LOX-1-Based Assembly Layer on Devices Surface to Promote Endothelial Repair and Reduce Complications for In Situ...

Rapid endothelialization and functional recovery are considered as promising methods to extend the long-term effectiveness of cardiovascular implant materials. LOX-1 participates in the initiation and development of atherosclerosis and is highly expressed in a variety of cells involved in atherosclerosis, hence it is feasible to accelerate the recovery of endothelial function and inhibit the development of existing plaques by regulating LOX-1. Herein, the surface is modified with Poly I, a LOX-1 inhibitor, using rich amino dendritic macromolecules (PAMAM) as the linker coating, to against the pathological microenvironment. Poly I modified surface resisted endothelial damage caused by oxidative stress through the LOX-1-NADPH signaling pathway and inhibited endothelial inflammation via the LOX-1-NF-κB signaling pathway. It also promoted endothelial cell migration and inhibited platelet adhesion. Moreover, the Poly I modified surface can inhibit oxLDL-induced macrophage foam cell formation and alleviate inflammation by modulating macrophage phenotypes. Poly I modified surface significantly reduced plaque burden after treatment of atherosclerotic model rats, most importantly, it significantly inhibited post-implantation-induced restenosis and thrombosis. In vivo and in vitro evaluations confirmed its safety and therapeutic efficacy against atherosclerosis. Overall, the multifunctional Poly I with pathological microenvironment regulation exhibits potential application value in the surface engineering of cardiovascular devices.