Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Current vascular access options require frequent interventions. In situ tissue engineering may overcome these limitations by combining the initial success of synthetic grafts with the long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds(6mm-Ø) made of supramolecular polycarbonate-bisurea(PC-BU), with a polycaprolactone(PCL) anti-kinking-coil, were implanted between the carotid artery and jugular vein in goats. A subset was bio-functionalized using bisurea-modified-SDF1α-derived peptides and ePTFE grafts as controls. Patency was monitored monthly. Grafts were explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold was resorbed and replaced by, and vascular neo-tissue, including elastin, contractile markers an endothelial lining. No dilations, ruptures, or aneurysms were observed and grafts were successfully cannulated at termination. SDF1α-peptide-biofunctionalization did not influence outcomes. Patency was lower in the TE grafts(50%) compared to controls(100% patency), predominantly caused by intimal hyperplasia. We demonstrated the rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula in a large animal model. Despite lower patency compared to ePTFE, this transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages. This article is protected by copyright. All rights reserved.