Rapid in situ endothelialization of a small diameter vascular graft with catalytic nitric oxide generation and promoted endothelial cell adhesion

Abstract

Thrombosis and neointimal hyperplasia are the main causes for the failure of small diameter vascular grafts, and a complete and functional endothelium is essential in preventing these problems. Therefore, grafts that could be endothelialized rapidly are highly desirable. This study constructed a vascular graft with catalytic nitric oxide (NO) generation and promoted endothelial cell (EC) adhesion for rapid in situ endothelialization, and examined the in vivo performance of an NO-generating vascular graft for the first time. A macroporous electrospun polycaprolactone (PCL) graft was prepared and modified via layer-by-layer self-assembly. Organoselenium immobilized polyethyleneimine was loaded onto the graft for in situ catalytic NO generation, while hyaluronic acid was grafted with an EC specific peptide Arg–Glu–Asp–Val and deposited to promote EC adhesion. This dual-modified material generated a strong and sustained flow of NO from S-nitrosoglutathione and significantly enhanced EC adhesion in vitro. In a co-culture experiment of ECs and smooth muscle cells (SMCs), this material promoted the adhesion of ECs and increased the EC/SMC ratio. After implantation in rats, the modified grafts showed a remarkably promoted endothelialization compared to PCL ones with an endothelium coverage of 89% versus 55% after 4 weeks, and the ECs on modified grafts were better organized in a pattern similar to that of the native vessel. The results indicated that the combination of catalytic NO generation and promoted EC adhesion proposed in this work may be a promising method for rapid endothelialization of small diameter vascular grafts.