The synergistic effect of aligned nanofibers and hyaluronic acid modification on endothelial cell behavior for vascular tissue engineering

The endothelialization of tissue-engineered vascular grafts (TEVGs) is considered to be an effective strategy to prevent the coagulation and restenosis of small-diameter vascular grafts. In this study, we fabricated well aligned nanofibrous scaffolds with PCL using a high speed rotating collector, modified those surfaces with hyaluronic acid (HA) and studied the synergistic effect of the scaffolds on the endothelial cells behavior in vitro. The well-aligned oriented architecture was observed by SEM images in the nanofibrous scaffolds. The contact angle measurements and FTIR-ATR evidenced that HA was successfully modified on the PCL nanofibrous scaffolds and hydrophilicity of the scaffolds was increased after HA coating. The results of adhesion and morphology of human umbilical vein endothelial cells (HUVECs) showed that the HA-coating aligned PCL (HA-aPCL) nanofibrous scaffolds could highly promote attachment and guide HUVECs bipolar spread with the parallel aligned nanofibers. Furthermore, HUVECs on the HA-aPCL formed a confluent monoendothelial cell layer and exhibited superior protein expression levels of von Willebrand factor (vWF). This study suggested that the combination of aligned nanostructure and HA modification was more capable of promoting the regeneration of functional endothelium for vascular tissue engineering than individual use.     

In vitro study in the endothelial cell compatibility and endothelialization of genipin-crosslinked biological tissues for tissue-engineered vascular scaffolds

To overcome the cytotoxicity of the chemical reagents used to fix bioprostheses, genipin, a naturally occurring crosslinking agent, was used to fix biological tissues in present study. We prepared the biological vascular scaffolds through cell extraction and fixing the porcine thoracic arteries with 1% (by w/v) genipin solution for 3 days, and then examined their mechanical properties and microstructures; glutaraldehyde- and epoxy-fixed counterparts were used as controls. HUVECs were seeded on the type I collagen-coated surface of different modified acellular vascular tissues (fixed with different crosslinking agents), and the growths of HUVECs on the specimens were demonstrated by means of MTT test, the secretion of PGI₂ and vWF by HUVECs on the various specimens was also measured. Finally, HUVECs were seeded on the luminal surface of acellular biological vascular scaffolds (<6 mm internal diameter) which were, respectively, treated in the same manner described above, and then cultured for 9 days. On the ninth day, the HUVECs on the luminal surface of these vascular scaffolds were examined morphologically and by immunohistochemistry. Genipin-fixation can markedly diminish antigenicity of the vascular tissues through partially getting rid of cell or reducing the level of free amino groups in the vascular tissues. Genipin-fixed acellular vascular tissues mimicked the natural vessels due to the maintenance of the integrity of total structure and the large preservation of the microstructures of collagen fibers and elastic fibers; therefore, it appeared suitable to fabricate vascular scaffolds in mechanical properties. Compared to controls, the genipin-fixed acellular vascular tissues were characterized by low cytotoxicity and good cytocompatibility. The HUVECs can not only proliferate well on the genipin-fixed acellular vascular tissues, but also preserve the activities and function of endothelial cells, and easily make it endothelialized in vitro. The results showed that the genipin-fixed acellular porcine vascular scaffolds should be promising materials for fabricating vascular grafts or the scaffolds of tissue-engineered blood vessels.     

Heparin-modified small-diameter nanofibrous vascular grafts

Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter vascular grafts. Here we produced 1-mm diameter vascular grafts with nanofibrous structure via electrospinning, and successfully modified the nanofibers by the conjugation of heparin using di-amino-poly(ethylene glycol) (PEG) as a linker. Antithrombogenic activity of these heparin-modified scaffolds was confirmed in vitro. After 1 month implantation using a rat common carotid artery bypass model, heparin-modified grafts exhibited 85.7% patency, versus 57.1% patency of PEGylated grafts and 42.9% patency of untreated grafts. Post-explant analysis of patent grafts showed complete endothelialization of the lumen and neovascularization around the graft. Smooth muscle cells were found in the surrounding neo-tissue. In addition, greater cell infiltration was observed in heparin-modified grafts. These findings suggest heparin modification may play multiple roles in the function and remodeling of nanofibrous vascular grafts, by preventing thrombosis and maintaining patency, and by promoting cell infiltration into the three-dimensional nanofibrous structure for remodeling.     

Elastin and collagen enhances electrospun aligned polyurethane as scaffolds for vascular graft

Mismatch in mechanical properties between synthetic vascular graft and arteries contribute to graft failure. The viscoelastic properties of arteries are conferred by elastin and collagen. In this study, the mechanical properties and cellular interactions of aligned nanofibrous polyurethane (PU) scaffolds blended with elastin, collagen or a mixture of both proteins were examined. Elastin softened PU to a peak stress and strain of 7.86 MPa and 112.28 % respectively, which are similar to those observed in blood vessels. Collagen-blended PU increased in peak stress to 28.14 MPa. The growth of smooth muscle cells (SMCs) on both collagen-blended and elastin/collagen-blended scaffold increased by 283 and 224 % respectively when compared to PU. Smooth muscle myosin staining indicated that the cells are contractile SMCs which are favored in vascular tissue engineering. Elastin and collagen are beneficial for creating compliant synthetic vascular grafts as elastin provided the necessary viscoelastic properties while collagen enhanced the cellular interactions.     

Functionalization of the surface of electrospun poly(epsilon-caprolactone) mats using zwitterionic poly(carboxybetaine methacrylate) and cell-specific peptide for endothelial progenitor cells capture

A novel approach for vascular grafts to achieve rapid endothelialization is to attract endothelial progenitor cells (EPCs) from peripheral blood onto grafts via EPC-specific antibodies, aptamer, or peptides that specifically bind to EPCs. Inspired by this idea, the electrospun poly(epsilon-caprolactone) (PCL) mats were modified with zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and phage display-selected-EPC-specific peptide, TPSLEQRTVYAK (TPS). We tested the physical and chemical properties, cyto-compatibility, and platelet adhesion of the modified material, and investigated the specificity of the functionalized surface for capturing EPCs. The results indicated that PCL modified with zwitterionic PCBMA and TPS peptide showed improved hydrophilicity without morphology change and damage of the mats. Furthermore, the modified material supported adherence and growth of vascular cells and resisted platelets adhesion. The surfaces also specifically captured EPCs rather than bone marrow mesenchymal stem cells and human umbilical vein endothelial cells. This surface-functionalized PCL graft may offer new opportunities for designing new vascular grafts.     

Co-electrospun blends of PU and PEG as potential biocompatible scaffolds for small-diameter vascular tissue engineering

A small-diameter vascular graft (inner diameter 4 mm) was fabricated from polyurethane (PU) and poly(ethylene glycol) (PEG) solutions by blend electrospinning technology. The fiber diameter decreased from 1023 ± 185 nm to 394 ± 106 nm with the increasing content of PEG in electrospinning solutions. The hybrid PU/PEG scaffolds showed randomly nanofibrous morphology, high porosity and well-interconnected porous structure. The hydrophilicity of these scaffolds had been improved significantly with the increasing contents of PEG. The mechanical properties of electrospun hybrid PU/PEG scaffolds were obviously different from that of PU scaffold, which was caused by plasticizing or hardening effect imparted by PEG composition. Under hydrated state, the hybrid PU/PEG scaffolds demonstrated low mechanical performance due to the hydrophilic property of materials. Compared with dry PU/PEG scaffolds with the same content of PEG, the tensile strength and elastic modulus of hydrated PU/PEG scaffolds decreased significantly, while the elongation at break increased. The hybrid PU/PEG scaffolds demonstrated a lower possibility of thrombi formation than blank PU scaffold in platelet adhesion test. The hemolysis assay illustrated that all scaffolds could act as blood contacting materials. To investigate further in vitro cytocompatibility, HUVECs were seeded on the scaffolds and cultured over 14 days. The cells could attach and proliferate well on the hybrid scaffolds than blank PU scaffold, and form a cell monolayer fully covering on the PU/PEG (80/20) hybrid scaffold surface. The results demonstrated that the electrospun hybrid PU/PEG tubular scaffolds possessed the special capacity with excellent hemocompatibility while simultaneously supporting extensive endothelialization with the 20 and 30% content of PEG in hybrid scaffolds.     

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold's microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications.     

Dual-acting biofunctionalised scaffolds for applications in regenerative medicine

Off the shelf scaffolds for replacing ultra-small diameter vascular grafts are valuable for reconstruction of diseased or damaged vessels. The limitations for such grafts include optimal handling with ready availability of varied lengths of grafts, graft patency with the ability to replace the function of active cellular mechanisms and adequate mechanical properties to maintain physicochemical function. We used a well-established, solvent casting method for potential tissue replacement scaffold fabrication with incorporated bioactive molecules, which we have previously explored to confer haemocompatibility. These grafts were tested in-vivo within the abdominal aorta of 10 Wistar rats and the patency was clinically and echographically evaluated. Haemocompatibility and endothelialisation were assessed on explants. Biofunctionalised scaffolds were also grafted subcutaneously and intraperitoneally to evaluate integration, inflammation and angiogenesis reactions. The potential wider applications of this dual acting scaffold were evaluated for its interactions with human dermal fibroblasts as well as bronchial epithelial cells. Physicochemical property evaluation of the functionalised grafts has clarified the mechanical strength and permeability. This study confirmed the microsurgical suturability of tubular grafts and graft patency of functionalized scaffolds. The study demonstrated the potential of a dual acting biofunctionalised scaffold’s use for a wide range of tissue engineering applications where micro-porous, yet impermeable scaffolds are needed.     

Biodegradable polyurethane composite scaffolds containing Bioglass® for bone tissue engineering

Five types of solid and porous polyurethane composites containing 5–20 wt.% of Bioglass® inclusions were synthesized. Porous structures were fabricated by polymer coagulation combined with the salt-particle leaching method. In-vitro bioactivity tests in simulated body fluid (SBF) were carried out and the marker of bioactivity, e.g. formation of surface hydroxyapatite or calcium phosphate layers upon immersion in SBF, was investigated. The chemical and physical properties of the solid and porous composites before and after immersion in SBF were evaluated using different techniques: Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA) and Thermogravimetric Analysis (TGA). Moreover the surface structure and microstructure of the composites was characterised by Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM), respectively. Mercury intrusion porosimetry, SEM and microtomography (μCT) were used to determine pore size distribution and porosity. The fabricated foams exhibited porosity >70% with open pores of 100–400 μm in size and pore walls containing numerous micropores of <10 μm. This pore structure satisfies the requirements for bone tissue engineering applications. The effects of Bioglass® addition on microstructure, mechanical properties and bioactivity of polyurethane scaffolds were evaluated. It was found that composite foams showed a higher storage modulus than neat polyurethane foams. The high bioactivity of composite scaffolds was confirmed by the rapid formation of hydroxyapatite on the foam surfaces upon immersion in SBF.     

Surface modified electrospun nanofibrous scaffolds for nerve tissue engineering

The development of biodegradable polymeric scaffolds with surface properties that dominate interactions between the material and biological environment is of great interest in biomedical applications. In this regard, poly-ε-caprolactone (PCL) nanofibrous scaffolds were fabricated by an electrospinning process and surface modified by a simple plasma treatment process for enhancing the Schwann cell adhesion, proliferation and interactions with nanofibers necessary for nerve tissue formation. The hydrophilicity of surface modified PCL nanofibrous scaffolds (p-PCL) was evaluated by contact angle and x-ray photoelectron spectroscopy studies. Naturally derived polymers such as collagen are frequently used for the fabrication of biocomposite PCL/collagen scaffolds, though the feasibility of procuring large amounts of natural materials for clinical applications remains a concern, along with their cost and mechanical stability. The proliferation of Schwann cells on p-PCL nanofibrous scaffolds showed a 17% increase in cell proliferation compared to those on PCL/collagen nanofibrous scaffolds after 8 days of cell culture. Schwann cells were found to attach and proliferate on surface modified PCL nanofibrous scaffolds expressing bipolar elongations, retaining their normal morphology. The results of our study showed that plasma treated PCL nanofibrous scaffolds are a cost-effective material compared to PCL/collagen scaffolds, and can potentially serve as an ideal tissue engineered scaffold, especially for peripheral nerve regeneration.     

Porous scaffold design for tissue engineering

A paradigm shift is taking place in medicine from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous material scaffolds integrated with biological cells or molecules to regenerate tissues. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and tissue regeneration. Little is known quantitatively about this balance as early scaffolds were not fabricated with precise porous architecture. Recent advances in both computational topology design (CTD) and solid free-form fabrication (SFF) have made it possible to create scaffolds with controlled architecture. This paper reviews the integration of CTD with SFF to build designer tissue-engineering scaffolds. It also details the mechanical properties and tissue regeneration achieved using designer scaffolds. Finally, future directions are suggested for using designer scaffolds with in vivo experimentation to optimize tissue-engineering treatments, and coupling designer scaffolds with cell printing to create designer material/biofactor hybrids.     

Experimental validation of a new approach for the development of mechano-compatible composite scaffolds for vascular tissue engineering

The clinical need for the design of small-diameter vascular substitutes with high patency rates has never been so urgent as nowadays. Mechano-compatibility is widely known as one of the main key parameter for the design and the development of highly-patent vascular substitutes independently of their nature, i.e., arterial prostheses, arterial grafts or tissue-engineered blood-vessel. In this work, we attempt to target mechano-compatibility of cylindrical scaffolds for vascular tissue engineering by a computational model based on the composite theory associated with finite element and genetic algorithm. Then, cylindrical composite scaffolds were fabricated from gelatine (matrix) and silk (reinforcement) to experimentally validate theoretical results obtained by the implemented computational model. Finally, the compliance of the scaffolds was measured by an in-house developed specific device. Results show that the computational predictions from numerical simulation are in good agreement with the measurements obtained form the experimental tests. Therefore, the proposed computational model represents a valid tool to assist biomaterial scientists during the design of composite scaffolds, and especially in targeting their mechanical properties.     

Fabrication of PU/PEGMA crosslinked hybrid scaffolds by in situ UV photopolymerization favoring human endothelial cells growth for vascular tissue engineering

Poly(ethylene glycol) methacrylate (PEGMA) was introduced into a polyurethane (PU) solution in order to prepare electrospun scaffold with improving the biocompatibility by electrospinning technology for potential application as small diameter vascular scaffolds. Crosslinked electrospun PU/PEGMA hybrid nanofibers were fabricated by a reactive electrospinning process with N,N'-methylenebisacrylamide as crosslinker and benzophenone as photoinitiator. The photoinduced polymerization and crosslinking reaction took place simultaneously during the electrospinning process. The electrospinning solutions with various weight ratios of PU/PEGMA were successfully electrospun. No significant difference in the scaffold morphology was found by SEM when PEGMA content was <20 wt%. The crosslinked fibrous scaffolds of PU/PEGMA exhibited higher mechanical strength than the pure PU scaffold. The hydrophilicity of scaffolds was controlled by varying the PU/PEGMA weight ratio. The tissue compatibility of electrospun nanofibrous scaffolds were tested using human umbilical vein endothelial cells (HUVECs). Cell morphology and cell proliferation were measured by SEM, fluorescence microscopy and thiazolyl blue assay (MTT) after 1, 3, 7 days of culture. The results indicated that the cell morphology and proliferation on the crosslinked PU/PEGMA scaffolds were better than that on the pure PU scaffold. Furthermore, the appropriate hydrophilic surface with water contact angle in the range of 55-75° was favorable of improvement the HUVECs adhesion and proliferation. Cells seeded on the crosslinked PU/PEGMA (80/20) scaffolds infiltrated into the scaffolds after 7 days of growth. These results indicated the crosslinked electrospun PU/PEGMA nanofibrous scaffolds were potential substitutes for artificial vascular scaffolds.     

Biostable highly aligned polyurethane fibres for the potential application of small calibre vascular grafting

Synthetic vascular grafting is necessarily when the autografting is not possible in some cases. Conventional polyethylene terephthalate and expanded polytetrafluoroethylene vascular grafts are found to be effective for diameter bigger than 6 mm but not for the diameter smaller than 4 mm due to the compliance mismatch and thrombogenicity. Endothelization on the surface of the graft can reduce the risks of compliance mismatch and thrombogenicity. In order to catalyst the endothelization process, fibrous morphology similar to the extracellular matrix of our body is preferable in the vascular grafts. Apart from that, the biostability of the grafts is also an essential element to be considered as the biodegradation may reduce the efficiency of the grafts. Many polyurethanes have been recognised as biostable materials. Hence, in this study, highly aligned polyurethane fibres are fabricated using a facile dry spinning technique in the view of providing effective sites for endothelization process to occur. These fibres are immersed into the simulated body fluid for as long as 24 weeks before conducting the biostability characterisations. The biostability is assessed in three aspects, physical, mechanical and chemical properties. Results show that the fibres do not have observable or significant deteriorations in all the three aspects mentioned.     

Surface-modified hyaluronic acid hydrogels to capture endothelial progenitor cells

A major challenge to the effective treatment of injured cardiovascular tissues is the promotion of endothelialization of damaged tissues and implanted devices. For this reason, there is a need for new biomaterials that promote endothelialization to enhance vascular repair. The goal of this work was to develop antibody-modified polysaccharide-based hydrogels that could selectively capture endothelial progenitor cells (EPCs). We showed that CD34 antibody immobilization on hyaluronic acid (HA) hydrogels provides a suitable surface to capture EPCs. The effect of CD34 antibody immobilization on EPC adhesion was found to be dependent on antibody concentration. The highest level of EPC attachment was found to be 52.2 cells per mm(2) on 1% HA gels modified with 25 μg mL(-1) antibody concentration. Macrophages did not exhibit significant attachment on these modified hydrogel surfaces compared to the EPCs, demonstrating the selectivity of the system. Hydrogels containing only HA, with or without immobilized CD34, did not allow for spreading of EPCs 48 h after cell seeding, even though the cells were adhered to the hydrogel surface. To promote spreading of EPCs, 2% (w/v) gelatin methacrylate (GelMA) containing HA hydrogels were synthesized and shown to improve cell spreading and elongation. This strategy could potentially be useful to enhance the biocompatibility of implants such as artificial heart valves or in other tissue engineering applications where formation of vascular structures is required.     

Biodegradable polycaprolactone scaffold with controlled porosity obtained by modified particle-leaching technique

Scaffold with controlled porosity constitute a cornerstone in tissue engineering, as a physical support for cell adhesion and growth. In this work, scaffolds of polycaprolactone were synthesized by a modified particle leaching method in order to control porosity and pore interconnectivity; the aim is to observe their influence on the mechanical properties and, in the future, on cell adhesion and proliferation rates. Low molecular weight PEMA beads with an average size of 200 μm were sintered with various compression rates in order to obtain the templates (negatives of the scaffolds). Then the melt polycaprolactone was injected into the porous template under nitrogen pressure in a custom made device. After cooling and solidifying of the melt polymer, the porogen was removed by selective dissolution in ethanol. The porosity and morphology of the scaffold were studied as well as the mechanical properties. Porosities from 60% to 85% were reached; it was found that pore interconnectivity logically increases with increasing porosity, and that mechanical strength decreases with increasing porosity. Because of their interesting properties and interconnected structure, these scaffolds are expected to find useful applications as a cartilage or bone repair material.     

Electrospun composite nanofibers for tissue regeneration

Nanotechnology assists in the development of biocomposite nanofibrous scaffolds that can react positively to changes in the immediate cellular environment and stimulate specific regenerative events at molecular level to generate healthy tissues. Recently, electrospinning has gained huge momentum with greater accessibility of fabrication of composite, controlled and oriented nanofibers with sufficient porosity required for effective tissue regeneration. Current developments include the fabrication of nanofibrous scaffolds which can provide chemical, mechanical and biological signals to respond to the environmental stimuli. These nanofibers are fabricated by simple coating, blending of polymers/bioactive molecules or by surface modification methods. For obtaining optimized surface functionality, with specially designed architectures for the nanofibers (multi-layered, core-shell, aligned), electrospinning process has been modified and simultaneous 'electrospin-electrospraying' process is one of the most lately introduced technique in this perspective. Properties such as porosity, biodegradation and mechanical properties of composite electrospun nanofibers along with their utilization for nerve, cardiac, bone, skin, vascular and cartilage tissue engineering are discussed in this review. In order to locally deliver electrical stimulus and provide a physical template for cell proliferations, and to gain an external control on the level and duration of stimulation, electrically conducting polymeric nanofibers are also fabricated by electrospinning. Electrospun polypyrrole (PPy) and polyaniline (PAN) based scaffolds are the most extensively studied composite substrates for nerve and cardiac tissue engineering with or without electrical stimulations, and are discussed here. However, the major focus of ongoing and future research in regenerative medicine is to effectively exploit the pluripotent potential of Mesenchymal Stem Cell (MSC) differentiation on composite nanofibrous scaffolds for repair of organs.     

Novel electrospun polyurethane/gelatin composite meshes for vascular grafts

Novel polymeric micro-nanostructure meshes as blood vessels substitute have been developed and investigated as a potential solution to the lack of functional synthetic small diameter vascular prosthesis. A commercial elastomeric polyurethane (Tecoflex^® EG-80A) and a natural biopolymer (gelatin) were successfully co-electrospun from different spinnerets on a rotating mandrel to obtain composite meshes benefiting from the mechanical characteristics of the polyurethane and the natural biopolymer cytocompatibility. Morphological analysis showed a uniform integration of micrometric (Tecoflex^®) and nanometric (gelatin) fibers. Exposure of the composite meshes to vapors of aqueous glutaraldehyde solution was carried out, to stabilize the gelatin fibers in an aqueous environment. Uniaxial tensile testing in wet conditions demonstrated that the analyzed Tecoflex^®–Gelatin specimens possessed higher extensibility and lower elastic modulus than conventional synthetic grafts, providing a closer matching to native vessels. Biological evaluation highlighted that, as compared with meshes spun from Tecoflex^® alone, the electrospun composite constructs enhanced endothelial cells adhesion and proliferation, both in terms of cell number and morphology. Results suggest that composite Tecoflex^®–Gelatin meshes could be promising alternatives to conventional vascular grafts, deserving of further studies on both their mechanical behaviour and smooth muscle cell compatibility.     

Prolongation of the degradation period and improvement of the angiogenesis of zein porous scaffolds in vivo

Zein porous scaffolds modified with fatty acids have shown great improvement in mechanical properties and good cell compatibility in vitro, indicating the potential application as a bone tissue engineering substitute. The present study was conducted to systematically investigate whether the addition of fatty acids affects the short-term (up to 12 weeks) and long-term (up to 1 year) behaviors of scaffolds in vivo, mainly focusing on changes in the degradation period and inflammatory responses. Throughout the implantation period, no abnormal signs occurred and zein porous scaffolds modified with oleic acid showed good tolerance in rabbits, characterized by the growth of relatively more blood vessels in the scaffolds and only a slight degree of fibrosis histology. Moreover, the degradation period was prolonged from 8 months to 1 year as compared to the control. These results affirmed further that zein could be used as a new kind of natural biomaterial suitable for bone tissue engineering.     

Small-diameter tissue engineered vascular graft made of electrospun PCL/lecithin blend

In this study, natural lecithin was incorporated into cholesterol-poly(ε-caprolactone) (Chol-PCL) by solution blending in order to modify the performance of the hydrophobic and bio-inert PCL. The fibrous Chol-PCL/lecithin membranes were fabricated by electrospinning, and the surface morphology and properties were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, static water contact angle, and mechanical tensile testing. The blood compatibility of the scaffolds was evaluated by in vitro hemolysis assay. The cytocompatibility of the scaffolds was investigated by cell adhesion and proliferation using bone-marrow mesenchymal stem cells (MSCs). Subcutaneous implantation was also performed to evaluate the in vivo inflammatory reaction. The tubular tissue-engineered vascular graft (TEVG) was further constructed by rolling cell sheet comprising fibrous membrane and MSCs. Furthermore, endothelial cells (ECs) were seeded onto the lumen of the graft with the aim to form vascular endothelium. The preliminary results indicate that electrospun Chol-PCL/lecithin scaffolds show improved hemocompatibility and cytocompatibility compared with neat Chol-PCL, and combining the Chol-PCL/lecithin fibrous scaffold with MSCs and ECs with well controlled distribution is a promising strategy for constructing TEVGs.