Polyphenol-mediated sandwich-like coating promotes endothelialization and vascular healing

Drug-eluting stents have become one of the most effective methods to treat cardiovascular diseases. However, this therapeutic strategy may lead to thrombosis, stent restenosis, and intimal hyperplasia and prevent re-endothelialization. In this study, we selected 3-aminophenylboronic acid-modified hyaluronic acid and carboxylate chitosan as polyelectrolyte layers and embedded an epigallocatechin-3-gallate–tanshinone IIA sulfonic sodium (EGCG–TSS) complex to develop a sandwich-like layer-by-layer coating. The introduction of a functional molecular EGCG–TSS complex improved not only the biocompatibility of the coating but also its stability by enriching the interaction between the polyelectrolyte coatings through electrostatic interactions, hydrogen bonding, π–π stacking, and covalent bonding. We further elucidated the effectiveness of sandwich-like coatings in regulating the inflammatory response, smooth muscle cell growth behavior, stent thrombosis and restenosis suppression, and vessel re-endothelialization acceleration via in vivo and in vitro. Conclusively, we demonstrated that sandwich-like coating assisted by an EGCG–TSS complex may be an effective surface modification strategy for cardiovascular therapeutic applications.