Zhang Bo, Qin Yumei, Wang Yunbing
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.
Biomaterials. 2022 May;284:121478. doi: 10.1016/j.biomaterials.2022.121478. Epub 2022 Mar 28.
Drug-eluting stents (DESs) placement remarkably reduces the over-proliferation of smooth muscle cells (SMCs) and thus neointimal hyperplasia. However, the pharmacological agent also slows down the re-endothelization, delays injury vascular healing and increases the risk of in-stent restenosis (ISR). Here, inspired by mussel foot proteins (Mfps), a mimicking endothelium functional stent coating was efficiently fabricated by thiol-ene "click" reaction, consisting of catechol grafted chitosan (CS-C), zinc sulfate, and Arg-Glu-Asp-Val (REDV) peptide. The mimicking endothelium coating could continuously catalyze endogenous nitric oxide (NO) gas and maintain the bioactivity of REDV peptide. Compared with bare stents, the mimicking coatings significantly inhibited the acute thrombosis for the first 1-week, accelerated re-endothelization and decreased in-stent restenosis for 1- and 3-month after implantation. In addition, the synergistic effect of NO and REDV peptide also regulated inflammation response and promoted the expression of muscle fiber.
药物洗脱支架(DESs)的植入显著减少了平滑肌细胞(SMCs)的过度增殖,从而减少了新生内膜增生。然而,药物也会减缓再内皮化过程,延迟损伤血管愈合,并增加支架内再狭窄(ISR)的风险。在此,受贻贝足蛋白(Mfps)启发,通过硫醇-烯“点击”反应高效制备了一种模拟内皮功能的支架涂层,其由儿茶酚接枝壳聚糖(CS-C)、硫酸锌和精氨酸-谷氨酸-天冬氨酸-缬氨酸(REDV)肽组成。该模拟内皮涂层可持续催化内源性一氧化氮(NO)气体,并维持REDV肽的生物活性。与裸支架相比,模拟涂层在植入后的第1周显著抑制了急性血栓形成,加速了再内皮化,并在植入后1个月和3个月减少了支架内再狭窄。此外,NO和REDV肽的协同作用还调节了炎症反应并促进了肌纤维的表达。