scaffolds plasma treated for 5 min, whereas a 20 min treatment results in more uniform distribution of the surface modification throughout the entire scaffold. The authors expect this approach to be widely applicable for ToF-SIMS analysis of scaffolds modified by multiple plasma processing techniques as well as alternative surface modification approaches.

Progress of Regenerative Therapy in Orthopedics.

To conduct a thorough appraisal of recent and inventive advances in the field of bone tissue engineering using biomaterials, cell-based research, along with the incorporation of biomimetic properties using surface modification of scaffolds. This paper will provide an overview on different biomaterials and emerging techniques involved in the fabrication of scaffolds, brief description of signaling pathways involved in osteogenesis, and the effect of surface modification on the fate of progenitor cells. The current strategies used for regenerative medicine like cell therapy, gene transfer, and tissue engineering have opened numerous therapeutic avenues for the treatment of various disabling orthopedic disorders. Precise strategy utilized for the reconstruction, restoration, or repair of the bone-related tissues exploits cells, biomaterials, morphogenetic signals, and appropriate mechanical environment to provide the basic constituents required for creating new tissue. Combining all the above strategies in clinical trials would pave the way for successful "bench to bedside" transformation in bone healing.

Effect of low-temperature plasma treatment of electrospun polycaprolactone fibrous scaffolds on calcium carbonate mineralisation.

This article reports on a study of the mineralisation behaviour of CaCO3 deposited on electrospun poly(ε-caprolactone) (PCL) scaffolds preliminarily treated with low-temperature plasma. This work was aimed at developing an approach that improves the wettability and permeability of PCL scaffolds in order to obtain a superior composite coated with highly porous CaCO3, which is a prerequisite for biomedical scaffolds used for drug delivery. Since PCL is a synthetic polymer that lacks functional groups, plasma processing of PCL scaffolds in O2, NH3, and Ar atmospheres enables introduction of highly reactive chemical groups, which influence the interaction between organic and inorganic phases and govern the nucleation, crystal growth, particle morphology, and phase composition of the CaCO3 coating. Our studies showed that the plasma treatment induced the formation of O- and N-containing polar functional groups on the scaffold surface, which caused an increase in the PCL surface hydrophilicity. Mineralisation of the PCL scaffolds was performed by inducing precipitation of CaCO3 particles on the surface of polymer fibres from a mixture of CaCl2- and Na2CO3-saturated solutions. The presence of highly porous vaterite and nonporous calcite crystal phases in the obtained coating was established. Our findings confirmed that preferential growth of the vaterite phase occurred in the O2-plasma-treated PCL scaffold and that the coating formed on this scaffold was smoother and more homogenous than those formed on the untreated PCL scaffold and the Ar- and NH3-plasma-treated PCL scaffolds. A more detailed three-dimensional assessment of the penetration depth of CaCO3 into the PCL scaffold was performed by high-resolution micro-computed tomography. The assessment revealed that O2-plasma treatment of the PCL scaffold caused CaCO3 to nucleate and precipitate much deeper inside the porous structure. From our findings, we conclude that O2-plasma treatment is preferable for PCL scaffold surface modification from the viewpoint of use of the PCL/CaCO3 composite as a drug delivery platform for tissue engineering.

ID: 1076 Establishing an artificial cartilage from rabbit bone marrow derived mesenchymal stem cell and polycaprolactone scaffold

Nowaday, the regenerative medicine based on the use of biomaterial scaffold combine to stem cells was considered as a necessary treatment strategy for injury or diseases involving cartilage. In this study, we investigated the adherence, proliferation and chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (rBM-MSCs) on biodegradable polycaprolactone scaffold (PCL). MSCs were isolated from bone marrow of rabbit. rBM-MSC (2x105cell/scaffold) were seeded on PCL and collagen-coated PCL (PCL/col) scaffolds. The cell adhesion and proliferation abilities on the PCL and PCL/col scaffolds were compared to each other to find the better using MTT assay. Then 3D cultured-cells were induced in chondrogenic differentiation medium. The change of scaffold surface structure was evaluated by scanning electron microscope (SEM). The accumulation of aggrecan protein was detected by Alcian Blue staining. The chondrogenic-related gene expression such as sox9, collagen type 1, collagen type 2, collagen type 10, aggrecan, runx2 was assessed by RT-PCR. The existence of artificial cartilage after transplantation of chondrocyte-seeded scaffold under rabbit skin was evaluated by staining histological sections with Alcian Blue. The results showed that rBM-MSCs attached and grown on PCL/col and PCL scaffolds. However, the adhesion efficient of rBM-MSC on PCL/col scaffold was better than PCL scaffolds. Therefore, PCL/col scaffold was used for next experiments. The morphology of rBM-MSCs on PLC/col scaffold were changed and the aggrecan accumulation increased after cultured in chondrogenic differentiation medium. The scaffold surface modification was detected with the presentation of collagen-like fiber structures. The expression of chondrogenesis-associated genes increased after 3, 7, 21, 28 days of chondrogenic induction, especially for collagen type II, collagen type I, aggrecan and collagen type X. Transplanted artificial cartilage was existed in rabbit for six weeks. The mature chondrocyte-like cells were detected and cartilage specific-proteoglycan accumulated more in differentiated cell-scaffold than scaffold seeded undifferentiated-cells. Thus artificial cartilage could be created when differentiating rBM-MSC into chondrocyte on collagen-coated PCL scaffold.

Spreading, proliferation and differentiation of human dental pulp stem cells on chitosan scaffolds immobilized with RGD or fibronectin.

Nowadays, human dental pulp stem cells (hDPSCs) became more attractive for therapeutic purposes because of their high proliferation and differentiation potential. Thus, coupling the desired cellular characteristics of hDPSCs with good biomaterial properties of the chitosan scaffolds provide an interesting approach for tissue engineering applications. On the other hand, scaffold surface modification is also needed to promote stem cell adhesion since chitosan lacks adhesion motifs to support direct cell anchorage. In this study, hDPSCs were isolated from third molars of healthy female individuals (aged 16-25) with enzymatic digestion. For cell culture studies, the chitosan scaffolds which have approximately 9mm diameter and 2mm thickness with interconnected structure were prepared by freeze-drying. To support cellular attachment the scaffolds were covalently immobilized with either RGD (arginine-glycine-aspartic acid) or fibronectin (Fn) molecules. Cells were seeded on chitosan scaffolds with or without immobilized RGD and fibronectin. Cell attachment, spreading, adhesion behaviors and proliferation capacity were examined by scanning electron microscopy, immunofluorescence staining and PrestoBlue® assays, respectively. In addition, differentiation potential of hDPSCs on Fn immobilized chitosan scaffolds was determined with real time reverse transcriptase polymerase chain reaction analysis. The results showed that chitosan scaffolds were not able to support stem cell attachment. hDPSCs on chitosan scaffolds formed spheroids more quickly and the size of spheroids were smaller than on chitosan-RGD while Fn-immobilized chitosan scaffolds strongly supported cellular attachment but not odontogenic differentiation. The results suggest that the Fn-immobilized chitosan scaffolds may serve as good three-dimensional substrates for dental pulp stem cell attachment and proliferation. In the case of dental regeneration, they must be supported by appropriate biosignals to induce odontogenic differentiation.

Hybrid 3D–2D printing for bone scaffolds fabrication

It is a well-known fact that bone scaffold topography on micro- and nanometer scale influences the cellular behavior. Nano-scale surface modification of scaffolds allows the modulation of biological activity for enhanced cell differentiation. To date, there has been only a limited success in printing scaffolds with micro- and nano-scale features exposed on the surface. To improve on the currently available imperfect technologies, in our paper we introduce new hybrid technologies based on a combination of 2D (nano imprint) and 3D printing methods. The first method is based on using light projection 3D printing and simultaneous 2D nanostructuring of each of the layers during the formation of the 3D structure. The second method is based on the sequential integration of preliminarily created 2D nanostructured films into a 3D printed structure. The capabilities of the developed hybrid technologies are demonstrated with the example of forming 3D bone scaffolds. The proposed technologies can be used to fabricate complex 3D micro- and nanostructured products for various fields.

Cell-based strategies for vascular regeneration.

Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ.

Structural properties of scaffolds: Crucial parameters towards stem cells differentiation.

Tissue engineering is a multidisciplinary field that applies the principles of engineering and life-sciences for regeneration of damaged tissues. Stem cells have attracted much interest in tissue engineering as a cell source due to their ability to proliferate in an undifferentiated state for prolonged time and capability of differentiating to different cell types after induction. Scaffolds play an important role in tissue engineering as a substrate that can mimic the native extracellular matrix and the properties of scaffolds have been shown to affect the cell behavior such as the cell attachment, proliferation and differentiation. Here, we focus on the recent reports that investigated the various aspects of scaffolds including the materials used for scaffold fabrication, surface modification of scaffolds, topography and mechanical properties of scaffolds towards stem cells differentiation effect. We will present a more detailed overview on the effect of mechanical properties of scaffolds on stem cells fate.

Surface modification by allylamine plasma polymerization promotes osteogenic differentiation of human adipose-derived stem cells.

Tuning the material properties in order to control the cellular behavior is an important issue in tissue engineering. It is now well-established that the surface chemistry can affect cell adhesion, proliferation, and differentiation. In this study, plasma polymerization, which is an appealing method for surface modification, was employed to generate surfaces with different chemical compositions. Allylamine (AAm), acrylic acid (AAc), 1,7-octadiene (OD), and ethanol (ET) were used as precursors for plasma polymerization in order to generate thin films rich in amine (-NH2), carboxyl (-COOH), methyl (-CH3), and hydroxyl (-OH) functional groups, respectively. The surface chemistry was characterized by X-ray photoelectron spectroscopy (XPS), the wettability was determined by measuring the water contact angles (WCA) and the surface topography was imaged by atomic force microscopy (AFM). The effects of surface chemical compositions on the behavior of human adipose-derive stem cells (hASCs) were evaluated in vitro: Cell Count Kit-8 (CCK-8) analysis for cell proliferation, F-actin staining for cell morphology, alkaline phosphatase (ALP) activity analysis, and Alizarin Red S staining for osteogenic differentiation. The results show that AAm-based plasma-polymerized coatings can promote the attachment, spreading, and, in turn, proliferation of hASCs, as well as promote the osteogenic differentiation of hASCs, suggesting that plasma polymerization is an appealing method for the surface modification of scaffolds used in bone tissue engineering.