Small-diameter Blood Vessels Research Articles

Bidirectional Elastic PTFE Small Diameter Artificial Blood Vessel Grafts and Surface Antithrombotic Functionalized Construction.

Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.

Optimization of mechanical properties of small diameter artificial blood vessels based on alginate/chitosan/gelatin

Due to the rise in cardiovascular disease and the problem of autologous transplant limitation, the emergence of 3D bioprinted blood vessels using natural polymer materials as ink is becoming increasingly important in the field of small-diameter artificial blood vessels (φ ≤ 6 mm). In this paper, gelatin was firstly adopted to explore alginate/chitosan composite hydrogel properties and solve the current issues of poor mechanical performance and suboptimal printability of small-diameter blood vessels, which indicated that the modification caused a 17.7 % increase in compressive strength and a 63.2 % enhancement in tensile properties. The material microstructure evaluation showed that the samples with gelatin(4 %) presented the excellent water absorption rate(>90 %) significantly increasing their porosities. A self-developed 3D bioprinter was utilized to clarify the controllable mechanism of small-diameter artificial blood vessel, which has superior performance and excellent printability. This study provides a new reference solution to the current challenges in the bio-ink performance and printability of small-diameter artificial blood vessels.

Stem‐Cell‐Based Small‐Diameter Blood Vessels with 3D Printing

Cardiovascular disease has emerged as the leading cause of death worldwide. Since coronary arteries, carotid arteries, and other blood vessels are prone to narrowing, small‐diameter artificial blood channels offer a crucial solution for restoring blood flow. Ideal grafts must emulate the structure of natural blood vessels, possess adequate mechanical strength, ensure long‐term patency, and incorporate functional cells with minimal immunogenicity. Enhanced cell sources and engineering methods are vital for the creation of functional small‐diameter blood vessels (SDBVs). Among potential cell sources, stem cells stand out due to their ability to differentiate into multiple cell types, self‐renew, and exhibit low immunogenicity. Additionally, three‐dimensionally (3D) printed vascular stents have attracted widespread attention for their precision and controllable bioink application. The need for tissue‐engineered blood vessels is currently rising, and innovative design concepts integrating stem cells and 3D printing present promising solutions. Herein, the construction requirements of vascular grafts are reviewed, current status of using stem cells as a cell source and 3D printing as an engineering strategy is described, and prospects and challenges for the development of SDBVs in the medical field are discussed.

Tailored endothelialization enabled by engineered endothelial cell vesicles accelerates remodeling of small-diameter vascular grafts

Current gold standard for the replacement of small-diameter blood vessel (ID < 4 mm) is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts (SDVG) on weak endothelialization, intimal hyperplasia and low patency. Herein, we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling. The engineered endothelial cell vesicles were modified with azide groups (ECVs-N3) through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry, and thus fabricating ECVG (ECVs-N3 modified SDVG), which assists inhibition of platelet adhesion and activation, promotion of ECs adhesion and enhancement of anti-inflammation. Furthermore, In vivo single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL, and the tailored endothelialization enabled to convert endothelial cells (ECs) into some specific ECs clusters. One of the specific cluster, Endo_C5 cluster, was only detected in ECVG. Consequently, our study integrates the engineered membrane vesicles of ECVs-N3 from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells, and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.

Engineered 3D-printed poly(vinyl alcohol) vascular grafts: Impact of thermal treatment and functionalization

Cardiovascular diseases, a leading cause of global mortality, are driving increased demand for artificial blood vessels for surgical repair. This study discloses the fabrication of three-dimensional (3D)-printed small blood vessels as tissue-engineered grafts. Large-diameter artery and vein grafts are readily available in the market, but small-diameter blood vessels face issues due to the lack of suitable materials. Lysine-biofunctionalized and unmodified poly(vinyl alcohol) grafts (PVA grafts) (2 mm inner diameter and 3 mm outer diameter) suitable for veins and venules were designed using Fusion 360 software, Autodesk Fusion. The PVA channels were fabricated from the 3D virtual model through fused deposition modeling using a PVA filament. These channels underwent thermal treatment to adjust their crystallinity, chemical crosslinking, and functionalization to optimize their mechanical properties and biocompatibility. Crosslinking and biofunctionalization were assessed using Fourier-transform infrared spectroscopy with attenuated total reflectance, while X-ray diffraction and differential scanning calorimetry were utilized for structural analysis. PVA grafts were biologically tested using three specific types of cell cultures: bEnd.3 brain endothelial cells, L929 fibroblast cells, and U937 monocyte-like cells. The hemocompatibility of the optimized vascular grafts was evaluated using horse blood, following the guidelines outlined in ASTM F756-13 Standard Practice for Assessment of Hemolytic Properties of Materials. The direct method for hemoglobin determination was specifically employed. Additionally, we developed an external polyethylene terephthalate glycol (PETG) 3D-printed platform to house the PVA grafts in parallel. The assembled platform (PETG and PVA graft) was connected to both an inlet and an outlet to facilitate the passage of an aqueous flow through the internal section of the PVA grafts during a flow test conducted under simulated body conditions (vacuum and blood pressure: 40 mbar). The flow was induced by a vacuum pump connected to the outlet of the platform, while the inlet was connected to a feeding glass. In summation, we have established a suitable protocol for producing small vascular grafts and demonstrated that the optimization process could significantly affect graft properties.

Vascular Damage and Repair - Are Small-Diameter Vascular Grafts Still the "Holy Grail" of Tissue Engineering?

Cardiovascular diseases are the most important cause of morbidity and mortality in the civilized world. Stenosis or occlusion of blood vessels leads not only to events that are directly life-threatening, such as myocardial infarction or stroke, but also to a significant reduction in quality of life, for example in lower limb ischemia as a consequence of metabolic diseases. The first synthetic polymeric vascular replacements were used clinically in the early 1950s. However, they proved to be suitable only for larger-diameter vessels, where the blood flow prevents the attachment of platelets, pro-inflammatory cells and smooth muscle cells on their inner surface, whereas in smaller-diameter grafts (6 mm or less), these phenomena lead to stenosis and failure of the graft. Moreover, these polymeric vascular replacements, like biological grafts (decellularized or devitalized), are cell-free, i.e. there are no reconstructed physiological layers of the blood vessel wall, i.e. an inner layer of endothelial cells to prevent thrombosis, a middle layer of smooth muscle cells to perform the contractile function, and an outer layer to provide innervation and vascularization of the vessel wall. Vascular substitutes with these cellular components can be constructed by tissue engineering methods. However, it has to be admitted that even about 70 years after the first polymeric vascular prostheses were implanted into human patients, there are still no functional small-diameter vascular grafts on the market. The damage to small-diameter blood vessels has to be addressed by endovascular approaches or by autologous vascular substitutes, which leads to some skepticism about the potential of tissue engineering. However, new possibilities of this approach lie in the use of modern technologies such as 3D bioprinting and/or electrospinning in combination with stem cells and pre-vascularization of tissue-engineered vascular grafts. In this endeavor, sex-related differences in the removal of degradable biomaterials by the cells and in the behavior of stem cells and pre-differentiated vascular cells need to be taken into account. Key words: Blood vessel prosthesis, Regenerative medicine, Stem cells, Footprint-free iPSCs, sr-RNA, Dynamic bioreactor, Sex-related differences.

Carnosine-copper chelator-modified small-diameter vascular grafts for the promotion of anticoagulation and endothelial regeneration

Thrombosis and poor endothelialization of small-diameter vascular grafts (SDVGs) remain the leading cause of frequent failure, despite current tissue-engineered vascular grafts providing a feasible strategy in clinical treatment strategies for the small-diameter (<6 mm) blood vessels in management of cardiovascular disease. Copper ions are normally used to achieve the purpose of antithrombotic because they can produce nitric oxide (NO) with the catalysis of NO donors. However, copper ions also participate in the Fenton reaction to produce reactive oxygen species (ROS), which would adversely affect vascular graft remodeling. Here carnosine, an ion-chelating agent with anti-inflammatory and antioxidant properties, was used to chelate with copper ions to synthesize carnosine-Cu (II) chelate which showed effective activity of antithrombotic, anti-inflammatory, and antioxidant. Besides, our research further demonstrated that copper ions still retain the catalytic activities for producing NO after chelating with carnosine accompanied by the production of lower levels of ROS (the average fluorescence intensity of ROS decreased from 79.69 to 7.13). Furthermore, the grafts achieved excellent patency with satisfactory endothelialization (the endothelial coverage reached 80.64 %) and significantly improved deposition of collagen and glycosaminoglycan for up to 12 weeks. In general, Car-Cu (II) modified SDVGs provided a facile approach to addressing the problems of thrombus and poor endothelialization in SDVGs for the clinic, which is significant in cardiovascular regenerative medicine.

Development and performance evaluation of a novel elastic bacterial nanocellulose/polyurethane small caliber artificial blood vessels

There is an increasing demand for small-diameter blood vessels. Currently, there is no clinically available small-diameter artificial vessel. Bacterial nanocellulose (BNC) has vast potential for applications in artificial blood vessels due to its good biocompatibility. At the same time, medical polyurethane (PU) is a highly elastic polymer material widely used in artificial blood vessels. This study reports a composite small-diameter BNC/PU conduit using a non-solvent-induced phase separation method with the highly hydrophilic BNC tube as the skeleton and the hydrophobic polycarbonate PU as the filling material. The results revealed that the compliance and mechanical matching of BNC/PU tubes were higher than BNC tubes; the axial/radial mechanical strength, burst pressure, and suture strength were significantly improved; the blood compatibility and cell compatibility were also excellent. The molecular and subcutaneous embedding tests showed that the composite tubes had lighter inflammatory reactions. The results of the animal substitution experiments showed that the BNC/PU tubes kept blood flow unobstructed without tissue proliferation after implantation in rats for 9 months. Thus, the BNC/PU small-diameter vascular prosthesis had the potential for long-term patency and acted as an ideal material for small-diameter vessels.

Fabrication of Vascular Grafts Using Poly(ε-Caprolactone) and Collagen-Encapsuled ADSCs for Interposition Implantation of Abdominal Aorta in Rhesus Monkeys.

The production of small-diameter artificial vascular grafts continues to encounter numerous challenges, with concerns regarding the degradation rate and endothelialization being particularly critical. In this study, porous PCL scaffolds were prepared, and PCL vascular grafts were fabricated by 3D bioprinting of collagen materials containing adipose-derived mesenchymal stem cells (ADSCs) on the internal wall of the porous PCL scaffold. The PCL vascular grafts were then implanted in the abdominal aorta of Rhesus monkeys for up to 640 days to analyze the degradation of the scaffolds and regeneration of the aorta. Changes in surface morphology, mechanical properties, crystallization property, and molecular weight of porous PCL revealed a similar degradation process of PCL in PBS at pH 7.4 containing Thermomyces lanuginosus lipase and in situ in the abdominal aorta of rhesus monkeys. The contrast of in vitro and in vivo degradation provided valuable reference data for predicting in vivo degradation based on in vitro enzymatic degradation of PCL for further optimization of PCL vascular graft fabrication. Histological analysis through hematoxylin and eosin (HE) staining and fluorescence immunostaining demonstrated that the PCL vascular grafts successfully induced vascular regeneration in the abdominal aorta over the 640-day period. These findings provided valuable insights into the regeneration processes of the implanted vascular grafts. Overall, this study highlights the significant potential of PCL vascular grafts for the regeneration of small-diameter blood vessels.

The Past, Present, and Future of Tubular Melt Electrowritten Constructs to Mimic Small Diameter Blood Vessels - A Stable Process?

Melt Electrowriting (MEW) is a continuously growing manufacturing platform. Its advantage is the consistent production of micro- to nanometer fibers, that stack intricately, forming complex geometrical shapes. MEW allows tuning of the mechanical properties of constructs via the geometry of deposited fibers. Due to this, MEW can create complex mechanicsonly seen in multi-material compounds and serve as guiding structures for cellular alignment. The advantage of MEW is also shown in combination with other biotechnological manufacturing methods to create multilayered constructs that increase mechanical approximation to native tissues, biocompatibility, and cellular response. These features make MEW constructs a perfect candidate for small-diameter vascular graft structures. Recently, studies have presented fascinating results in this regard, but is this truly the direction that tubular MEW will follow or are there also other options on the horizon? This perspective will explore the origins and developments of tubular MEW and present its growing importance in the field of artificial small-diameter vascular grafts with mechanical modulation and improved biomimicry and the impact of it in convergence with other manufacturing methods and how future technologies like AI may influence its progress.

Biomimetic approach to the design of artificial small‑diameter blood vessels

Objective: To create 2-mm diameter multilayer porous tubular scaffolds (PTS) with characteristics that resemble small-diameter native blood vessels in terms of characteristics.Materials and methods. PTS made of polycaprolactone (PCL, MM 80000) with a PCL-made sealing coat/layer with gelatin addition (PCL-gelatin) with a diameter of 2 mm were created by electrospinning (NANON-01A). Bioactive coating was applied to the PTS surface by sequential incubation in solutions of bovine serum albumin, heparin (Hp), and platelet lysate (PL). Cytotoxicity was investigated under conditions of direct contact of PTS with a monolayer of NIH/3T3 mouse fibroblasts. Viability of human umbilical vein endothelial cells (EA.hy926) was evaluated using Live/Dead® Viability/Cytotoxicity Kit. Permeability and blood flow parameters of the PTS implanted in the infrarenal section of the rat aorta were recorded using Doppler imaging.Results. A three-layer PTS construct with an inner diameter of 2 mm was developed. Its inner and outer layers were formed from 0.2 mL of PCL solution, and the middle sealing coat/layer was from 0.5 mL of PCL with addition of 30% (by weight of polymer) gelatin. Introduction of the sealing coat/layer reduced surgical porosity (SP) from 56.2 ± 8.7 mL/(cm2·min) for a single-layer PTS made of pure PCL to 8.9 ± 2.6 mL/(cm2·min) for a three-layer PTS. The resulting PTS demonstrated physicomechanical characteristics similar to those of native blood vessels; it also showed no cytotoxicity. Application of a bioactive coating of Hp and PL allowed for increased in vitro adhesion and proliferation of endothelial cells. The technique of implantation of 10 mm long fragments of three-layer PTS into the infrarenal section of a rat aorta was corrected, thus minimizing blood loss and narrowing the anastomosis site. In an acute experiment, it was proven that the prostheses were patent and that blood flow parameters (systolic and diastolic velocity, resistivity index) were close to the corresponding indicators of native rat aorta.Conclusion. The developed three-layer PTS constructs have low SP and physicomechanical properties close to those of native blood vessels. Bioactive coating improves the in vitro matrix properties of PTS relative to human endothelial cells. At short-term implantation into the aorta of experimental animals, PTS showed no early thrombosis, while blood flow parameters were close to those of native rat aorta. Thus, three-layer PTS with bioactive coating can be used as a scaffold for creation of in situ tissue-engineered construct of a small-diameter blood vessel.

MORPHOLOGICAL AND MECHANICAL ASSESSMENT OF ELECTROSPUN PLGA VASCULAR SCAFFOLDS

Cardiovascular disorders are the leading cause of global mortality and typically necessitate bypass surgery to replace the damaged blood vessel. Currently used grafts are insufficient to replace small-diameter blood vessels due to the scarcity and harsh harvesting procedure of autologous vessels and the shortcomings in the clinical performance of synthetic grafts, which might result in intimal hyperplasia, thrombosis, and compliance mismatch. Therefore, there is a critical need for tissue-engineered vascular grafts that can meet morphological, mechanical, and biological characteristics. In this study, poly(lactic-co-glycolic acid) tubular scaffolds with randomly distributed or radially oriented fibers were produced by electrospinning, and the effect of fiber orientation on morphological and mechanical properties was investigated. The findings demonstrate that, while the successful implementation of radial fiber orientation with high rotational speed production enhanced burst strength and radial tensile strength values, it was unfavorable for compliance.

Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small-Diameter Arteries.

The availability of grafts to replace small-diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue-engineered vascular graft that aims to match the natural structure of small-size arteries. The blood vessel mimic (BVM) comprises an internal conduit of co-electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding to the tunica intima of an artery), reinforced by an additional layer of PCL aligned fibers (the internal elastic membrane). Endothelial cells are deposited onto the luminal surface using a rotative bioreactor. A bioprinting system extrudes two concentric cell-laden hydrogel layers containing respectively vascular smooth muscle cells and pericytes to create the tunica media and adventitia. The semi-automated cellularization process reduces the production and maturation time to 6 days. After the evaluation of mechanical properties, cellular viability, hemocompatibility, and suturability, the BVM is successfully implanted in the left pulmonary artery of swine. Here, the BVM showed good hemostatic properties, capability to withstand blood pressure, and patency at 5 weeks post-implantation. These promising data open a new avenue to developing an artery-like product for reconstructing small-diameter blood vessels.

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts.

Tissue-engineered vascular grafts (TEVGs) have emerged as a potential alternative to autologous grafts for replacing small-diameter blood vessels during bypass surgery. The axial alignment of endothelial cells (ECs) and the circumferential alignment of smooth muscle cells (SMCs) are crucial for functional native blood vessels (NBVs). However, achieving this cellular alignment in TEVGs remains a formidable challenge. In this study, TEVGs were developed using a low-cost technique that aligned ECs axially and SMCs circumferentially within hours. The TEVGs comprised an electrospun polycaprolactone (PCL) layer and a gelatin methacryloyl (GelMA) cast layer. A freezing-induced alignment technique was developed that partially aligns the electrospun fibers axially, thereby promoting rapid axial alignment of ECs. Furthermore, SMCs cultured in a GelMA layer with intermediate stiffness (5-12 kPa) surrounding a PCL tube could promote conformation of the SMCs to the curvature of the PCL tube, resulting in their spontaneous circumferential alignment. Additionally, the TEVGs demonstrated mechanical properties similar to those of NBVs, which could facilitate future translation. This approach represents a significant advance in tissue engineering, enabling the fabrication of TEVGs with appropriate mechanical properties that recapitulate key NBV cell structural features within hours using a scalable and accessible method.

Porous Tubular Scaffolds for Tissue Engineering Structures of Small Diameter Blood Vessels

Porous Tubular Scaffolds for Tissue Engineering Structures of Small Diameter Blood Vessels

Poly(octamethylene citrate) Modified with Glutathione as a Promising Material for Vascular Tissue Engineering

One of the major goals of vascular tissue engineering is to develop much-needed materials that are suitable for use in small-diameter vascular grafts. Poly(1,8-octamethylene citrate) can be considered for manufacturing small blood vessel substitutes, as recent studies have demonstrated that this material is cytocompatible with adipose tissue-derived stem cells (ASCs) and favors their adhesion and viability. The work presented here is focused on modifying this polymer with glutathione (GSH) in order to provide it with antioxidant properties, which are believed to reduce oxidative stress in blood vessels. Cross-linked poly(1,8-octamethylene citrate) (cPOC) was therefore prepared by polycondensation of citric acid and 1,8-octanediol at a 2:3 molar ratio of the reagents, followed by in-bulk modification with 0.4, 0.8, 4 or 8 wt.% of GSH and curing at 80 °C for 10 days. The chemical structure of the obtained samples was examined by FTIR-ATR spectroscopy, which confirmed the presence of GSH in the modified cPOC. The addition of GSH increased the water drop contact angle of the material surface and lowered the surface free energy values. The cytocompatibility of the modified cPOC was evaluated in direct contact with vascular smooth-muscle cells (VSMCs) and ASCs. The cell number, the cell spreading area and the cell aspect ratio were measured. The antioxidant potential of GSH-modified cPOC was measured by a free radical scavenging assay. The results of our investigation indicate the potential of cPOC modified with 0.4 and 0.8 wt.% of GSH to produce small-diameter blood vessels, as the material was found to: (i) have antioxidant properties, (ii) support VSMC and ASC viability and growth and (iii) provide an environment suitable for the initiation of cell differentiation.

Transient deficiency of protein S after past infection process, complications and outcome: clinical case

Background. Purpura fulminans (PF) – is an acute rapidly progressive thrombosis of small-diameter blood vessels located mainly on the skin of the extremities. PF is characterized by high mortality rates. Patients can have serious consequences, including amputations and loss of fingers, foots or even extremities in general.Clinical case description. A clinical case of developing transient deficiency of protein S complicated by idiopathic PF on the 7th day after acute otitis in a 3-year-old boy due to past infection is presented. The progression of the disease developed within a few hours. The patient became hemorrhagic elements on the skin of extremities, and later — tissue necrosis. The conducted therapy facilitated to stop the pathological process in the form of PF, and also prevented the development of severe disabling complications in the child.Conclusion. Differential diagnosis and treatment should be fast and accurate, as the development of PF occurs in mere hours. Diagnostics should include expanded panel of coagulological tests and instrumental examinations, which determines the justifiability of a multidisciplinary approach in the patient management with disorders in the hemostatic system.

Bioprinting Technologies and Bioinks for Vascular Model Establishment.

Clinically, large diameter artery defects (diameter larger than 6 mm) can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene. There are many problems in the construction of small diameter blood vessels (diameter between 1 and 3 mm) and microvessels (diameter less than 1 mm), especially in the establishment of complex vascular models with multi-scale branched networks. Throughout history, the vascularization strategies have been divided into three major groups, including self-generated capillaries from implantation, pre-constructed vascular channels, and three-dimensional (3D) printed cell-laden hydrogels. The first group is based on the spontaneous angiogenesis behaviour of cells in the host tissues, which also lays the foundation of capillary angiogenesis in tissue engineering scaffolds. The second group is to vascularize the polymeric vessels (or scaffolds) with endothelial cells. It is hoped that the pre-constructed vessels can be connected with the vascular networks of host tissues with rapid blood perfusion. With the development of bioprinting technologies, various fabrication methods have been achieved to build hierarchical vascular networks with high-precision 3D control. In this review, the latest advances in 3D bioprinting of vascularized tissues/organs are discussed, including new printing techniques and researches on bioinks for promoting angiogenesis, especially coaxial printing, freeform reversible embedded in suspended hydrogel printing, and acoustic assisted printing technologies, and freeform reversible embedded in suspended hydrogel (flash) technology.

Preclinical in vivo assessment of a cell-free multi-layered scaffold prepared by 3D printing and electrospinning for small-diameter blood vessel tissue engineering in a canine model.

Tissue-engineered vascular grafts (TEVGs) are promising alternatives to existing prosthetic grafts. The objective of this study is to evaluate the clinical feasibility of a novel multi-layered small-diameter vascular graft that has a hierarchical structure. Vascular grafts with elaborately designed composition and architecture were prepared by 3D printing and electrospinning and were implanted into the femoral artery of 5 dogs. The patency of the grafts was assessed using Doppler ultrasonography. After 6 months, the grafts were retrieved and histological and SEM examinations were conducted. During implantation, the grafts exhibited resistance to kinking and no blood seepage thanks to the helical structure of the innermost and outermost layers. The grafts showed a high patency rate and remodelling ability. At 6 months post-implantation, the lumen was endothelialized and middle layers were regenerated by infiltration of smooth muscle cells (SMCs) and deposition of extracellular matrix (ECM). These results suggest that the multi-layered vascular graft may be a promising candidate for small-diameter blood vessel tissue engineering in clinical practice.

Tissue-engineered vascular graft based on a bioresorbable tubular knit scaffold with flexibility, durability, and suturability for implantation.

The tissue-engineered vascular graft (TEVG) is a technology used to recreate a blood vessel by using vascular cells (endothelial cells and smooth muscle cells) and their scaffolds, and is a promising approach as a clinically feasible alternative for small-diameter blood vessel replacement. Since mechanical damage occurs during/after implantation, it needs flexibility and durability to withstand the mechanical damage to be applied. To achieve this, we applied a bioresorbable polyglycolic acid (PGA) fiber-knitted tubular scaffold for vascular endothelial and smooth muscle cell layers. Similar to the native rat aorta, the knitted tubular scaffold (130 μm-thick PGA fiber) exhibited mechanical performance at 150 mN for up to 40% strain for axial stress and at 90 mN for up to 5% strain for circumferential stress. After co-culturing, a vascular barrier comprised of an inner layer of endothelial cells and an outer layer of smooth muscle cells between tubular knits was observed. Up to 93.6% of the co-cultured cells were retained even after bending 50 times, and the suturability to flow liquid without any leakage in various shapes, such as an L-shape or a Y-shape, was acceptable. Taken together, these results support that the PGA tubular knit plays multifunctional roles, such as a porous three-dimensional matrix to attach and grow the vascular cells, and as a flexible and durable scaffold for the suture. Therefore, we suggest that the bioresorbable PGA tubular knit scaffold is a promising scaffold for TEVGs.