Small‐diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off‐the‐shelf small‐diameter vascular grafts for clinical applications remain a great ...limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(ε‐caprolactone) (PCL) sheaths are prepared by freeze‐thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)‐heparin/poly‐L‐lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL‐NFC/PVA‐NPs tubes) are investigated. The effect of compliance of PCL‐NFC/PVA‐NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL‐NFC/PVA‐NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL‐NFC/PVA‐NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL‐NFC/PVA‐NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small‐diameter vascular grafts.
Bilayer anticoagulant hydrogel tubes with poly(ε‐caprolactone) sheaths mimic the structures (layered structure and anticoagulant inner surface) and mechanical properties (excellent ductility, sufficient burst pressure, and good compliance) of the artery, which have excellent biocompatibility, good tissue compatibility, and good patency. Hydrogel tubes are great promising candidates for small‐diameter vascular grafts.
As a result of thrombosis or intimal hyperplasia, synthetic artificial vascular grafts had a low success rate when they were used to replace small-diameter arteries (inner diameter < 6 mm). C-type ...natriuretic peptides (CNP) have anti-thrombotic effects, and can promote endothelial cell (EC) proliferation and inhibit vascular smooth muscle cell (SMC) over-growth. In this study, poly(ε-caprolactone) (PCL) vascular grafts loaded with CNP (PCL-CNP) were constructed by electrospinning. The PCL-CNP grafts were able to continuously release CNP at least 25 days in vitro. The results of scanning electron microscopy (SEM) and mechanical testing showed that the loading of CNP did not change the microstructure and mechanical properties of the PCL grafts. In vitro blood compatibility analysis displayed that PCL-CNP grafts could inhibit thrombin activity and reduce platelet adhesion and activation. In vitro cell experiments demonstrated that PCL-CNP grafts activated ERK1/2 and Akt signaling in human umbilical vein endothelial cells (HUVECs), as well as increased cyclin D1 expression, enhanced proliferation and migration, and increased vascular endothelial growth factor (VEGF) secretion and nitric oxide (NO) production. The rabbit arteriovenous (AV)-shunt ex vitro indicated that CNP loading significantly improved the antithrombogenicity of PCL grafts. The assessment of vascular grafts in rat abdominal aorta implantation model displayed that PCL-CNP grafts promoted the regeneration of ECs and contractile SMCs, modulated macrophage polarization toward M2 phenotype, and enhanced extracellular matrix remodeling. These findings confirmed for the first time that loading CNP is an effective approach to improve the hemocompatibility and vascular regeneration of synthetic vascular grafts.
Small-diameter (< 6 mm) vascular grafts (SDVGs) have not been made clinically available due to their prevalence of thrombosis, limited endothelial regeneration and intimal hyperplasia. The incorporation of bioactive molecules into SDVGs serves as an effective solution to improve hemocompatibility and endothelialization. In this study, for the first time, we loaded C-type natriuretic peptides (CNP) into PCL grafts by electrospunning and confirmed the effectiveness of loading CNP on improving the hemocompatibility and vascular regeneration of artificial vascular grafts. Regenerative advantages included enhancement of endothelialization, modulation of macrophage polarization toward M2 phenotypes, and improved contractile smooth muscle cell regeneration. Our investigation brings attention to CNP as a valuable bioactive molecule for modifying cardiovascular biomaterial.
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Polyurethanes (PUs), formed by the reaction of diisocyanates with polyols (or equivalent) in the presence of a catalyst, have a wide variety of industrial uses. Much recent attention has focused on ...their biomedical applications, owing to their biocompatibility, biodegradability and tailorable chemical and physical forms. Examples of such application areas include antibacterial surfaces and catheters, drug delivery vehicles, stents, surgical dressings/pressure sensitive adhesives, tissue engineering scaffolds and electrospinning, nerve generation, cardiac patches and PU coatings for breast implants. Following a brief introduction to PUs, this review surveys selected articles, mostly from 2014 to 2017, that highlight this diverse range of biomedical applications offered by PU materials and coatings.
Rapid endothelialization is a key factor that determines the success of small-diameter vascular grafts as an artery substitute in the treatment of cardiovascular diseases. Aimed to facilitate ...vascular regeneration, we developed a vascular scaffold loaded with resveratrol, which is a natural compound extracted from plants and showed multifaceted effects in cardiovascular protection. The tubular poly(ε-caprolactone) (PCL) scaffold was prepared by electrospinning with resveratrol in the PCL solution. In vitro assay demonstrated that resveratrol could be released from the scaffolds in a sustained and controlled manner. Cell culture results indicated that the migration of endothelial cells (ECs), nitric oxide production, and the ability of tube formation increased in the resveratrol-containing PCL scaffold groups compared with the PCL control. Meanwhile, the level of tumor necrosis factor (TNF)-α, the main proinflammatory factor secreted from macrophages, was reduced, and the messenger RNA expressions of the M2 macrophage-related genes were increased in the resveratrol-containing group. Further, in vivo implantation was performed by replacing rat abdominal aorta. We observed fast endothelialization and enhanced vascular regeneration in rats with resveratrol-containing scaffolds. The presence of resveratrol also induced a large number of M2 macrophages to infiltrate into the graft wall. Taken together, the incorporation of resveratrol into the PCL grafts enhanced the vascular regeneration by modulation of ECs and macrophages.
Endothelial cell (EC) models have evolved as important tools in biomaterial research due to ubiquitously occurring interactions between implanted materials and the endothelium. However, screening the ...available literature has revealed a gap between material scientists and physiologists in terms of their understanding of these biomaterial–endothelium interactions and their relative importance. Consequently, EC models are often applied in nonphysiological experimental setups, or too extensive conclusions are drawn from their results. The question arises whether this might be one reason why, among the many potential biomaterials, only a few have found their way into the clinic. In this review, we provide an overview of established EC models and possible selection criteria to enable researchers to determine the most reliable and relevant EC model to use.
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.
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Cell‐free polymeric tissue‐engineered vascular grafts (TEVGs) have shown great promise towards clinical translation; however, their limited bioactivity and remodeling ability challenge this cause. ...Here, a novel cell‐free bioresorbable small diameter silk TEVG system functionalized with decellularized human Wharton's jelly (dWJ) matrix is developed and successfully implanted as interposition grafts into rabbit jugular vein. Implanted TEVGs remain patent for two months and integrate with host tissue, demonstrating neo‐tissue formation and constructive remodeling. Mechanistic analysis reveals that dWJ matrix is a reservoir of various immunomodulatory cytokines (Interleukin‐8, 6, 10, 4 and tumor necrosis factor alpha (TNF‐α)), which aids in upregulating M2 macrophage‐associated genes facilitating pro‐remodeling behavior. Besides, dWJ treatment to human endothelial cells upregulates the expression of functional genes (cluster of differentiation 31 (CD31), endothelial nitric oxide synthase (eNOS), and vascular endothelial (VE)‐cadherin), enables faster cell migration, and elevates nitric oxide (NO) production leading to the in situ development of endothelium. The dWJ functionalized silk TEVGs support increased host cell recruitment than control, including macrophages and vascular cells. It endows superior graft remodeling in terms of a dense medial layer comprising smooth muscle cells and elevates the production of extracellular matrix proteins (collagen and elastin). Altogether, these findings suggest that dWJ functionalization imitates the usefulness of cell seeding and enables graft remodeling.
Minimal bioactivity of acellular polymeric tissue‐engineered vascular grafts (TEVG) limits their chances of clinical translation. In this regard, a next‐generation acellular silk‐based TEVG is prepared and functionalized with human Wharton's jelly matrix. It caters biological activity and precludes the possibility of graft failure by modulating the host immune response.
There is a tremendous clinical need for synthetic vascular grafts either for bypass procedure or vascular access during hemodialysis. However, currently, there is no small-diameter vascular graft ...commercially available to meet long-term patency requirement due to frequent thrombus formation and intimal hyperplasia. This chapter describes the fabrication of electrospun small-diameter polycarbonate-urethane (PCU) vascular graft with a biomimetic fibrous structure. Additionally, the surface of the vascular graft is aminated via plasma treatment for the subsequently end-point heparin immobilization to enhance antithrombosis property.
•Fabrication of triple-layered vascular grafts that mimic native blood vessels.•Graft compliance is regulable and compatible with sheep carotid artery.•Triple-layered vascular grafts are promising as ...small-diameter vessel replacements.
There is an urgent clinical for small diameter vascular grafts (SDVGs) for use in the treatment of coronary artery disease. Moreover, biodegradable SDVGs are drawing increasing attention because they have the potential to restore vascular function with the degradation of vascular graft and tissue regeneration. In this study, we designed triple-layered SDVGs to mimic the native arterial structure, with each layer contributing its unique porosity to the porous structure. We evaluated triple-layered SDVGs in a sheep carotid arterial replacement model. After implantation for 12 months, two grafts were patent and indicated the feasibility of using grafts in large animals. Nevertheless, it was determined that both grafts formed aneurysms at the proximal end. The prevention of such aneurysms remains a challenge for future investigation.
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Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant ...technological advances have generated small‐diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood‐contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood‐contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells and the quiescence of smooth muscle cells are critical to the maintenance of patency. Several strategies to modify blood‐contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin.
Developing a biocompatible blood‐contacting surface remains a major challenge for tissue engineered vascular grafts (TEVGs). This paper reviews the current state of TEVGs with an emphasis on the blood‐contacting surface, which includes general vascular physiology and developmental challenges, materials currently employed in TEVGs, and strategies to modify blood‐contacting surfaces to resist thrombosis and control cellular recruitment.
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