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多酚强化糖萼样水凝胶涂层诱导心肌再生和免疫调节。

Polyphenol-Reinforced Glycocalyx-Like Hydrogel Coating Induced Myocardial Regeneration and Immunomodulation.

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China.

Bioengineering Department, University of California, Los Angeles, California 90095, United States.

出版信息

ACS Nano. 2024 Aug 13;18(32):21512-21522. doi: 10.1021/acsnano.4c06332. Epub 2024 Aug 3.

Abstract

Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol-ene "click" reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG-TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the and signaling pathway.

摘要

尽管微创介入封堵器可以有效地封闭心脏缺陷组织,但它们仍然存在一些局限性,包括内皮愈合不良、强烈的炎症反应和血栓形成。在此,我们在心脏封堵器上制备了一种多酚强化的药物/肽糖萼样涂层。该涂层由羧化壳聚糖、表没食子儿茶素没食子酸酯(EGCG)、丹参酮 IIA 磺酸钠(TSS)和接枝有 3-氨基苯硼酸的透明质酸组成。随后,通过硫醇-烯“点击”反应接枝巯基丙酸-GGGG-Arg-Glu-Asp-Val 肽。该涂层表现出良好的亲水性和自由基清除能力,并且可以释放 EGCG-TSS。生物学实验结果表明,该涂层可以通过促进内皮化来减少血栓形成,并通过调节炎症反应来促进心肌修复。还证实了该涂层具有调节心肌细胞凋亡和代谢的功能,并且该涂层的炎症调节功能主要依赖于 NF-κB 和 MAPK 信号通路。

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