Epsin mimetic UPI Peptide Delivery Strategies to Improve Endothelization of Vascular Grafts.

Endothelialization of engineered vascular grafts for replacement of small-diameter coronary arteries remains a critical challenge. The ability for an acellular vascular graft to promote endothelial cell (EC) recruitment in the body would be very beneficial. This study investigated epsins as a target since they are involved in internalization of vascular endothelial growth factor receptor 2. Specifically, epsin-mimetic UPI peptides were delivered locally from vascular grafts to block epsin activity and promote endothelialization. The peptide delivery from fibrin coatings allowed for controlled loading and provided a significant improvement in EC attachment, migration, and growth in vitro. The peptides had even more important impacts after grafting into rat abdominal aortae. The peptides prevented graft thrombosis and failure that was observed with a fibrin coating alone. They also modulated the in vivo remodeling. The grafts were able to remodel without the formation of a thick fibrous capsule on the adventitia with the 100 µg/mL peptide-loaded condition, and this condition enabled the formation of a functional EC monolayer in the graft lumen after only 1 week. Overall, this study demonstrated that the local delivery of UPI peptides is a promising strategy to improve the performance of vascular grafts. This article is protected by copyright. All rights reserved.