Small-caliber Vascular Grafts Research Articles

Interaction of material- and structural elasticity – an approach towards a physiological compliance in small-caliber vascular grafts

Research purpose: The low patency rate (less than 50% at a 5-years follow-up) of commercial vascular grafts is strongly associated with compliance mismatch between graft und native artery. To address this deficit, we investigated the influence of the material and structural elasticity on the compliance behavior of small caliber vascular graft gaining for a stress-strain behavior adapted to the native vessel. Material & Methods: By combining different thermoplastic polycarbonate urethanes (TPU) fibers with different elasticity and non-elastic polyvinylidene fluoride (PVDF) fibers in different warp knitted tubular textile structures, we incorporate material and structural elasticity in a vascular graft (I.D. < 6 mm). The evaluation of the tubular fabrics is performed by determining the compliance properties in a mean pressure range between 20 and 120 mmHg by tensile testing. Results: We identified the draw ration of the TPU fiber production, the stitch course density of the fabric and the thread tension of the TPU yarn during the warp knitting process as statistically highly significant effects ( p < .005) on the compliance. With an adapted setting of those parameters, we were able to improve the compliance of the textile vascular grafts over the entire physiological pressure range (20–120 mmHg) by 400–630 % compared to current clinical ePTFE (expanded polytetrafluoroethylene) grafts towards native vessels. Conclusion: By combining material and structural elasticity in a warp knitted textile structure, we were able to biomimic the compliance towards physiological properties. Our approach can be seen as blueprint to adapt elasticity properties in other implant applications.

Development of a Tri-Layered Vascular Construct and In Vitro Evaluation of Endothelization.

Advances in the development of vascular substitutes for small-sized arteries are ongoing because the present grafts do not entirely meet the requirements of native equivalents and are suboptimal in clinical performance. This study aims to develop a tri-layered vascular construct mimicking natural tissue using polyester blends and to investigate its endothelization through in vitro studies as a potential small-caliber vascular graft. The innermost layer is obtained by dip coating as a tubular porous film with a lumen diameter of 3mm and a pore size of ≤8µm. Circumferentially aligned electrospun fiber (diameter 100-800nm) with a deviation angle of 15° are deposited over the porous film forming the intermediate layer. The random electrospun fibers (diameter 100-1100nm) deviating at different angles are wrapped as the outermost layer. The mechanical properties of the tri-layered vascular construct are determined to be 44.80±14.80MPa for Young's modulus and 4.25±0.75MPa for ultimate tensile strength. MTS and cell behavior studies show that the isolated human umbilical cord vein endothelial cells proliferate and line the lumen of the vascular substitute. The vascular construct developed, with its biomimetic architecture, mechanical features, size, and endothelization, can be tested with in vivo studies.

Development, comparative structural analysis, and first in vivo evaluation of acellular implanted highly compacted fibrin tubes for arterial bypass grafting

The generation of small-caliber vascular grafts remains a significant challenge within the field of tissue engineering. In pursuit of this objective, fibrin has emerged as a promising scaffold material. However, its lack of biomechanical strength has limited its utility in the construction of tissue engineered vascular grafts. We have previously reported about the implementation of centrifugal casting molding to generate compacted fibrin tubes with a highly increased biomechanical strength. In this study, we conducted a structural analysis of compacted fibrin tubes using the open-source software Fiji/BoneJ. The primary aim was to validate the hypothesis that the compaction of fibrin leads to a more complex structure characterized by increased crosslinking of fibrin fibers. Structural analysis revealed a strong correlation between fibrin's structure and its biomechanical strength. Moreover, we enhanced fibrin compaction in a subsequent dehydration process, leading to a significant increase of biomechanical strength. Thus, the presented method in combination with an adequate imaging, e.g., micro-CT, has substantial potential as a powerful tool for quality assurance in the development of fibrin-based vascular grafts. To validate this concept, acellular highly compacted fibrin tubes were implanted as substitutes of a segment of the carotid artery in a sheep model (n = 4). After 6 months explanted segments exhibited distinct remodeling, transitioning into newly formed arteries.

Small-Caliber Vascular Grafts Engineered from Decellularized Leaves and Cross-Linked Gelatin

Despite advances in vascular replacement and repair, fabricating small-diameter vascular grafts with low thrombogenicity and appropriate tissue mechanics remains a challenge. A wide range of platforms have been developed to use plant-derived scaffolds for various applications. Unlike animal tissue, plants are primarily composed of cellulose which can offer a promising, nonthrombogenic alternative capable of promoting cell attachment and redirecting blood flow. By taking advantage of the biocompatibility and mechanical properties of cellulose, we developed small-diameter vascular grafts using decellularized leatherleaf viburnum and cross-linked gelatin. Different terrestrial plant leaves (leatherleaf, spinach, and parsley) were decellularized with sodium dodecyl sulfate, egtazic acid and/or Tergitol, followed by a bleach and Triton X-100 clearing solution, and then evaluated for decellularization efficiency, mechanical integrity, and recellularization potential. Hematoxylin and eosin staining and DNA quantification revealed successful removal of cells in all leatherleaf conditions. Methods of 3D graft fabrication were evaluated, and leatherleaf scaffolds maintained suitable tensile and rupture strength properties. 2D scaffolds and 3D grafts were seeded with rat endothelial cells. Cells remained viable for over 14 days with cell densities comparable to other natural and synthetic scaffolds. This study demonstrates the potential of cost effective and readily available decellularized plants to generate small-diameter vascular grafts capable of recellularization and with suitable mechanical properties.

Production of novel elastic bacterial nanocellulose/polyvinyl alcohol conduits via mercerization and phase separation for small-caliber vascular grafts application

Size and properties of tubular bacterial nanocellulose (BNC) can be regulated by controllable mercerization with thinner tube walls, better mechanical properties, and improved biocompatibility. Although mercerized BNC (MBNC) conduits have considerable potential as small-caliber vascular grafts (<6 mm), poor suture retention and lack of compliance that cannot match natural blood vessels increase the difficulty of surgery and limit potential clinical application. Polyvinyl alcohol (PVA) is a kind of hydrophilic polymer with good biocompatibility and elasticity, which can precipitate in alkaline solutions. In this study, novel elastic mercerized BNC/PVA conduits (MBP) are manufactured combining mercerization of BNC tubes with precipitation and phase separation of PVA with thinner tube wall, improved suture retention, better elasticity, good hemocompatibility and great cytocompatibility. The MBP obtained with 12.5 % PVA is selected for transplantation in a rat abdominal aorta model. For 32 weeks, normal blood flow is observed using Doppler sonographic inspection, which demonstrates long-term patency. Immunofluorescence staining results also indicate the formation of endothelium and smooth muscle layers. The results indicate the introduction of PVA, and its phase separation into mercerization of tubular BNC can endow MBP conduits with better compliance and suture retention, making it a promising candidate for blood vessel replacement.

Vascular cells responses to controlled surface structure and properties of bacterial nanocellulose artificial blood vessel after mercerization

Therapeutic benefits of small caliber artificial blood vessels to cure cardio and cerebrovascular diseases are mainly limited by their low patency during long-term transplantation. Bacterial nanocellulose (BNC), as a natural polysaccharide mainly synthesized by a bacterium Komagataeibatacter xylinus, has shown great potential in small-caliber vascular graft applications due to its shape controllability, and furthermore its physical surface structure can be adjusted with different treatments. However, influences of physical surface structure and properties of BNC conduits on behaviors of vascular cells have not been investigated. In this work, mercerized BNC conduits (MBNC) with different surface roughness and stiffness were constructed by controlled alkali (NaOH) treatment. The changes of surface structures and properties significantly affected the behaviors of vascular cells and gene expression; meanwhile, the cell seeding density also affected the cell responses. After mercerization with NaOH concentration > 10 %, it was observed that the increased stiffness of MBNC decreased several functional gene expressions of human vascular endothelial cells, and the pathological transformation of smooth muscle cells was inhibited. This study demonstrates physical surface structure of MBNC conduits will critically regulate functions and behaviors of vascular cells and it also provides important designing parameters to improve the long-term patency of BNC-based conduits.

A textile-reinforced composite vascular graft that modulates macrophage polarization and enhances endothelial cell migration, adhesion and proliferation in vitro.

At the present time, there is no successful off-the-shelf small-caliber vascular graft (<6 mm) for the repair or bypass of the coronary or carotid arteries. In this study, we engineer a textile-reinforced hydrogel vascular graft. The textile fibers are circularly knitted into a flexible yet robust conduit to serve as the backbone of the composite vascular graft and provide the primary mechanical support. It is embedded in the hydrogel matrix which seals the open structure of the knitted reinforcement and mediates cellular response toward a faster reendothelialization. The mechanical properties of the composite vascular graft, including bursting strength, suture retention strength and radial compliance, significantly surpass the requirement for the vascular graft application and can be adjusted by altering the structure of the textile reinforcement. The addition of hydrogel matrix, on the other hand, improves the survival, adhesion and proliferation of endothelial cells in vitro. The composite vascular graft also enhances macrophage activation and upregulates M1 and M2 related gene expression, which further improves the endothelial cell migration that might favor the reendothelialization of the vascular graft. Taken together, the textile-reinforced hydrogel shows it potential to be a promising scaffold material to fabricate a tissue engineered vascular graft.

The Development of Small-Caliber Vascular Grafts Using Human Umbilical Artery: An Evaluation of Methods.

Due to the prevalence of cardiovascular disease in the United States, small-caliber vascular grafts for coronary bypass surgery continue to be in high demand. Human umbilical arteries, an underutilized resource, were decellularized using zwitterionic (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate [CHAPS]) and ionic (sodium dodecyl sulfate [SDS]) detergents and evaluated as potential vascular grafts. Vessels were tested for decellularization efficacy, mechanical integrity, and recellularization potential. Hematoxylin and eosin staining and DNA quantification revealed moderate to successful removal of cells in both conditions. While CHAPS-decellularized vessels displayed collagen structure most similar to intact tissue, both CHAPS- and SDS-decellularized vessels demonstrated burst pressures lower than that of intact tissue. Alcian Blue staining and sulfated glycosaminoglycan (sGAG) quantification indicated the preservation of sGAG content after both decellularization pathways. Both conditions were also capable of recellularization with human umbilical vein endothelial cells, and the use of a basic fibroblast growth factor treatment did not have a significant effect on the density of adhered cells after 5 days. Whole CHAPS-decellularized vessels were successfully recellularized. Additionally, an evaluation of the effects of freeze-thaw cycles was performed. In summary, human umbilical arteries present a promising alternative for small-caliber vascular grafts due to their high availability and ability to be decellularized and recellularized for safe and successful implantation. Impact Statement Coronary heart disease accounts for one of nine deaths in the United States each year. Bypass surgery has been shown to decrease the risk of heart attack; however, many patients do not have a suitable saphenous vein, which is required to redirect blood flow around their blocked arteries. In this study, we evaluate decellularized umbilical artery as a potential small-diameter vascular graft based on its mechanical properties and its recellularization potential.

Construction of spider silk protein small-caliber tissue engineering vascular grafts based on dynamic culture and its performance evaluation.

Tissue engineering is an alternative method for preparing small-caliber (<6 mm) vascular grafts. Dynamic mechanical conditioning is being researched as a method to improve mechanical properties of tissue engineered blood vessels. This method attempts to induce unique reaction in implanted cells that regenerate the matrix around them, thereby improving the overall mechanical stability of the grafts. In this study, we used a bioreactor to seed endothelial cells and smooth muscle cells into the inner and outer layers of the electrospun spider silk protein scaffold respectively to construct vascular grafts. The cell proliferation, mechanical properties, blood compatibility and other indicators of the vascular grafts were characterized in vitro. Furthermore, the vascular grafts were implanted in Sprague Dawley rats, and the vascular grafts' patency, extracellular matrix formation, and inflammatory response were evaluated in vivo. We aimed to construct spider silk protein vascular grafts with the potential for in vivo implantation by using a pulsating flow bioreactor. The results showed that, when compared with the static culture condition, the dynamic culture condition improved cell proliferation on vascular scaffolds and enhanced mechanical function of vascular scaffolds. In vivo experiments also showed that the dynamic culture of vascular grafts was more beneficial for the extracellular matrix deposition and anti-thrombogenesis, as well as reducing the inflammatory response of vascular grafts. In conclusion, dynamic mechanical conditioning aid in the resolution of challenges impeding the application of electrospun scaffolds and have the potential to construct small-caliber blood vessels with regenerative function for cardiovascular tissue repair.

Polyvinyl alcohol coating prevents platelet adsorption and improves mechanical property of polycaprolactone-based small-caliber vascular graft.

The low patency of synthetic vascular grafts hinders their practical applicability. Polyvinyl alcohol (PVA) is a non-toxic, highly hydrophilic polymer; thus, we created a PVA-coated polycaprolactone (PCL) nanofiber vascular graft (PVA–PCL graft). In this study, we examine whether PVA could improve the hydrophilicity of PCL grafts and evaluate its in vivo performance using a rat aorta implantation model. A PCL graft with an inner diameter of 1 mm is created using electrospinning (control). The PCL nanofibers are coated with PVA, resulting in a PVA–PCL graft. Mechanical property tests demonstrate that the PVA coating significantly increases the stiffness and resilience of the PCL graft. The PVA–PCL surface exhibits a much smaller sessile drop contact angle when compared with that of the control, indicating that the PVA coating has hydrophilic properties. Additionally, the PVA–PCL graft shows significantly less platelet adsorption than the control. The proposed PVA–PCL graft is implanted into the rat’s abdominal aorta, and its in vivo performance is tested at 8 weeks. The patency rate is 83.3% (10/12). The histological analysis demonstrates autologous cell engraftment on and inside the scaffold, as well as CD31/α-smooth muscle positive neointima regeneration on the graft lumen. Thus, the PVA–PCL grafts exhibit biocompatibility in the rat model, which suggests that the PVA coating is a promising approach for functionalizing PCL.

Coagulation/anticoagulation-regulable and tough extracellular matrix hydrogels

Many active proteins and growth factors exist in extracellular matrix (ECM), regulating important physiological processes in the body. The conversion of ECM into hydrogels will significantly expand their application scope. Given the complexity of the environment in vivo, fabrication of ECM hydrogels with regulable coagulation/anticoagulation is very important yet challenging. Herein, we utilize phosphate buffer (PBS) as a concentration switch to realize the coagulation/anticoagulation transformation of ECM hydrogels. Benefiting from their regulable characteristic, these ECM hydrogels are respectively converted into hemostatic sponges/powders and tough anticoagulant films. The tensile strength of the film reached 39.23 ± 3.21 MPa. Especially, blood flow signals were still detected after two weeks transplantation of ECM films onto rat carotid arteries (diameter < 1 mm) as a vascular patch, suggesting the potential application of ECM anticoagulant films in small-caliber vascular grafts. This work provided a facile and sustainable strategy for developing ECM hydrogels with regulable coagulant/anticoagulant properties.

Mercerization of tubular bacterial nanocellulose for control of the size and performance of small-caliber vascular grafts

Bacterial nanocellulose (BNC) is a natural polysaccharide synthesized principally by Komagataeibatacter xylinus which can be formed into tubes and other shapes through the use of special bioreactors. Although tubular BNC has considerable potential as a small-caliber vascular graft (<6 mm), its poor mechanical properties in its hydrogel form, lack of compliance, and its thick walls that do not match natural vessels limit their potential clinical use and long-term patency rate after implantation. Mercerization is an approach in which an alkaline treatment changes the chemistry of BNC products. Following mercerization, tubular BNC grafts exhibited greater mechanical strength combined with thinner walls. Volumetric reduction of the tubular BNC was effective (by nearly 90%) when using a NaOH concentration greater than 10% (w/v), which caused fewer platelets to adhere to the luminal surface. Mercerized tubular BNC (MBNC) promoted the proliferation of endothelial cells in vitro. The MBNC obtained using 20% NaOH was selected for transplantation within a rat abdominal aorta model. Normal blood flow was observed for 16 weeks, indicating that the MBNC conduit maintained long-term patency. The results indicate that mercerization can control the size of tubular BNC and thus the MBNC conduit is a promising candidate for blood vessel replacement.

Toxicological and Sensitization Studies of Novel Vascular Prostheses Made of Bacterial Nanocellulose Modified with Chitosan (MBC) for Application as the Tissue-Engineered Blood Vessels

BackgroundTissue-engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases in humankind by providing small caliber vascular grafts. The study evaluates biocompatibility and bioaffinity of vascular prostheses made from chitosan-modified bacterial cellulose (MBC) as potential scaffolds for TEBV.MethodsDuring the study, acute oral toxicity, up-and-down procedure (UDP), OECD test No. 425 on 10 Imp:WIST rats, intradermal reactivity on three Imp:BN albino rabbits, and sensitization on 15 Imp:DH guinea pigs were performed. The local effects were determined 1 month after intramuscular implantation of prostheses in 30 Imp:WIST rats. Histopathological and pathomorphological studies were conducted following complete removal of implants with peri-implant tissue.ResultsThere were no signs of toxicity; the median lethal oral dose (LD50) was greater than 2 g/kg body weight for the rats. No allergic reactions were observed in the case of the guinea pig maximization test. Vascular grafts did not induce significant reactive changes in intradermal reactivity test (Main Irritation Index value 0.03) and do not induce inflammatory changes or hyperplasia of the muscle tissue surrounding the implant. Histopathological examination revealed ingrown vascular-connective bands.ConclusionsTubes made of MBC offer strong potential for use in future TEBV programs for vascular surgery.Lay SummaryCurrently, the number of autologous grafts for coronary artery disease and for peripheral artery disease is limited. Particularly materials that will have contact with blood must comply with certain requirements such as mechanical strength, biocompatibility, and no potential to evoke adverse reactions. Bacterial nanocellulose modified with chitosan (MBC) due to its mechanical and biological properties is a promising material for replacing small-diameter vessels grafts. Although previous studies have not shown the toxicity of nanocellulose, we want to check whether medical products based on MBC will be safe when testing in vivo. Thirty Imp:WIST rats and 15 Imp:DH guinea pigs were subject of thorough analysis of potential toxicological and sensitization effect that may develop after applying vascular prostheses made from MBC to living organism. The analysis involved also histopathological and pathomorphological studies following complete removal of implants with peri-implant tissue. The results show that MBC prostheses do not cause any allergic, intradermal reactions and finally, do not display acute toxicity towards the organism in which it is implanted. Moreover, they had not induced inflammatory changes or hyperplasia of the muscle tissue surrounding the implantation sites, thus showing good biocompatibility. Obtained results were discussed with other available studies investigating various aspects of bacterial cellulose or modified bacterial cellulose influence on cells and tissues in both in vitro and in vivo studies. This is the first study analyzing the toxicological and sensitization effect which MBC may evoke and confirm the strong potential for use in future TEBV programs for vascular surgery.Graphical

Endothelial Cell-Mediated Gene Delivery for In Situ Accelerated Endothelialization of a Vascular Graft.

As an urgently needed device for vascular diseases, the small-diameter vascular graft is limited by high thrombogenicity in clinical applications. Rapid endothelialization is a promising approach to construct an antithrombogenic inner surface of the vascular graft. The main bottleneck for rapid endothelialization is the adhesion, migration, and proliferation of endothelial cells (ECs) in situ of the small-diameter vascular graft. Herein, we innovatively fabricated an intelligent gene delivery small-caliber vascular graft based on electrospun poly(lactic acid-co-caprolactone) and gelatin for rapid in situ endothelialization. The graft surface was co-modified with EC adhesive peptide of Arg-Glu-Asp-Val (REDV) and responsive gene delivery system. REDV can selectively adhere ECs onto the graft surface; subsequently, the overexpressed matrix metalloproteinase by ECs can effectively cleave the linker peptide GPQGIWGQ-C; and finally, the gene complexes were intelligently and enzymatically released from the graft surface, and thereby, the gene can efficiently transfect ECs. Importantly, this enzymatically releasing gene surface has been proven to be safe and temporarily stable in blood flow owing to the biotin-avidin interaction to immobilize gene complexes on the inner surface of vascular grafts through the GPQGIWGQ-C peptide linker. It has the advantage of specifically adhering the ECs to the surface and smartly transfecting them with high transfection efficiency. The co-modified surface has been demonstrated to accelerate the luminal endothelialization in vivo, which might be attributed to the synergistic effect of REDV and effective gene transfection. Particularly, the intelligent and responsive gene release surface will open a new avenue to enhance the endothelialization of blood-contacting devices.

Effects of recipient age, heparin release and allogeneic bone marrow-derived stromal cells on vascular graft remodeling

Small-caliber vascular grafts are used in a wide range of clinical conditions. However, there remains a substantial unfulfilled need for readily-available, synthetic vascular grafts with high long-term patency rate. To fulfill the translational goal for bioengineered vascular grafts, important considerations for the pre-clinical evaluation include the graft design, cell incorporation and selection of an animal model. To assess the three factors, we used vascular grafts consisting of core/shell-structured microfibers of polycaprolactone/gelatin with a thin polycaprolactone overlay. The respective influences of the heparin release mode, animal age, and allogeneic bone marrow-derived stromal cells (MSCs) seeded in the lumen on the graft remodeling were assessed after four-and-half-month implantation on an interposition graft of abdominal aorta model. Except two rats dying from graft-unrelated issues, all other rats (18 out of 20) showed good graft patency upon explantation. The cell phenotype, matrix content and structure in the neotissues around the graft, as well as the flow perfusion through the graft were examined. More grafts in the aged rats showed local narrowing and flow incongruence than the other grafts in young adult rats. Compared to acellular grafts, cellular grafts showed efficient recruitment of vascular cells to form more organized structures with elastin in the vascular wall. Endothelialization and α−smooth muscle actin-positive cells were shown in all four types of vascular grafts. This study revealed the significant effects of MSC and recipient age but not heparin release pattern on graft remodeling. Statement of significanceThe vascular graft is a mainstream of surgical intervention to treat vascular diseases. Currently, vascular grafts, particularly small-diameter ones, still show high failure rates. This study has evaluated the respective impacts of heparin release pattern, allogeneic bone marrow-derived stromal cell seeding, and recipient age on the long-term remodeling of vascular grafts. There is a dearth of literature which considers the recipient age as an influencing factor for vascular grafting. However, adults particularly elderly constitute the majority of vascular graft recipients in the “real” clinical environment. While juvenile animals were widely used for graft evaluations, this study involved adult animals. The study outcomes provided important implications regarding graft designs and evaluation approaches.

Vascular Tissue Engineering: Polymers and Methodologies for Small Caliber Vascular Grafts

Cardiovascular disease is the most common cause of death in the world. In severe cases, replacement or revascularization using vascular grafts are the treatment options. While several synthetic vascular grafts are clinically used with common approval for medium to large-caliber vessels, autologous vascular grafts are the only options clinically approved for small-caliber revascularizations. Autologous grafts have, however, some limitations in quantity and quality, and cause an invasiveness to patients when harvested. Therefore, the development of small-caliber synthetic vascular grafts (<5 mm) has been urged. Since small-caliber synthetic grafts made from the same materials as middle and large-caliber grafts have poor patency rates due to thrombus formation and intimal hyperplasia within the graft, newly innovative methodologies with vascular tissue engineering such as electrospinning, decellularization, lyophilization, and 3D printing, and novel polymers have been developed. This review article represents topics on the methodologies used in the development of scaffold-based vascular grafts and the polymers used in vitro and in vivo.

Improved Performance of Bacterial Nanocellulose Conduits by the Introduction of Silk Fibroin Nanoparticles and Heparin for Small-Caliber Vascular Graft Applications.

Bacterial nanocellulose (BNC) is a promising material for small-caliber artificial blood vessels, although promoting its anticoagulant properties with more rapid endothelialization would improve long-term patency. Silk fibroin nanoparticles (SFNP) were introduced into the luminal wall surface of BNC conduits both with and without heparin (Hep) through pressurization followed by fixation. Hep was introduced in two ways: (1) embedded within SF nanoparticles to form SF-HepNPs for construction of the BNC-SF-HepNP conduit and (2) chemically grafted onto BNC and BNC-SFNP to form BNC-Hep and BNC-SFNP-Hep conduits. Fourier transform infrared spectroscopy confirmed the formation of SF-HepNPs, although they did not incorporate into the fibrillar network due to their large size. Hep was successfully grafted onto BNC and BNC-SFNP, verified by toluidine blue staining. The hemocompatibility and cytocompatibility of the five samples (BNC, BNC-SFNP, BNC-SF-HepNP, BNC-Hep, and BNC-SFNP-Hep conduits) were compared in vitro. The heparinized BNC-Hep and BNC-SFNP-Hep conduits improved the anticoagulant properties, and BNC-SFNP-Hep promoted human umbilical vein endothelial cell proliferation but also controlled excessive human arterial smooth muscle cell proliferation, assisting rapid endothelialization and improving lumen patency. No significant inflammatory reaction or material degradation was observed after subcutaneous implantation for 4 weeks. Autogenous tissues were observed around the conduits, and cells infiltrated into the edges of all samples, the BNC-SFNP conduit causing the deepest infiltration, providing an appropriate microenvironment for angiogenesis when used in small-caliber blood vessel applications. Few inflammatory cells were found around the BNC-Hep and BNC-SFNP-Hep conduits. Thus, the anticoagulant properties of the BNC-SFNP-Hep conduit and its stimulation of endothelialization suggest that it has great potential in clinical applications as a small-caliber artificial blood vessel.

Merging 3D printing with electrospun biodegradable small-caliber vascular grafts immobilized with VEGF

The major challenge of commercially available vascular substitutes comes from their limitations in terms of hydrophobic surface, which is hostile to cell growth. To date, tissue-engineered and synthetic grafts have not translated well to clinical trials when looking at small diameters. We conceptualized a cell-free structurally reinforced biodegradable vascular graft recapitulating the anisotropic feature of a native blood vessel. The nanofibrous scaffold is designed in such a way that it will gradually degrade systematically to yield a neo-vessel, facilitated by an immobilized bioactive molecule-vascular endothelial growth factor (VEGF). The nano-topographic cue of the device is capable of direct host cell infiltration. We evaluated the burst pressure, histology, hemocompatibility, compression test, and mechanical analysis of the new graft. The graft implanted into the carotid artery of a porcine model demonstrated a good patency rate as early as two week post-implantation. This graft reinforced design approach when employed in vascular tissue engineering might strongly influencing regenerative medicine.

A hybrid vascular graft harnessing the superior mechanical properties of synthetic fibers and the biological performance of collagen filaments.

Tissue-engineered small caliber vascular grafts have attracted much research attention as a viable alternative to traditional vascular grafts with their biocompatibility and potential to achieve complete healing. However, the major challenge is to fabricate a scaffold with both satisfactory mechanical properties and fast endothelialization. In this study, a hybrid tubular vascular tissue engineered scaffold has been circular-knitted using novel electrochemically aligned collagen (ELAC) filaments plied together with traditional poly(lactic acid) (PLA) yarn. The collagen component was able to promote the recruitment and proliferation of endothelial cells by increasing the initial cell adhesion 10-fold and the eventual cell population 3.2 times higher than the PLA scaffold alone. At the same time, the PLA yarn was able to provide sufficient mechanical strength and structural stability, as well as facilitate scaffold fabrication on high speed textile production equipment. The tubular hybrid scaffold exhibited excellent bursting strength (1.89±0.43MPa) and suture retention strength (10.86±0.49N), and had comparable compliance (3.98±1.94%/100mmHg) to that of the coronary artery (3.8±0.3%/100mmHg) under normotensive pressure. With its excellent mechanical and biological performance, this prototype hybrid scaffold is a promising candidate for the construction of a clinically successful and easily translatable tissue-engineered small caliber vascular graft.

Structurally Reinforced Biodegradable Antithrombotic Small-Caliber Vascular Grafts Immobilized with VEGF to Accelerate Endothelialization: When 3D Printing Meets Electrospun Fiber

The major challenge of commercially available vascular substitutes come from their limitations in terms of good mechanical strength and host remodeling. To date, tissue-engineered and synthetic grafts have not translated well to clinical trials when looking at small diameters. We conceptualized a cell-free structurally reinforced biodegradable vascular graft recapitulating the anisotropic feature of native blood vessel by using nanofibrous scaffold that will gradually degrade systematically to yield a neo-vessel, facilitated by an immobilized bioactive molecule-vascular endothelial growth factor (VEGF). The nanotopographic cue of the device is capable to directs host cell infiltration. We evaluated the burst pressure, Histology, hemocompatibility, compression test and mechanical analysis of the new graft. Hence, we proposed that future long-term studies of this technology on porcine models due to their similar vasculature regeneration to humans is needed prior to clinical translation. This acellular off-the-shelf approach will mark a paradigm shift from the current dominant focus on cell incorporation in vascular tissue engineering thus strongly influencing regenerative medicine as we move forward in this new decade.