Self-assembled, carrier-free cyclic chemerin 9/tannic acid coating for enhanced vascular healing following stent deployment.

Abstract

Endovascular stent implantation has gained traction as a critical therapeutic strategy for managing cerebral atherosclerotic stenosis and preventing acute ischaemic stroke. Although bare-metal stents (BMSs) are widely used in clinical applications, their therapeutic efficacy is limited by in-stent restenosis (ISR). Drug-eluting stents (DESs) have been developed to inhibit ISR and have demonstrated satisfactory short-term clinical results. However, the non-specific cytotoxicity of the eluted drugs on endothelial cells impairs re-endothelialisation, thereby increasing the risk of ISR and stent thrombosis at a late stage. In addition, the residual polymer carriers and coupling agents can induce persistent hypersensitivity reactions and inflammation. Herein, we developed an anti-inflammatory, endothelium-compatible stent. The tannic acid (TA)/cyclic chemerin 9 (C9)-modified stent was fabricated via a layer-by-layer (LBL) self-assembly method, leveraging noncovalent interactions between the anti-inflammatory peptide cyclic C9 and polyphenol TA. This stent was constructed without polymer carriers or coupling agents. The TA and C9 released from the TA/C9-modified stent synergistically attenuated inflammatory cascades and repressed smooth muscle cell proliferation and migration, and exerted no adverse effect on endothelial cell coverage. This design effectively eliminates chronic inflammation associated with residual carriers and coupling agents. In a porcine model, the TA/C9-modified stent demonstrated superior efficacy in enhancing vascular healing and suppressing neointimal hyperplasia. These results indicate that the TA/C9-modified stent represents a promising strategy for improving long-term outcomes in cerebrovascular stent design.