A nitric oxide-eluting and REDV peptide-conjugated coating promotes vascular healing

Abstract

Drug-eluting stents (DESs) placement remarkably reduces the over-proliferation of smooth muscle cells (SMCs) and thus neointimal hyperplasia. However, the pharmacological agent also slows down the re-endothelization, delays injury vascular healing and increases the risk of in-stent restenosis (ISR). Here, inspired by mussel foot proteins (Mfps), a mimicking endothelium functional stent coating was efficiently fabricated by thiol-ene "click" reaction, consisting of catechol grafted chitosan (CS-C), zinc sulfate, and Arg-Glu-Asp-Val (REDV) peptide. The mimicking endothelium coating could continuously catalyze endogenous nitric oxide (NO) gas and maintain the bioactivity of REDV peptide. Compared with bare stents, the mimicking coatings significantly inhibited the acute thrombosis for the first 1-week, accelerated re-endothelization and decreased in-stent restenosis for 1- and 3-month after implantation. In addition, the synergistic effect of NO and REDV peptide also regulated inflammation response and promoted the expression of muscle fiber.

Keywords: Cardiovascular stents; Click reaction; Mimicking endothelial function; Mussel-inspired peptide mimic; Nitric oxide; REDV peptide.