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

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). <i>In vitro</i>, 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) <i>in vivo</i>. 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.