A Polyphenol-Network-Mediated Coating Modulates Inflammation and Vascular Healing on Vascular Stents

Localized drug delivery from drug-eluting stents (DESs) to target sites provides therapeutic efficacy with minimal systemic toxicity. However, DESs failure may cause thrombosis, delay arterial healing, and impede re-endothelialization. Bivalirudin (BVLD) and nitric oxide (NO) promote arterial healing. Nevertheless, it is difficult to combine hydrophilic signal molecules with hydrophobic antiproliferative drugs while maintaining their bioactivity. Here, we fabricated a micro- to nanoscale network assembly consisting of copper ion and epigallocatechin gallate (EGCG) via π–π interactions, metal coordination, and oxidative polymerization. The network incorporated rapamycin and immobilized BVLD by the thiol–ene “click” reaction and provided sustained rapamycin and NO release. Unlike rapamycin-eluting stents, those coated with the EGCG-Cu-rapamycin-BVLD complex favored competitive endothelial cell (EC) growth over that of smooth muscle cells, exhibited long-term antithrombotic efficacy, and attenuated the negative impact of rapamycin on the EC. In vivo stent implantation demonstrated that the coating promoted endothelial regeneration and hindered restenosis. Therefore, the polyphenol-network-mediated surface chemistry can be an effective strategy for the engineering of multifunctional surfaces.