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定制的细胞外基质模拟涂层促进了心脏封堵器的再内皮化和组织愈合。

Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

机构信息

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

National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Biomaterials. 2025 Feb;313:122769. doi: 10.1016/j.biomaterials.2024.122769. Epub 2024 Aug 23.

Abstract

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

摘要

经导管微创介入治疗利用封堵器是治疗先天性心脏病和左心耳(LAA)血栓的主要方法。然而,封堵器植入后内皮化不完全和组织愈合延迟共同影响了临床疗效。在本研究中,我们定制了重组人源化胶原蛋白 I(rhCol I)并开发了基于 rhCol I 的细胞外基质(ECM)模拟涂层。该创新涂层将具有抗凝和抗炎功能的金属-酚醛网络作为弱交联剂与专门设计的 rhCol I 结合,rhCol I 具有高细胞黏附活性并引发低炎症反应。多种力的共同作用有效地使植入材料功能化,从而对封堵器植入后的微环境产生积极的响应。实验结果证实了该涂层能够持续发挥抗凝作用、增强内皮细胞和心肌细胞功能以及通过将炎症细胞极化成抗炎表型来调节炎症反应的能力。值得注意的是,在犬模型中进行的封堵器植入实验证实,该涂层可加速再内皮化过程并促进组织愈合。总的来说,这种定制的 ECM 模拟涂层为提高心脏封堵器的临床疗效提供了一种有前途的表面改性策略。

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