Anti-fouling coating with ROS-Triggered On-Demand regulation of inflammation to favor tissue healing on vascular devices

Abstract

Unhealthy vascular tissue healing after stenting is primarily triggered by endothelial dysfunction and excessive smooth muscle cell proliferation, which is induced and aggravated by local thrombosis and excessive inflammation. Excessive inflammatory response is closely related to elevated concentrations of reactive oxygen species (ROS). Here, an environment-friendly coating strategy termed “Anti-fouling plus” with inflammatory self-regulation ability was proposed. Upon this, membrane-mimicking copolymer MA(PCLA) served as the antifouling coating, effectively inhibiting coagulation and inflammation during the early stage of implantation. Furthermore, a ROS-responsive prodrug was drawn into the coating to promote tissue healing. A molecular prodrug of thioketal-bearing dexamethasone was engineered to be released in a controlled and responsive manner in response to externally high levels of ROS. The released dexamethasone exhibited highly effective anti-inflammation properties after implantation. The combination of ROS-responsive prodrug and membrane-mimicking antifouling interface strategy intelligently integrated inflammation responsiveness and regulation, which could mediate a gentle vascular microenvironment and thus promote vascular remodeling. In vivo stent implantation studies demonstrated that the proposed “Anti-fouling plus” coating effectively inhibited neointima hyperplasia, modulated the inflammatory response and promoted endothelialization, offering promising surface modification approaches for vascular stents.