A self-sacrificing anti-inflammatory coating promotes simultaneous cardiovascular repair and reendothelialization of implanted devices

Abstract

During interventional surgeries of implantable cardiovascular devices in addressing cardiovascular diseases (CVD), the inevitable tissue damage will trigger host inflammation and vascular lumen injury, leading to delayed re-endothelization and intimal hyperplasia. Endowing cardiovascular implants with anti-inflammatory and endothelialization functions is conducive to the target site, offering significant tissue repair and regeneration benefits. Herein, inspired by the snake's molting process, a ShedWise device was developed by using the poly(propylene fumarate) polyurethane (PPFU) as the foundational material, which was clicked with hyperbranched polylysine (HBPL) and followed by conjugation with pro-endothelial functional Arg-Glu-Asp-Val peptide (REDV), and finally coated with a “self-sacrificing” layer having reactive oxygen species (ROS)-scavenging ability and degradability. During the acute inflammation in the initial stage of implantation, the ROS-responsive hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol (HBPAK) coating effectively modulated the level of environmental inflammation and resisted initial protein adsorption, showcasing robust tissue protection. As the coating gradually “sacrificed”, the exposed hyperbranched HBPL-REDV layer recruited specifically endothelial cells and promoted surface endothelialization. In a rat vascular injury model, the ShedWise demonstrated remarkable efficiency in reducing vascular restenosis, protecting the injured tissue, and fostering re-endothelization of the target site. This innovative design will introduce a novel strategy for surface engineering of cardiovascular implants and other medical devices.