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Synergetic coordination and catecholamine chemistry for catalytic generation of nitric oxide on vascular stents

机译:协同配位和儿茶酚胺化学在血管支架上催化生成一氧化氮

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摘要

The unique advantages of nitric oxide (NO) in cardiovascular disease therapy have driven the development of methods to functionalize cardiovascular stents for local generation of NO. However, current NO-generating materials used for surface engineering stents have limitations such as a complex fabrication process, poor stent adhesion strength, and low control of NO release. Herein, we apply synergetic coordination and catecholamine surface chemistry to develop an adhesive NO-generating coating with a copper-catecholamine framework through a simple, one-step molecule/ion co-assembly process. The copper-catecholic-selenocystamine framework provides glutathione peroxidase (GPx)-like interfacial catalytic activity, which results in long-term, stable, adjustable NO release rates from the coating. The resulting desirable therapeutic dose and release kinetics of NO endow the vascular stent with the ability to simultaneously inhibit platelet activation and smooth muscle cell (SMC) proliferation, and enhances endothelial cell (EC) adhesion, proliferation, and migration in vitro. Vascular stent functionalized by the optimized copper-catecholic-selenocystamine coating significantly suppresses thrombosis, promotes re-endothelialization, and reduces intimal hyperplasia in vivo, and may be promising to address the clinical complications associated with restenosis and late stent thrombosis.
机译:一氧化氮(NO)在心血管疾病治疗中的独特优势推动了功能化心血管支架局部生成NO的方法的发展。然而,当前用于表面工程支架的NO生成材料具有局限性,例如复杂的制造过程,差的支架粘附强度以及对NO释放的低控制。在本文中,我们应用协同配位和儿茶酚胺表面化学,通过简单的一步式分子/离子共组装过程,开发出具有铜-儿茶酚胺骨架的胶粘剂生成NO的涂层。铜-儿茶酚-硒代半胱胺骨架可提供类似谷胱甘肽过氧化物酶(GPx)的界面催化活性,从而可长期,稳定地调节涂料中的NO释放速率。所产生的理想的NO的治疗剂量和释放动力学赋予血管支架同时抑制血小板活化和平滑肌细胞(SMC)增殖的能力,并增强了内皮细胞(EC)的体外粘附,增殖和迁移能力。通过优化的铜-邻苯二酚-硒代半胱胺涂层功能化的血管支架可在体内显着抑制血栓形成,促进内皮再形成并减少内膜增生,并且可能有望解决与再狭窄和晚期支架血栓形成相关的临床并发症。

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