Vascular Tissue Engineering Applications Research Articles

Development of Electrospinning Setup for Vascular Tissue-Engineering Application with Thick-Hierarchical Fiber Alignment.

Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology wasinvestigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

Toward “Green” Vessels: Characterization of Microstructure, Mechanics, and Endothelial Cell Interaction on Three Macro‐Tubular Plants for Vascular Tissue Engineering Applications

AbstractVascular tissue engineering aims to create vessel models for in vitro research and develop vascular grafts for in vivo applications using tubular scaffolds. Natural scaffolds outperform synthetic ones due to their biocompatibility and natural microenvironment supporting cell growth. Given the importance of producing biocompatible tubular scaffolds through cost‐effective and uncomplicated processes, this study introduces nature‐derived tubular structures from three decellularized tubular plants (Water Spinach, Green Onion, and Water Horsetail) as novel alternatives. Microstructural characterization on the luminal surfaces of the plants reveals unique surface topography for each. Water Spinach is the most promising graft candidate in suturability tests besides presenting the highest elongation before rupture in tensile test. Assessment of human endothelial cells on the luminal surfaces of decellularized scaffolds shows higher expression of Ki‐67 protein and a consistent increase in cell number on water spinach and green onion scaffolds compared to tissue culture plate as a control. Focal adhesion‐related molecule Vinculin is expressed more than twice on all scaffolds compared to control, and confluent cell monolayers are formed on water spinach and green onion scaffolds, as confirmed by VE‐cadherin. This study proposes an innovative approach to use the natural structure of macro‐tubular plants for the preparation of vascular scaffolds.

Preparation and Characterization of Crimped PLA Fibers With Surface Porous Structure to Promote Cell Adhesion and Growth

ABSTRACTElectrospun fibrous scaffolds are widely used in vascular tissue engineering because they are able to mimic the organizational structure and biological function of a natural extracellular matrix. Improving the topological structure and mechanical properties of electrospun fibrous scaffolds is crucial for achieving good interaction between cells and materials. Herein, oriented polylactic acid (PLA) fibers with surface porous structure were prepared by electrospinning. The orientation degree of the surface porous structure (84.77° ± 5.61°) was highly consistent with the orientation degree of the fiber (83.66° ± 7.31°), which improved the porosity of the fiber and promoted the adhesion of human umbilical vein endothelial cells (HUVECs). Then, by heat treatment, oriented PLA fibers with a surface porous structure were formed into a crimped state, which mimics the crimped structure and nonlinear mechanical properties of the elastic fibers within the blood vessel wall. The crimped PLA fibers with surface porous structure significantly improved the aspect ratio of HUVECs and promoted HUVECs‐oriented growth, which shows certain potential applications in vascular tissue engineering.

Poly(Lactic-Co-Glycolic Acid) Microparticles for the Delivery of Model Drug Compounds for Applications in Vascular Tissue Engineering

Introduction: Localized delivery of angiogenesis-promoting factors such as small molecules, nucleic acids, peptides, and proteins to promote the repair and regeneration of damaged tissues remains a challenge in vascular tissue engineering. Current delivery methods such as direct administration of therapeutics can fail to maintain the necessary sustained release profile and often rely on supraphysiologic doses to achieve the desired therapeutic effect. By implementing a microparticle delivery system, localized delivery can be coupled with sustained and controlled release to mitigate the risks involved with the high dosages currently required from direct therapeutic administration. Methods: For this purpose, poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated via anti-solvent microencapsulation and the loading, release, and delivery of model angiogenic molecules, specifically a small molecule, nucleic acid, and protein, were assessed in vitro using microvascular fragments (MVFs). Results: The microencapsulation approach utilized enabled rapid spherical particle formation and encapsulation of model drugs of different sizes, all in one method. The addition of a fibrin scaffold, required for the culture of the MVFs, reduced the initial burst of model drugs observed in release profiles from PLGA alone. Lastly, in vitro studies using MVFs demonstrated that higher concentrations of microparticles led to greater co-localization of the model therapeutic (miRNA) with MVFs, which is vital for targeted delivery methods. It was also found that the biodistribution of miRNA using the delivered microparticle system was enhanced compared to direct administration. Conclusion: Overall, PLGA microparticles, formulated and loaded with model therapeutic compounds in one step, resulted in improved biodistribution in a model of the vasculature leading to a future in translational revascularization.

Redefining vascular repair: revealing cellular responses on PEUU-gelatin electrospun vascular grafts for endothelialization and immune responses on in vitro models.

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0cm and a length of 11cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

Phototuning of Hyaluronic-Acid-Based Hydrogel Properties to Control Network Formation in Human Vascular Endothelial Cells.

In vitro network formation by endothelial cells serves as a fundamental model for studies aimed at understanding angiogenesis. The morphogenesis of these cells to form a network is intricately regulated by the mechanical and biochemical properties of the extracellular matrix. Here the effects of modulating these properties in hydrogels derived from phenolated hyaluronic acid (HA-Ph) and phenolated gelatin (Gelatin-Ph) are presented. Visible-light irradiation in the presence of tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate and sodium persulfate induces the crosslinking of these polymers, thereby forming a hydrogel and degrading HA-Ph. Human vascular endothelial cells form networks on the hydrogel prepared by visible-light irradiation for 45min (42W cm-2 at 450nm) but not on the hydrogels prepared by irradiation for 15, 30, or 60min. The irradiation time-dependent degradation of HA-Ph and the changes in the mechanical stiffness of the hydrogels, coupled with the expressions of RhoA and β-actin genes and CD44 receptors in the cells, reveal that the network formation is synergistically influenced by the hydrogel stiffness and HA-Ph degradation. These findings highlight the potential of tailoring HA-based hydrogel properties to modulate human vascular endothelial cell responses, which is critical for advancing their application in vascular tissue engineering.

The Effect of Pore Length on The Mechanical Properties of Vascular Scaffold Due to Systolic Pressure

Tissue replacements are highly limited due to the lack of vascularized tissue in the engineered tissue. Thus, incorporating the vascular scaffold in any injured tissue or organ is critical in the tissue regeneration. As one of elastic tissue in human body, mechanical properties are vital in engineering a vascular scaffold. Besides, interconnected pores and scaffold porosity are among the main considerations in designing the scaffold for allowing the vascularization. Therefore, this study aims to simulate the mechanical properties of three-dimensional (3D) printed vascular scaffold by observing the deformation and elasticity after being applied with the maximum systolic pressure. Scaffolds with three different pore lengths were simulated for compression and tensile analysis by using Finite Element Analysis (FEA) based on polyethylene terephthalate (PET) material’s properties. The findings indicated that effective elastic modulus of the vascular scaffolds varied based on the pore length with shortest pore length gave the highest elasticity, whilst scaffold with the longest pore length gave lowest elasticity. Besides, stress value of compression and tensile analysis for all scaffolds were did not exceed the PET’s yield strength that indicated the designed scaffolds will have high potential for vascular tissue engineering applications.

Surface modification of aligned electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-based scaffold for binding with fibronectin or collagen in vascular tissue engineering

BackgroundVascular diseases are a leading cause of morbidity and mortality worldwide. The combination of the natural polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with essential extracellular matrix proteins such as fibronectin (FN) or collagen (COL) using various methods (coating, grafting and air plasma) to create small-diameter vascular grafts holds significant promise in the field of vascular tissue engineering. MethodsThe final data from this study indicated that after conjugation, the films maintained a smooth surface area and preserved morphology. Endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs) were employed to assess the cytotoxicity, biocompatibility, and proliferation potential of cell lines treated with the synthesized films. The FN-binding PHBV and COL-binding PHBV films exhibited remarkable cell biocompatibility and cell proliferation rates. Furthermore, the treated cells exhibited specific gene expressions, including VEGFR-2, vWF, CD31, CD34, and CD133. Additionally, at specified time points, the cell retention rate and anti-coagulation ability of EPCs and HUVECs cultured on various PHBV films were tested, yielding successful outcomes. Significant findingsThe results suggested that FN-binding PHBV films represent an ideal bio-based polymer for applications in vascular tissue engineering.

Versatile, elastomeric and degradable polyHIPEs of poly(glycerol sebacate)-methacrylate and their application in vascular graft tissue-engineering

Polymer scaffolds are an important enabling technology in tissue engineering. A wide range of manufacturing techniques have been developed to produce these scaffolds, including porogen leaching, phase separation, gas foaming, electrospinning and 3D printing. However, all of these techniques have limitations. Delivering suitable scaffold porosity, small feature sizes and macroscopic geometry remain challenging.Here, we present the development of a highly versatile scaffold fabrication method utilising emulsion templating to produce polymerised high internal phase emulsions (polyHIPEs) of the polymer poly(glycerol sebacate) methacrylate (PGS-M). PGS-M is biocompatible, degradable and highly elastic, with tunable mechanical properties. PGS-M was formulated into an emulsion using solvents and surfactants and then photocured into polyHIPE structures. The porosity, degradation behaviour, mechanical properties and biocompatibility of the PGS-M polyHIPEs was investigated.The versatility of the PGS-M polyHIPEs was demonstrated with the production of various complex tubular scaffold shapes, using injection moulding. These shapes were designed for applications in vascular graft tissue engineering and included straight tubes, bends, branches, functioning valves, and a representative aortic arch. The PGS-M polyHIPE scaffolds supported vascular smooth muscle cells (SMCs) in 3D cell culture in a bioreactor.

Laponite nanoclay-modified sacrificial composite ink for perfusable channel creation via embedded 3D printing

Vascularization is a major hurdle in developing in vitro thick tissue constructs. Fortunately, embedded sacrificial printing has emerged as a promising technology to fabricate perfusable channels. The objective of this study is to develop a Laponite nanoclay-modified polyvinyl alcohol (PVA) sacrificial composite ink that has improved printability, minimized interdiffusivity, and satisfactory post-printing removability during embedded printing of perfusable channels. With the addition of Laponite nanoclay, not only the printability of the PVA-Laponite nanoclay composite ink is significantly improved, but also the interdiffusion between the gelatin precursor solution and the PVA-Laponite nanoclay composite ink is largely mitigated. The diffusion of the gelatin precursor solution into the PVA-Laponite nanoclay composite ink is of great importance for printing controllable perfusable channels since the diffused gelatin may cross-link as the gelatin composite matrix does during and after printing, resulting in residual gelatin gel in the channel and altered channel dimensions. In particular, the PVA-2.0% Laponite nanoclay sacrificial ink shows good printability and minimized interdiffusivity while maintaining good post-printing removability, which can be a good sacrificial composite ink for thick perfusable tissue creations. The channel diameter reduction due to the gelatin solution diffusion can be satisfactorily predicted based on the unidirectional diffusion model. This study further demonstrates the feasibility of using the proposed sacrificial ink for vascular tissue engineering applications.

Development of a Silk Fibroin-Small Intestinal Submucosa Small-Diameter Vascular Graft with Sequential VEGF and TGF-β1 Inhibitor Delivery for In Situ Tissue Engineering.

Proper endothelialization and limited collagen deposition on the luminal surface after graft implantation plays a crucial role to prevent the occurrence of stenosis. To achieve these conditions, a biodegradable graft with adequate mechanical properties and the ability to sequentially deliver therapeutic agents isfabricated. In this study, a dual-release system is constructed through coaxial electrospinning by incorporating recombinant human vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) inhibitor into silk fibroin (SF) nanofibers to form a bioactive membrane. The functionalized SF membrane as the inner layer of the graft is characterized by the release profile, cell proliferation and protein expression. It presents excellent biocompatibility and biodegradation, facilitating cell attachment, proliferation, and infiltration. The core-shell structure enables rapid VEGF release within 10 days and sustained plasmid delivery for 21 days. A 2.0-mm-diameter vascular graft is fabricated by integrating the SF membrane with decellularized porcine small intestinal submucosa (SIS), aiming to facilitate the integration process under a stable extracellular matrix structure. The bioengineered graft is functionalized with the sequential administration of VEGF and TGF-β1, and with the reinforced and compatible mechanical properties, thereby offers an orchestrated solution for stenosis with potential for in situ vascular tissue engineering applications.

Magnetic and Biocompatible Polyurethane Nanofiber Biomaterial for Tissue Engineering.

Recruitment of endothelial cells to cardiovascular device surfaces could solve issues of thrombosis, neointimal hyperplasia, and restenosis. Since current targeting strategies are often nonspecific, new technologies to allow for site-specific cell localization and capture in vivo are needed. The development of cytocompatible superparamagnetic iron oxide nanoparticles has allowed for the use of magnetism for cell targeting. In this study, a magnetic polyurethane (PU)-2205 stainless steel (2205-SS) nanofibrous composite biomaterial was developed through analysis of composite sheets and application to stent-grafts. The PU nanofibers provide strength and elasticity while the 2205-SS microparticles provide ferromagnetic properties. Sheets were electrospun at mass ratios of 0-4:1 (2205-SS:PU) and stent-grafts with magnetic or nonmagnetic stents were coated at the optimal ratio of 2:1. These composite materials were characterized by microscopy, mechanical testing, a sessile drop test, magnetic field measurement, magnetic cell capture assays, and cytocompatibility after 14 days of culturing with endothelial cells. Results of this study show that an optimal ratio of 2:1 2205-SS:PU results in a hydrophobic material that balanced mechanical and magnetic properties and was cytocompatible up to 14 days. Significant cell capture required a thicker material of 0.5 mm thickness. Stent-grafts fabricated from a magnetic coating and a magnetic stent demonstrated uniform cell capture throughout the device surface. This novel biomaterial exhibits a combination of mechanical and magnetic properties that enables magnetic capture of cells and other therapeutic agents for vascular and other tissue engineering applications.

3D Printing of Extracellular Matrix-Based Multicomponent, All-Natural, Highly Elastic, and Functional Materials toward Vascular Tissue Engineering.

3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio-instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio-instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering. Herein, 3D printable and perfusable multicomponent hydrogel constructs with high elasticity, self-recovery properties, excellent hydrodynamic performance, and improved bioactivity are reported. The materials' design strategy integrates fast gelation kinetics of sodium alginate (Alg), in situ crosslinking of tyramine-modified hyaluronic acid (HAT), and temperature-dependent self-assembly and biological functions of decellularized aorta (dAECM). Using extrusion-based printing approach, the capability to print the multicomponent hydrogel bioinks with high precision into a well-defined vascular constructs able to withstand flow and repetitive cyclic compressive loading, is demonstrated. Both in vitro and pre-clinical models are used to show the pro-angiogenic and anti-inflammatory properties of the multicomponent vascular constructs. This study presents a strategy to create new bioink whose functional properties are greater than the sum of their components and with potential applications in vascular tissue engineering and regenerative medicine.

Synthesis and characterization of novel copper-doped modified bioactive glasses as advanced blood-contacting biomaterials

Bioactive glasses (BGs) are among the most popular biomaterial categories. Due to their biocompatibility, bioactivity, antimicrobial, and angiogenesis abilities, they are increasingly utilized in a variety of tissue-engineering applications. Despite the excellent properties of BGs, their use as blood-contact biomaterials has been restricted because of their influence on the activation of the coagulation cascade. In this study, a series of modified borate-based BGs (containing B2O3, MgO, K2O, Na2O, and different concentrations of CuO) were synthesized by a melting-derived method. The synthesized BGs exhibited anticoagulant properties thanks to removing blood-clotting elements including calcium, phosphate, and silica. The results indicated that all of the BGs were in a glassy phase and did not show any significant cytotoxicity. The modified BGs showed antibacterial properties against S. aureus and P. aeruginosa bacteria. The investigation of hemocompatibility also revealed that none of the groups caused red blood cell rupture or initiated the coagulation cascade. This research demonstrated that the incorporation of copper ions into the modified BGs could dramatically improve the endothelial cell proliferation, migration, vascular endothelial growth factor secretion, tube formation, and expression of angiogenesis-related genes (vascular endothelial growth factor , KDR, hypoxia-inducible factor-1α α, and endothelial nitric oxide), resulting in the promotion of angiogenesis properties. According to the findings, it is achievable to synthesize multifunctional BGs for use in blood-contact applications by combining increased angiogenesis, anticoagulant, and antibacterial properties suitable for vascular tissue engineering applications.

Angiogenesis driven extracellular matrix remodeling of 3D bioprinted vascular networks

Angiogenesis plays a pivotal role in development and tissue growth, as well as in pathological conditions such as cancer. Being able to understand the basic mechanisms involved in the vascularization of tissues and angiogenic network formation provides a window to advance the development of in vitro tissue models and enhance tissue engineering applications. In this study, we leveraged a novel microfluidic-based three dimensional (3D) bioprinting technology and alginate-collagen type I (AGC) bioink, to develop a 3D bioprinting strategy to enable the biofabrication of complex angiogenic networks within the 3D structure. These networks were comprised of simian vacuolating virus 40 (SV40) transformed adult rat brain endothelial cell (SV-ARBEC)-laden hydrogel rings. With mechanical properties relevant for vascular tissue engineering applications, these bioprinted constructs formed spontaneous vascular networks, reminiscent of anisotropic tissue-like structures, while retaining high cellular viability. The vascular network formation was accompanied by extracellular matrix (ECM) remodeling, confirming sequential SV-ARBEC mediated collagen type I fiber deposition and reorganization. Treatment with broad spectrum matrix metalloproteinase (MMP) inhibitor supressed SV-ARBEC angiogenic sprouting, highlighting requirements of ECM remodeling in angiogenic network formation. This novel 3D microfluidic bioprinting technology and biocompatible AGC hydrogel fiber rings supported robust SV-ARBEC angiogenesis and corresponding ECM remodeling, allowing us to present a strategy suitable to advancing applications in vascular research and supporting the further development of disease models, novel testing beds for drug discovery and tissue engineering applications.

Infrared nanospectroscopy depth-dependent study of modern materials: morpho-chemical analysis of polyurethane/fibroin binary meshes.

Infrared scattering-type scanning near-field optical microscopy (IR s-SNOM) and imaging is here exploited together with attenuated total reflection (ATR) IR imaging and scanning electron microscopy (SEM) to depict the chemical composition of fibers in hybrid electrospun meshes. The focus is on a recently developed bio-hybrid material for vascular tissue engineering applications, named Silkothane®, obtained in the form of nanofibrous matrices from the processing of a silk fibroin-polyurethane (SFPU) blend via electrospinning. Morphology and chemistry of single fibers, at both surface and subsurface level, have been successfully characterized with nanoscale resolution, taking advantage of the IR s-SNOM capability to portray the nanoscale depth profile of this modern material working at diverse harmonics of the signal. The applied methodology allowed to describe the superficial characteristics of the mesh up to a depth of about 100 nm, showing that SF and PU do not tend to co-aggregate to form hybrid fibers, at least at the length scale of hundreds of nanometers, and that subdomains other than the fibrillar ones can be present. More generally, in the present contribution, the depth profiling capabilities of IR s-SNOM, so far theoretically predicted and experimentally proven only on model systems, have been corroborated on a real material in its natural conditions with respect to production, opening the room for the exploitation of IR s-SNOM as valuable technique to support the production and the engineering of nanostructured materials by the precise understanding of their chemistry at the interface with the environment.

Engineering Vascular Bioreactor Systems to Closely Mimic Physiological Forces In Vitro.

In vitro models of the vasculature play an important role in biomedical discovery research, with diverse applications in vascular biology, drug discovery, and tissue engineering. These models aim to replicate the conditions of the human vasculature including physical geometry, employing appropriate vascular cells exposed to physiological forces. However, vessel biology is complex, with multiple relevant cell types, precise three-dimensional (3D) architectural arrangement, an array of biological cues and pressure, flow rate, and shear stress stimulation that are difficult to replicate outside of the body. Vessel bioreactors typically comprise core modules, common to most systems: a 3D tubular scaffold to support cells, media and nutrient exchange for cell viability, a pumping module, and sensor arrays for monitoring. In our comprehensive review of the literature, foundational elements such as maintenance of cell viability, nutrient exchange with flow, use of 3D scaffolds, and basic sensing capabilities are well established. However, most bioreactor systems fail to adequately replicate combinations of physiologically relevant stimuli-including pressure, shear stress, and flow rate-independently, as system input parameters. At the root of this deficiency is the field's reliance on simple pumping systems designed for other applications, making it necessary to add resistors and compliance chambers to even approach human vascular conditions. As vascular biology research rapidly progressed it became increasingly clear that combinations of physical forces strongly influence cell phenotype, gene expression, and in turn can be drivers of pathology. We highlight the need for renewed innovation in vascular bioreactor development with a focus on the importance of providing appropriate physiological forces in the same system. Impact statement In vitro systems modeling aspects of the human vasculature are increasingly important in tissue engineering and biomedical research. Current systems maintain basic cell viability and facilitate nutrient exchange but poorly replicate physiological forces, reliant on simplistic pumping systems. Our review highlights the need to more accurately mimic arterial pressure, flow rate, and shear stress in the same system. Innovation in this area would improve in vitro modeling of the vasculature, significantly impacting tissue engineering and vascular biology in this area.

Heparin-coated Poly(ethylene terephthalate)/Graphene Oxide Nanofibers Used for Vascular Tissue Engineering Application

Heparin-coated Poly(ethylene terephthalate)/Graphene Oxide Nanofibers Used for Vascular Tissue Engineering Application

Construction of enzyme-laden vascular scaffolds based on hyaluronic acid oligosaccharides-modified collagen nanofibers for antithrombosis and in-situ endothelialization of tissue-engineered blood vessels

The current use of synthetic grafts often yields low patency in the reconstruction of small-diameter blood vessels owing to the deposition of thrombi and imperfect coverage of the endothelium on the graft lumen. Therefore, the design of vascular scaffolds with antithrombotic performance and endothelialization is greatly required. Herein, we developed an enzyme-laden scaffold based on hyaluronic acid oligosaccharides-modified collagen nanofibers (labeled HA-COL) to improve the anti-platelet capacity and endothelialization of vascular grafts. In this study, HA-COL nanofibers not only encouraged the endothelialization of vascular scaffolds, but acted as an antiplatelet enzyme-laden platform. Apyrase (Apy) and 5’-nucleotidase (5’-NT) were covalently grafted onto the nanofibers, which in turn converted the platelet-sensitive substance: adenosine diphosphate (ADP) into adenosine monophosphate (AMP) and adenosine, thereby, improving the antithrombotic performance of the scaffolds. Notably, the catalytic end-product: adenosine would work in coordination with HA-COL to synergistically enhance the endothelialization of the vascular scaffolds. The results demonstrated that the enzyme-laden scaffolds maintained catalytic performance, reduced platelet adhesion and aggregation, and guaranteed higher patency after 1-month in situ transplantation. Moreover, these scaffolds showed optimal cytocompatibility, tissue compatibility, scaffold biodegradability and tissue regenerative capability during in vivo implantation. Overall, these engineered vascular scaffolds demonstrated their capacity for endothelialization and antithrombotic performance, suggesting their potential for small-diameter vascular tissue engineering applications. Statement of significanceConsidering the critical problems in small-diameter vascular reconstruction, the enzyme-laden vascular scaffolds were prepared for improving in-situ endothelialization and antithrombotic performances of artificial blood vessels. The electrospun HA-COL nanofibers were used as the main matrix materials, which provided favorable structural templates for the regeneration of vasculature and functioned as a platform for the loading of enzymes. The enzyme-laden scaffolds with the biomimetic cascading reaction would convert ADP into adenosine, thereby, decreasing the sensitivity of platelets and improving the antithrombotic performance of tissue-engineered blood vessels (TEBVs). The nanofibrous scaffolds exhibited optimal cytocompatibility, tissue compatibility and regenerative capability, working together with catalytic products of dual-enzyme reaction that would synergistically contribute to TEBVs endothelialization. This study provides a new method for the improvement of in-situ endothelialization of small-diameter TEBVs while qualified with antithrombotic performance.

Strategies for Regenerative Vascular Tissue Engineering.

Vascularization remains one of the key challenges in creating functional tissue-engineered constructs for therapeutic applications. This review aims to provide a developmental lens on the necessity of blood vessels in defining tissue function while exploring stem cells as a suitable source for vascular tissue engineering applications. The intersections of stem cell biology, material science, and engineering are explored as potential solutions for directing vascular assembly.