Bioinspired NO release coating enhances endothelial cells and inhibits smooth muscle cells

Thrombus and restenosis after stent implantation are the major complications because of traditional drugs such as rapamycin delay the process of endothelialization. Nitric oxide (NO) is mainly produced by endothelial nitric oxide synthase (eNOS) on the membrane of endothelial cells (ECs) in cardiovascular system and plays an important role in vasomotor function. It strongly inhibits the proliferation of smooth muscle cells (SMCs) and ameliorate endothelial function when ECs were hurt. Inspired by this, introduce NO to traditional stent coating may alleviate endothelial insufficiency caused by rapamycin. Here we bring SNAP as the NO donor, mimicking how NO effect in vivo, into rapamycin coating to alleviate endothelial damage while inhibiting SMC's proliferation. SNAP was wicking to a hierarchical coating which had an upper porous layer and a dense polymer layer with rapamycin at bottom. Cells were cultured on the coatings and observed that the injure of ECs had been restoring while the growth of SMCs were further diminishing. Genome analysis was detected to further clarify possible signaling pathways: the effect of cell growth attenuated by NO may cause by affecting cell cycle and enhancing inflammation. These findings supported the idea that introducing NO to traditional drug-eluting stents alleviates incomplete endothelialization and further inhibit the stenosis caused by SMCs’ proliferation.