The performance of cross-linked acellular arterial scaffolds as vascular grafts; pre-clinical testing in direct and isolation loop circulatory models

Abstract

There is a significant need for small diameter vascular grafts to be used in peripheral vascular surgery; however autologous grafts are not always available, synthetic grafts perform poorly and allografts and xenografts degenerate, dilate and calcify after implantation. We hypothesized that chemical stabilization of acellular xenogenic arteries would generate off-the-shelf grafts resistant to thrombosis, dilatation and calcification. To test this hypothesis, we decellularized porcine renal arteries, stabilized elastin with penta-galloyl glucose and collagen with carbodiimide / activated heparin and implanted them as transposition grafts in the abdominal aorta of rats as direct implants and separately as indirect, isolation-loop implants. All implants resulted in high patency and animal survival rates, ubiquitous encapsulation within a vascularized collagenous capsule, and exhibited lack of lumen thrombogenicity and no graft wall calcification. Peri-anastomotic neo-intimal tissue overgrowth was a normal occurrence in direct implants; however this reaction was circumvented in indirect implants. Notably, implantation of non-treated control scaffolds exhibited marked graft dilatation and elastin degeneration; however PGG significantly reduced elastin degradation and prevented aneurismal dilatation of vascular grafts. Overall these results point to the outstanding potential of crosslinked arterial scaffolds as small diameter vascular grafts.

Decellularized human placenta chorion matrix as a favorable source of small-diameter vascular grafts

“…In the US alone more than 1 million vascular grafts are needed in clinical practice every year [1]. Currently, autologous grafting from the patient's own arteries or veins is regarded as the gold standard for vascular tissue repair.…”

Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System

“…19 The surface cell coverage was identified as transanastomotic tissue overgrowth, which is a typical host reaction to cardiovascular implants. 20 Reviewing all data collected on implantation of acellular roots, Ingham and collaborators concluded recently that incomplete valve decellularization is associated with severe graft failure. 21 Other experimental approaches to building tissueengineered valves include use of cell-seeded biodegradable polymers (synthetic or fibrin-based, molded in the shape of an aortic valve root) to generate a homogeneous, isotropic collagenous structure lacking elastic fibers, before implantation, 22,23 implantation of stent-mounted acellular valves seeded with vascular fibroblasts or stem cells, 24 as well as use of polymers 22,25 and layered composites.…”

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

“…[63, 64] Strategies to stabilize ECM-based vascular grafts to prevent dilation include chemical crosslinking using carbodiimide chemistry to reduce ECM degradation[63] and perivascular polymer coating with electrospun PCL to prevent expansion. [65] However, stabilization of the ECM scaffold with either chemical crosslinking or polymer coating could also lead to increased stiffness and compliance mismatch between native arteries and vascular grafts and result in a severe inflammatory response and increased neointimal hyperplasia.…”