The Tissue-Engineered Vascular Graft—Past, Present, and Future

Abstract

Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented.

Enhanced Vascular Biocompatibility and Remodeling of Decellularized and Secured Xenogeneic/Allogeneic Matrices in a Porcine Model

“…These results are encouraging, and a longer follow-up will indicate new vessels’ long-term permeability essentially dependent on intimal hyperplasia evolution. This is obviously crucial, and some authors recommend decellularized matrices in vitro endothelial cell seeding before implantation to improve patency rate [19, 30, 31]. In a previous work, seeded DHFL with stem cells for parietal reconstructions were quickly obtained, confirming the absence of treatment cytotoxicity [32].…”

“…However, prosthesis recellularization, which is of major concern regarding vessel regeneration for growth, viability potential, and mechanical stability, was different between tissues [12]. For this aspect, DPPt and DHP showed the best results, while DHFL and GBP showed similar results as synthetic grafts without viability and growth potential, prone to calcifications, aneurysm formation, and unable to fight against infection [19, 20]. …”

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

“…[26, 27] Since acute thrombosis and progressive development of intimal hyperplasia are primary causes of low patency rates for prosthetic grafts, much effort has been put into improving hemocompatibility and compliance of vascular grafts. In our previous work, we developed several strategies to immobilize heparin onto decellularized ECM-based vascular grafts to reduce thrombosis, while preserving mechanocompatibility that led to a corresponding reduction in intimal hyperplasia.…”

Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study

“…Both approaches displayed some promising results in vitro , in vivo , and even in several case studies and ongoing clinical trials; however, neither has of yet been translated into wide clinical applications. 1,3,4 For instance, despite the great promise of cell sheet-based self-assembly techniques, their production process is labor-intensive, requires costly bioreactor work, and involves long in vitro manipulation periods (typically >12 weeks). 1,3 …”

“…1,3,4 These scaffolds may represent a compromise between traditional in vitro and more advanced in situ tissue engineering, in that they can not only be preconditioned in a bioreactor in vitro but also be intrinsically bioactive in vivo in recruiting an adequate host cell regenerative response following implantation. 6 Major issues of concern, though, relate to their ability to maintain graft patency, flexibility, and contractility following implantation.…”