Small-diameter Vascular Grafts Research Articles

Design and Synthesis of P(AAm-co-NaAMPS)-Alginate-Xanthan Hydrogels and the Study of Their Mechanical and Rheological Properties in Artificial Vascular Graft Applications

Cardiovascular diseases (CVDs) are the number one cause of mortality among non-communicable diseases worldwide. Expanded polytetrafluoroethylene (ePTFE) is a widely used material for making artificial vascular grafts to treat CVDs; however, its application in small-diameter vascular grafts is limited by the issues of thrombosis formation and intimal hyperplasia. This paper presents a novel approach that integrates a hydrogel layer on the lumen of ePTFE vascular grafts through mechanical interlocking to efficiently facilitate endothelialization and alleviate thrombosis and restenosis problems. This study investigated how various gel synthesis variables, including N,N’-Methylenebisacrylamide (MBAA), sodium alginate, and calcium sulfate (CaSO4), influence the mechanical and rheological properties of P(AAm-co-NaAMPS)-alginate-xanthan hydrogels intended for vascular graft applications. The findings obtained can provide valuable guidance for crafting hydrogels suitable for artificial vascular graft fabrication. The increased sodium alginate content leads to increased equilibrium swelling ratios, greater viscosity in hydrogel precursor solutions, and reduced transparency. Adding more CaSO4 decreases the swelling ratio of a hydrogel system, which offsets the increased swelling ratio caused by alginate. Increased MBAA in the hydrogel system enhances both the shear modulus and Young’s modulus while reducing the transparency of the hydrogel system and the pore size of freeze-dried samples. Overall, Hydrogel (6A12M) with 2.58 mg/mL CaSO4 was the optimal candidate for ePTFE–hydrogel vascular graft applications due to its smallest pore size, highest shear storage modulus and Young’s modulus, smallest swelling ratio, and a desirable precursor solution viscosity that facilitates fabrication.

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.

Fabric-Enhanced Vascular Graft with Hierarchical Structure for Promoting the Regeneration of Vascular Tissue.

Natural blood vessels have completed functions, including elasticity, compliance, and excellent antithrombotic properties because of their mature structure. To replace damaged blood vessels, vascular grafts should perform these functions by simulating the natural vascular structures. Although the structures of natural blood vessels are thoroughly explored, constructing a small-diameter vascular graft that matches the mechanical and biological properties of natural blood vessels remains a challenge. A hierarchical vascular graft is fabricated by Electrospinning, Braiding, and Thermally induced phase separation (EBT) processes, which could simulate the structure of natural blood vessels. The internal electrospun structure facilitates the adhesion of endothelial cells, thereby accelerating endothelialization. The intermediate PLGA fabric exhibits excellent mechanical properties, which allow it to maintain its shape during long-term transplantation and prevent graft expansion. The external macroporous structure is beneficial for cell growth and infiltration. Blood vessel remodeling aims to combine a structure that promotes tissue regeneration with anti-inflammatory materials. The results in vitro demonstrated that it EBT vascular graft (EBTVG) has matched the mechanical properties, reliable cytocompatibility, and the strongest endothelialization in situ. The results in vitro and replacement of the resected artery in vivo suggest that the EBTVG combines different structural advantages with biomechanical properties and reliable biocompatibility, significantly promoting the stabilization and regeneration of vascular endothelial cells and vascular smooth muscle cells, as well as stabilizing the blood microenvironment.

Long-term observation of polycaprolactone small-diameter vascular grafts with thickened outer layer and heparinized inner layer in rabbit carotid arteries

In our previous study, the pristine bilayer small-diameter in situ tissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 μm and 202 μm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneurysms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regeneration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 μm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.

3D printed grafts with gradient structures for organized vascular regeneration

Synthetic vascular grafts suitable for small-diameter arteries (<6 mm) are in great need. However, there are still no commercially available small-diameter vascular grafts (SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation. When designing SDVGs, many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer (SML). To facilitate rapid SML regeneration, a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries. Bioinspired by the collagen alignment of SML, the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment, which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization. The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength. One month after implantation, the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts, with a compliance (8.9%) approaching that of natural arteries (11.36%) and significantly higher than that of electrospun ones (1.9%). The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML. Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

Small-diameter vascular graft composing of core-shell structured micro-nanofibers loaded with heparin and VEGF for endothelialization and prevention of neointimal hyperplasia

Despite the significant progress made in recent years, clinical issues with small-diameter vascular grafts related to low mechanical strength, thrombosis, intimal hyperplasia, and insufficient endothelialization remain unresolved. This study aims to design and fabricate a core-shell fibrous small-diameter vascular graft by co-axial electrospinning process, which will mechanically and biologically meet the benchmarks for blood vessel replacement. The presented graft (PGHV) comprised polycaprolactone/gelatin (shell) loaded with heparin-VEGF and polycaprolactone (core). This study hypothesized that the shell structure of the fibers would allow rapid degradation to release heparin-VEGF, and the core would provide mechanical strength for long-term application. Physico-mechanical evaluation, in vitro biocompatibility, and hemocompatibility assays were performed to ensure safe in vivo applications. After 25 days, the PGHV group released 79.47 ± 1.54% of heparin and 86.25 ± 1.19% of VEGF, and degradation of the shell was observed but the core remained pristine. Both the control (PG) and PGHV groups demonstrated robust mechanical properties. The PGHV group showed excellent biocompatibility and hemocompatibility compared to the PG group. After four months of rat aorta implantation, PGHV exhibited smooth muscle cell regeneration and complete endothelialization with a patency rate of 100%. The novel core-shell structured graft could be pivotal in vascular tissue regeneration application.

Macromolecular Crowding Enhances Matrix Protein Deposition in Tissue-Engineered Vascular Grafts.

Successful in vitro culture of small-diameter tissue-engineered vascular grafts (TEVGs) requires rapid deposition of biomacromolecules secreted by vascular smooth muscle cells in a polyglycolic acid mesh scaffold's three-dimensional (3D) porous environment. However, common media have lower crowding conditions than in vivo tissue fluids. In addition, during the early stages of construction, most of the biomolecules secreted by the cells into the medium are lost, which negatively affects the TEVG culture process. In this study, we propose the use of macromolecular crowding (MMC) to enhance medium crowding to improve the deposition and self-assembly efficiency of major biomolecules in the early stages of TEVG culture. The addition of carrageenan significantly increased the degree of MMC in the culture medium without affecting cell viability, proliferation, and metabolic activity. Protein analysis demonstrated that the deposition of collagen types I and III and fibronectin increased significantly in the cell layers of two-dimensional and 3D smooth muscle cell cultures after the addition of a MMC agent. Collagen type I in the culture medium decreased significantly compared with that in the medium without a MMC agent. Scanning electron microscopy demonstrated that MMC agents considerably enhanced the formation of matrix protein structures during the early stages of 3D culture. Hence, MMC modifies the crowding degree of the culture medium, resulting in the rapid formation of numerous matrix proteins and fiber structures. Impact Statement Small-diameter tissue-engineered vascular grafts (TEVGs) are one of the most promising means of treating cardiovascular diseases; however, the in vitro construction of TEVGs has some limitations, such as slow deposition of extracellular matrix (ECM), long culture period, and poor mechanical properties. We hypothesized that macromolecular crowding can increase the crowding of the culture medium to construct a more bionic microenvironment, which enhances ECM deposition in the medium to the cell layer and reduces collagen loss, accelerating and enhancing TEVG culture and construction in vitro.

Antioxidant and Trilayered Electrospun Small-Diameter Vascular Grafts Maintain Patency and Promote Endothelialisation in Rat Femoral Artery.

Vascular grafts with a small diameter encounter inadequate patency as a result of intimal hyperplasia development. In the current study, trilayered electrospun small-diameter vascular grafts (PU-PGACL + GA) were fabricated using a poly(glycolic acid) and poly(caprolactone) blend as the middle layer and antioxidant polyurethane with gallic acid as the innermost and outermost layers. The scaffolds exhibited good biocompatibility and mechanical properties, as evidenced by their 6 MPa elastic modulus, 4 N suture retention strength, and 2500 mmHg burst pressure. Additionally, these electrospun grafts attenuated cellular oxidative stress and demonstrated minimal hemolysis (less than 1%). As a proof-of-concept, the preclinical evaluation of the grafts was carried out in the femoral artery of rodents, where the conduits demonstrated satisfactory patency. After 35 days of implantation, ultrasound imaging depicted adequate blood flow through the grafts, and the computed vessel diameter and histological staining showed no significant stenosis issue. Immunohistochemical analysis confirmed matrix deposition (38% collagen I and 16% elastin) and cell infiltration (42% for endothelial cells and 55% for smooth muscle cells) in the explanted grafts. Therefore, PU-PGACL + GA showed characteristics of a clinically relevant small-diameter vascular graft, facilitating re-endothelialization while preserving the anticoagulant properties of the synthetic blood vessels.

Fabrication and biomechanical characterization of a spider silk reinforced fibrin-based vascular prosthesis

With fibrin-based vascular prostheses, vascular tissue engineering offers a promising approach for the fabrication of biologically active regenerative vascular grafts. As a potentially autologous biomaterial, fibrin exhibits excellent hemo- and biocompatibility. However, the major problem in the use of fibrin constructs in vascular tissue engineering, which has so far prevented their widespread clinical application, is the insufficient biomechanical stability of unprocessed fibrin matrices.In this proof-of-concept study, we investigated to what extent the addition of a spider silk network into the wall structure of fibrin-based vascular prostheses leads to an increase in biomechanical stability and an improvement in the biomimetic elastic behavior of the grafts. For the fabrication of hybrid prostheses composed of fibrin and spider silk, a statically cast tubular fibrin matrix was surrounded with an envelope layer of Trichonephila edulis silk using a custom built coiling machine. The fibrin matrix was then compacted and pressed into the spider silk network by transluminal balloon compression.This manufacturing process resulted in a hybrid prosthesis with a luminal diameter of 4 mm. Biomechanical characterization revealed a significant increase in biomechanical stability of spider silk reinforced grafts compared to exclusively compacted fibrin segments with a mean burst pressure of 362 ± 74 mmHg vs. 213 ± 14 mmHg (p < 0.05). Dynamic elastic behavior of the spider silk reinforced grafts was similar to native arteries. In addition, the coiling with spider silk allowed a significant increase in suture retention strength and resistance to external compression without compromising the endothelialization capacity of the grafts.Thus, spider silk reinforcement using the abluminal coiling technique represents an efficient and reproducible technique to optimize the biomechanical behavior of small-diameter fibrin-based vascular grafts.

Characterization and promotion of endothelialization of Bombyx mori silk fibroin functionalized with REDV peptide

In the development of small-diameter vascular grafts, it is crucial to achieve early-stage endothelialization to prevent thrombus formation and intimal hyperplasia. Silk fibroin (SF) from Bombyx mori is commonly used for such grafts. However, there is a need to expedite endothelialization post-implantation. In this study, we functionalized SF with Arg-Glu-Asp-Val (REDV) (SF + REDV) using cyanuric chloride to enhance endothelialization. The immobilization of REDV onto SF was confirmed and the amount of immobilized REDV could be calculated by 1H NMR. Furthermore, the conformational changes in Tyr, Ser, and Ala residues in [3-13C]Tyr- and [3-13C]Ser-SF due to REDV immobilization were monitored using 13C solid-state NMR. The REDV immobilized onto the SF film was found to be exposed on the film's surface, as confirmed by biotin-avidin system. Cell culture experiments, including adhesiveness, proliferation, and extensibility, were conducted using normal human umbilical vein endothelial cells (HUVEC) and normal human aortic smooth muscle cells (HAoSMC) on both SF and SF + REDV films to evaluate the impact of REDV on endothelialization. The results indicated a trend towards promoting HUVEC proliferation while inhibiting HAoSMC proliferation. Therefore, these findings suggest that SF + REDV may be more suitable than SF alone for coating small-diameter SF knitted tubes made of SF threads.

A polyurethane-based hydrophilic elastomer with multi-biological functions for small-diameter vascular grafts

Thrombosis and intimal hyperplasia (IH) are two major problems faced by the small-diameter vascular grafts. Mimicking the native endothelium and physiological elasticity of blood vessels is considered an ideal strategy. Polyurethane (PU) is suitable for vascular grafts in mechanics because of its molecular designability and elasticity; however, it generally lacks the endothelium-like biofunctions and hydrophilicity. To solve this contradiction, a hydrophilic PU elastomer is developed by crosslinking the hydrophobic hard-segment chains containing diselenide with diaminopyrimidine-capped polyethylene glycol (PEG). In this network, the hydrophobic aggregation occurs underwater due to the uninterrupted hard-segment chains, leading to a significant self-enhancement in mechanics, which can be tailored to the elasticity similar to natural vessels by adjusting the crosslinking density. A series of in vitro studies confirm that the hydrophilicity of PEG and biological activities of aminopyrimidine and diselenide give the PU multi-biological functions similar to the native endothelium, including stable catalytic release of nitric oxide (NO) in the physiological level; anti-adhesion and anti-activation of platelets; inhibition of migration, adhesion, and proliferation of smooth muscle cells (SMCs); and antibacterial effect. In vivo studies further prove the good histocompatibility with both significant reduction in immune response and calcium deposition. Statement of significanceConstructing small-diameter vascular grafts similar to the natural vessels is considered an ideal method to solve the restenosis caused by thrombosis and intimal hyperplasia (IH). Because of the long-term stability, bulk modification is more suitable for implanted materials, however, how to achieve the biofunctions, hydrophilicity, and elasticity simultaneously is still a big challenge. In this work, a kind of polyurethane-based elastomer has been designed and prepared by crosslinking the functional long hard-segment chains with PEG soft segments. The underwater elasticity based on hydration-induced stiffening and the multi-biological functions similar to the native endothelium are compatible with natural vessels. Both in vitro and in vivo experiments demonstrate the potential of this PU as small-diameter vascular grafts.

Optimization of Electrospun Bilayer Vascular Grafts through Assessment of the Mechanical Properties of Monolayers.

Small-diameter vascular grafts must be obtained with the most appropriate materials and design selection to harmoniously display a variety of features, including adequate tensile strength, compliance, burst strength, biocompatibility, and biodegradability against challenging physiological and hemodynamic conditions. In this study, monolayer vascular grafts with randomly distributed or radially oriented fibers are produced using neat, blended, and copolymer forms of polycaprolactone (PCL) and poly(lactic acid) (PLA) via the electrospinning technique. The blending ratio is varied by increasing 10 in the range of 50-100%. Bilayer graft designs are realized by determining the layers with a random fiber distribution for the inner layer and radial fiber orientation for the outer layer. SEM analysis, wall thickness and fiber diameter measurements, tensile strength, elongation, burst strength, and compliance tests are done for both mono- and bilayer scaffolds. The findings revealed that the scaffolds made of neat PCL show more flexibility than the neat PLA samples, which possess higher tensile strength values than neat PCL scaffolds. Also, in blended samples, the tensile strength values do not show a significant improvement, whereas the elongation values are enhanced in tubular samples, depending on the blending ratio. Also, neat poly(l-lactide-co-caprolactone) (PLCL) samples have both higher elongation and strength values than neat and blended scaffolds, with some exceptions. The blended specimens comprising a combination of PCL and PLA, with blending ratios of 80/20 and 70/30, exhibited the most elevated burst pressures. Conversely, the PLCL scaffolds demonstrated superior compliance levels. These findings suggest that the blending approach and fiber orientation offer enhanced burst strength, while copolymer utilization in PLCL scaffolds without fiber alignment enhances their compliance properties. Thus, it is evident that using a copolymer instead of blending PCL and PLA and combining the PLCL layer with PCL and PLA monolayers in bilayer vascular graft design is promising in terms of mechanical and biological properties.

Development of 3D printed electrospun vascular graft loaded with tetramethylpyrazine for reducing thrombosis and restraining aneurysmal dilatation.

Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations. Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety. Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed. The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.

A small-diameter vascular graft promotes rapid and benign remodeling of the neointima through dual release of nitric oxide and hydrogen sulfide

Coronary artery bypass grafting often requires autologous veins as alternatives. The limited source and problem of over-expansion are major obstacles for vein grafts, which could be solved by small-diameter artificial vascular graft. However, their clinical application is limited by thrombosis and restenosis caused by incomplete endothelialization and abnormal smooth muscle cells (SMCs) proliferation. Nitric oxide (NO) and hydrogen sulfide (H2S) are crucial signaling molecules in the cardiovascular system, known to regulate endothelial cells(ECs) and SMCs proliferation, migration, reduce oxidative stress, and inhibit inflammation to prevent intimal hyperplasia. In this study, we developed a new method to prepare a keratin based H2S donor(KAT) complexed with copper ions and electrospun it with PCL to prepare PCL/KAT-Cu small-diameter tissue-engineered vascular graft, which is capable of dual release of NO and H2S. We investigated the effects of NO and H2S release on human umbilical vein endothelial cells (HUVECs) and human umbilical arterial smooth muscle cells(HUASMCs) proliferation and migration, evaluated the graft's selectivity for HUVECs, and assessed its effects on macrophage phenotypic transitions and its protective effect on HUVECs under reactive oxygen species (ROS) conditions. Additionally, we tested the graft's ability to rapidly endothelialize under shear force using an in vitro 3D-perfusion system. After one month of in situ transplantation in rat abdominal aorta, the PCL/KAT-Cu small-diameter tissue-engineered vascular grafts demonstrated satisfactory intimal remodeling, comparable to natural blood vessels. In conclusion, our study presents a promising new strategy for remodeling small-diameter vascular grafts.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

Temporal Changes in the Surface Chemistry and Topography of Reactive Ion Plasma-Treated Poly(vinyl alcohol) Alter Endothelialization Potential.

Synthetic small-diameter vascular grafts (<6 mm) are used in the treatment of cardiovascular diseases, including coronary artery disease, but fail much more readily than similar grafts made from autologous vascular tissue. A promising approach to improve the patency rates of synthetic vascular grafts is to promote the adhesion of endothelial cells to the luminal surface of the graft. In this study, we characterized the surface chemical and topographic changes imparted on poly(vinyl alcohol) (PVA), an emerging hydrogel vascular graft material, after exposure to various reactive ion plasma (RIP) surface treatments, how these changes dissipate after storage in a sealed environment at standard temperature and pressure, and the effect of these changes on the adhesion of endothelial colony-forming cells (ECFCs). We showed that RIP treatments including O2, N2, or Ar at two radiofrequency powers, 50 and 100 W, improved ECFC adhesion compared to untreated PVA and to different degrees for each RIP treatment, but that the topographic and chemical changes responsible for the increased cell affinity dissipate in samples treated and allowed to age for 230 days. We characterized the effect of aging on RIP-treated PVA using an assay to quantify ECFCs on RIP-treated PVA 48 h after seeding, atomic force microscopy to probe surface topography, scanning electron microscopy to visualize surface modifications, and X-ray photoelectron spectroscopy to investigate surface chemistry. Our results show that after treatment at higher RF powers, the surface exhibits increased roughness and greater levels of charged nitrogen species across all precursor gases and that these surface modifications are beneficial for the attachment of ECFCs. This study is important for our understanding of the stability of surface modifications used to promote the adhesion of vascular cells such as ECFCs.

Clopidogrel-loaded vascular grafts prepared using digital light processing 3D printing

The leading cause of death worldwide and a significant factor in decreased quality of life are the cardiovascular diseases. Endovascular operations like angioplasty, stent placement, or atherectomy are often used in vascular surgery to either dilate a narrowed blood artery or remove a blockage. As an alternative, a vascular transplant may be utilised to replace or bypass a dysfunctional or blocked blood vessel. Despite the advancements in endovascular surgery and its popularisation over the past few decades, vascular bypass grafting remains prevalent and is considered the best option for patients in need of long-term revascularisation treatments. Consequently, the demand for synthetic vascular grafts composed of biocompatible materials persists. To address this need, biodegradable clopidogrel (CLOP)-loaded vascular grafts have been fabricated using the digital light processing (DLP) 3D printing technique. A mixture of polylactic acid-polyurethane acrylate (PLA-PUA), low molecular weight polycaprolactone (L-PCL), and CLOP was used to achieve the required mechanical and biological properties for vascular grafts. The 3D printing technology provides precise detail in terms of shape and size, which lead to the fabrication of customised vascular grafts. The fabricated vascular grafts were fully characterised using different techniques, and finally, the drug release was evaluated. Results suggested that the performed 3D-printed small-diameter vascular grafts containing the highest CLOP cargo (20% w/w) were able to provide a sustained drug release for up to 27 days. Furthermore, all the CLOP-loaded 3D-printed materials resulted in a substantial reduction of the platelet deposition across their surface compared to the blank materials containing no drug. Haemolysis percentage for all the 3D-printed samples was lower than 5%. Moreover, 3D-printed materials were able to provide a supportive environment for cellular attachment, viability, and growth. A substantial increase in cell growth was detected between the blank and drug-loaded grafts.Graphical

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.

Hydrogen sulfide releasing and carboxybetaine modified vascular graft with enhanced anticoagulant, anticalcification, and pro-endothelialization properties

In the cardiovascular system, hydrogen sulfide(H2S) gasotransmitter regulates physiological processes involved in vasorelaxation, cardioprotection, anti-inflammation, and anti-oxidation. In this study, H2S releasing and carboxybetaine modified vascular graft with enhanced anticoagulant, anticalcification, and pro-endothelialization properties was designed and fabricated to meet the demand for small-diameter vascular grafts. Initially, a keratin-based bio-macromolecular donor of H2S was synthesized and then coelectrospun with polycaprolactone(PCL) to afford nanofibrous mats. Next, zwitterionic carboxybetaine was immobilized through dopamine self-polymerization to prolong the release of H2S, improve blood compatibility, and reduce calcification effectively. The biocomposite mats performed cell selectivity by promoting the adhesion and migration of HUVECs while inhibiting the proliferation of HUASMCs. Furthermore, the mats showed an excellent ability to resist oxidative stress. The results of the 3D perfusion culture proved that the grafts could promote endothelium formation under shear force. In vivo implantation results suggested that these grafts were capable of facilitating rapid endothelialization and reducing calcification.