One-pot deposition of a multi-functional biomimetic coating for vascular stents

Abstract

Implantation of vascular stents, with particular reference to drug-eluting stents (DESs), is considered the main tool in treating coronary artery diseases (CADs) and has saved millions of lives. However, the complications, in-stent thrombosis (IST) and in-stent restenosis (ISR), of DESs are a major risk for stenting failure because of thrombus and hyperplasia. Vascular endothelial cells (ECs) are capable of secreting extracellular matrix (ECM) and vasoactive substances to maintain and regulate the homeostasis of the vascular environment. Hence, conferring endothelial-like functions to vascular stents is an effective solution to improve their biocompatibility. In this work, we propose a simple preparation method for a multi-functional coating that can mimic ECs function with continuous generation of nitric oxide (NO), located in a hyaluronic acid platform. The coating was fabricated by a one-pot deposition of dopamine (DA), thiol-hyaluronic acid (HA-SH), and copper ions (Cu). Thiol-modified HA was efficiently incorporated by DA, which mimics the adhesion mechanism of mussels, via the “thiol-Michael addition” click reaction, along with the complexing Cu which can catalyze the endogenous S-nitrosothiols (RSNO) to continuous liberation nitric oxide (NO). Both in vitro and in vivo experiments showed that the biomimetic microenvironment which hyaluronic acid coating combined with NO-generation capability could remarkably improve the anticoagulant properties of the vascular stents and further accelerate the in-situ endothelialization process while inhibiting the intimal hyperplasia and regulating inflammation. In conclusion, this study shows a simple one-pot method for the construction of multi-functional coatings that mimic an endothelial-like environment, which might endow vascular stents with enhanced anti-coagulation and endothelialization capability to prevent IST and ISR.