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.