Surface mediated gene delivery for in situ accelerating endothelialization of vascular graft

As an urgently needed device for vascular diseases, small-diameter vascular grafts have been usually used in clinic. But they are limited by high thrombogenicity in clinical application. Rapid endothelialization is a promising approach to construct antithrombogenic inner surface of the vascular graft. The main bottleneck for rapid endothelialization is the adhesion, migration and proliferation of endothelial cells (ECs) in situ of small-diameter vascular grafts.

Herein, we innovatively fabricated an intelligent gene delivery small-caliber vascular graft from electrospun nanofibrous graft of poly(lactic acid-co-caprolactone) and gelatin with the aim of rapid in situ endothelialization. The graft surface was co-modified with ECs adhesive peptide of Arg-Glu-Asp-Val (REDV) and responsive gene delivery system. REDV can selectively adhere ECs onto the graft surface, subsequently, and the overexpressed matrix metalloproteinase by ECs can effectively cleave the linker peptide GPQGIWGQ-C, finally, the gene complexes were intelligently and enzymatically released from graft surface, thereby the released gene can efficiently transfect ECs. Importantly, this enzymatically releasing gene surface has been proved to be safe and temporary stable in blood flow owing to biotin-avidin interaction to fix the gene complexes on the inner surface of vascular grafts through the GPQGIWGQ-C peptide linker. It has the advantage of specifically adhering ECs onto the surface and smartly transfecting them with high transfection efficiency. The co-modified surface extremely accelerated the luminal endothelialization in vivo, which might be attributed to the synergistic effect of REDV and effective gene transfection. Particularly, the intelligent and responsive gene release surface will open a new avenue to enhance the endothelialization of blood contacting devices.