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通过支架内再狭窄大鼠模型评估一种促进愈合的聚多巴胺涂层支架。

evaluation of a pro-healing polydopamine coated stent through an in-stent restenosis rat model.

作者信息

Hertault Adrien, Chai Feng, Maton Mickael, Sobocinski Jonathan, Woisel Patrice, Maurel Blandine, Lyskawa Joël, Blanchemain Nicolas

机构信息

Univ. Lille, INSERM, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.

出版信息

Biomater Sci. 2021 Jan 5;9(1):212-220. doi: 10.1039/d0bm01204a.

Abstract

Drug-eluting stents have demonstrated efficiency in in-stent restenosis (ISR) but induced a risk of late acute thrombosis by delaying strut re-endothelialization. Polydopamine (PDA), a biocompatible polymer inspired from adhesive proteins of mussels, has been reported to promote endothelial cell (EC) proliferation while limiting SMC proliferation in vitro, thus suggesting the pro-healing potential. This study aimed at evaluating in vivo the impact of the pro-healing PDA-coated stent on ISR and on the quality of the strut re-endothelialization in a rat model. PDA-coated stents demonstrated a significant reduction in ISR in vivo compared to bare metal stents (ratio neointima/media = 0.48 (±0.26) versus 0.83 (±0.42), p < 0.001). Western blot analyses identified a trend towards an increased activation of p38 MAPK phosphorylation and its anti-proliferative effects on vascular SMC that could explain the results observed in morphological analyses. This bioinspired and biocompatible polydopamine layer could intrinsically limit ISR. In addition, according to its latent reactivity, PDA offers the possibility to immobilize some relevant drugs on the PDA-functionalized stent to provide potential synergistic effects.

摘要

药物洗脱支架已在支架内再狭窄(ISR)方面显示出有效性,但由于延迟了支架小梁的再内皮化,会引发晚期急性血栓形成的风险。聚多巴胺(PDA)是一种受贻贝粘附蛋白启发的生物相容性聚合物,据报道它在体外可促进内皮细胞(EC)增殖,同时限制平滑肌细胞(SMC)增殖,因此显示出促进愈合的潜力。本研究旨在在大鼠模型中体内评估具有促进愈合作用的PDA涂层支架对ISR以及支架小梁再内皮化质量的影响。与裸金属支架相比,PDA涂层支架在体内显示出ISR显著降低(新生内膜/中膜比值=0.48(±0.26)对0.83(±0.42),p<0.001)。蛋白质免疫印迹分析发现p38丝裂原活化蛋白激酶(MAPK)磷酸化激活增加及其对血管SMC的抗增殖作用有增加的趋势,这可以解释形态学分析中观察到的结果。这种受生物启发且具有生物相容性的聚多巴胺层可能内在地限制ISR。此外,根据其潜在反应性,PDA提供了在PDA功能化支架上固定一些相关药物以提供潜在协同效应的可能性。

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