Engineering Immunomodulatory Stents Using a Biomimetic Nanozyme System for Vascular Healing.

Delayed endothelialization and inflammatory response are two major obstacles that hinder vascular healing by drug-eluting stents (DES). Here, we report a biomimetic nanozyme strategy to address this issue. We first design and anchor a robust glutathione peroxidase (GPx)-biomimetic nanozyme with diselenide-polyphenol networks on a stent. Then, a thrombin inhibitor, bivalirudin, is efficiently loaded onto the nanozyme utilizing its reversible interactions with polyphenol. The nanozymes exhibit potent GPx activity to controllably generate nitric oxide (NO) and on-demand elution of bivalirudin. The synergistic effects of NO and bivalirudin effectively inhibit thrombin activity, prevent platelet activation, and consequently suppress thrombosis as well as the inflammatory response associated with it. In vitro pathological model cell studies demonstrate that the nanozyme-engineered stents specifically inhibit smooth muscle cell (SMC) proliferation, regulate macrophage polarization, and promote the repair and proliferation of endothelial cells. Thus, it enables rapid endothelialization and vascular healing, preventing restenosis in rabbit and swine models.