A small diameter bioactive prosthetic vascular graft with activated protein C (546.9)

Abstract

To date, there are no small (less than 5 mm) internal diameter vascular grafts that are FDA approved for clinical use due to high failure rates from thrombosis and increased cell proliferation, conditions that may be improved with use of enhanced bioengineered graft materials. Here we show that long term graft viability and patency can be improved by covalently binding activated protein C (APC) to prosthetic vascular graft surfaces due to APC’s inherent physical properties. Electrospun polyester (Dacron) grafts covalently bound with APC and woven plain Dacron prosthetic graft controls were evaluated in‐vivo in a common carotid artery bypass canine model with and without Plavix treatment. Blood work samples were taken from each canine (n=12) at 14, 30, 44 or 60 days after graft implantation. Explanted grafts were examined macroscopically and histologically. Upon comparison of all time points, APC grafts offered 25‐50% improvement in patency compared to control grafts. Plavix treatment increased patency of APC grafts from 50% to 100% over 60 days, while the control grafts showed no significant improvement in patency with Plavix treatment. Furthermore, histological evaluation showed that APC grafts had partial endothelial cell (EC) coverage of the luminal surface (CD31 positive) in the midd‐portion while the Dacron control grafts did not. At the anastomosis, there were no distinct differences in overall graft healing (SMC‐a, Ki67). Our results suggest that Dacron‐APC grafts not only offer a significant improvement in patency over woven control grafts, but also promote EC healing throughout the luminal surface of the graft. Perhaps longer term studies are needed to asses if partial EC coverage could become complete over time.Grant Funding Source: NIH‐803IR Phase II Grant.