Synergistic fusion of CD47, VE-cadherin and mussel adhesion protein promotes endothelialization and suppresses inflammation in vascular stents

作者：Wenhua Yan, Shuyu Li, Tian Zhang, Junli Huang, Chengchen Deng, Kunshan Yuan, Nan Huang, Haijun Zhang, Guixue Wang · 发表于：Bioactive Materials · 年份：2025 · DOI：10.1016/j.bioactmat.2025.09.015 · 被引用次数：7 · 研究领域：Phagocytosis and Immune Regulation、Cell Adhesion Molecules Research、Extracellular vesicles in disease

Endothelial cell (EC)-specific coatings for vascular stents are crucial for enhancing their biocompatibility and preventing complications such as restenosis and thrombosis. This study developed an innovative CD47-VE-cadherin-Mfp5 (CD47-VE-M) fusion protein coating for cardiovascular stents that integrates three distinct functional domains: endothelial adhesion enhancement (VE-cadherin EC1-2), macrophage inhibitory signaling (CD47), and substrate adhesion reinforcement (Mfp5). In vitro , CD47-VE-M coatings significantly promoted EC adhesion (3.4-fold increase vs. bare-metal stent (BMS) (p < 0.001)), directional migration (accelerated 62 % compared to BMS at 24 h) and proliferation (2.3-fold increase vs. BMS (p < 0.01)), with increased VE-cadherin expression and improved tight junction formation (1.5-fold higher than BMS (p < 0.001)). Additionally, the CD47-VE-M coating reduced macrophage phagocytosis by 59 % (p < 0.01). Compared with BMS, synergistic CD47-VE-M fusion protein-coated stents showed accelerated endothelialization and reduced neointimal hyperplasia and restenosis by 64.4 % (p < 0.001) in vivo . Besides, the coating also decreased the presence of M1 pro-inflammatory macrophages (64.74 % decrease vs. BMS (p < 0.01)), which mitigated the inflammatory response. This novel coating strategy overcomes the limitations of current drug-eluting stent (DES) by simultaneously enhancing endothelial regeneration and suppressing pathological inflammation. Synergistic integration o...