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接枝两亲性聚合物刷的冠状动脉支架用于抗凝血和内皮化。

Bifunctional polymer brush-grafted coronary stent for anticoagulation and endothelialization.

机构信息

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.

Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111725. doi: 10.1016/j.msec.2020.111725. Epub 2020 Nov 14.

Abstract

At present, cardiovascular stent intervention faces clinical complications such as delayed endothelialization, late thrombosis and restenosis after implantation. In this work, a kind of bifunctional polymer brush-grafted coronary stent with anticoagulant and endothelial functions was developed. First, a block copolymer brush with zwitterionic structure consisting of sulfoethyl methacrylate (SBMA) and glycidyl methacrylate (GMA) was surface-induced grafted onto the surface of bare metal coronary stent by atom transfer radical polymerization. The diethylenetriamine NONOate (DETA NONOate), acted as nitric oxide (NO) donor to promote endothelialization, was then attached to polyglycidyl methacrylate (PGMA) brush by a reactive epoxy group to produce NO. The process of chemical modification and the release behavior of NO were characterized in detail. Moreover, the results of anticoagulant test, cytotoxicity test, endothelial cells (ECs) proliferation test and animal experiment of this bifunctional polymer brush-grafted coronary stent we proposed indicate that the zwitterion modified and NO supplied bifunctional coatings has good anticoagulant property, no cytotoxicity and significant endothelialization effect. This work opens the door to combine biological activity of NO and anticoagulant effect of zwitterions, which has great potential to address post-operative side effects associated with restenosis and late stent thrombosis.

摘要

目前,心血管支架介入面临着一些临床并发症,如植入后内皮化延迟、晚期血栓形成和再狭窄。在这项工作中,开发了一种具有抗凝和内皮功能的双功能聚合物刷修饰的冠状动脉支架。首先,通过原子转移自由基聚合,将由磺基乙基甲基丙烯酸酯(SBMA)和甲基丙烯酸缩水甘油酯(GMA)组成的具有两性离子结构的嵌段共聚物刷接枝到裸金属冠状动脉支架表面。然后,通过反应性环氧基团将作为一氧化氮(NO)供体以促进内皮化的二亚乙基三胺 NONO 盐(DETA NONO 盐)连接到聚甲基丙烯酸缩水甘油酯(PGMA)刷上以产生 NO。详细表征了化学修饰过程和 NO 的释放行为。此外,我们提出的这种双功能聚合物刷修饰的冠状动脉支架的抗凝试验、细胞毒性试验、内皮细胞(EC)增殖试验和动物实验结果表明,两性离子改性和提供 NO 的双功能涂层具有良好的抗凝性能、无细胞毒性和显著的内皮化作用。这项工作为结合 NO 的生物活性和两性离子的抗凝效果开辟了道路,这对于解决与再狭窄和晚期支架内血栓形成相关的术后副作用具有很大的潜力。

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