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基因编码的生物相容性抗凝血蛋白涂层冠状动脉支架促进内皮化。

Genetically encoded biocompatible anti-coagulant protein-coated coronary artery stents drive endothelialization.

机构信息

Department of Biochemistry and Biotechnology, Council of Scientific and Industrial Research - Central Leather Research Institute, Chennai 600020, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, India; Sona College of Arts and Science, Salem 636005, India.

Department of Biochemistry and Biotechnology, Council of Scientific and Industrial Research - Central Leather Research Institute, Chennai 600020, India; Academy of Scientific and Innovative Research, Ghaziabad 201002, India.

出版信息

Colloids Surf B Biointerfaces. 2024 Jun;238:113908. doi: 10.1016/j.colsurfb.2024.113908. Epub 2024 Apr 8.

Abstract

In response to the critical demand for advancements in coronary artery stents, this study addresses the challenges associated with arterial recoil and restenosis post-angioplasty and the imperative to encourage rapid re-endothelialization for minimizing thrombosis risks. We employed an innovative approach inspired by mussel adhesion, incorporating placental anticoagulant protein (AnnexinV) on stent design. The introduction of a post-translationally modified catecholic amino acid L-3,4-dihydroxyphenylalanine (L-Dopa), mimicking mussel characteristics, allowed for effective surface modification of Stainless steel stents through genetic code engineering in AnnexinV (AnxDopa). The efficacy of AnxDopa was analyzed through microscale thermophoresis and flow cytometry, confirming AnxDopa's exceptional binding with phosphatidylserine and activated platelets. AnxDopa coated stainless steel demonstrates remarkable bio-, hemo-, and immuno-compatibility, preventing smooth muscle cell proliferation, platelet adhesion, and fibrin formation. It acts as an interface between the stent and biological fluid, which facilitates the anticoagulation and rapid endothelialization. Surface modification of SS verified through XPS analysis and contact angle measurement attests to the efficacy of AnxDopa mediated surface modification. The hydrophilic nature of the AnxDopa-coated surface enhanced the endothelialization through increased protein absorption. This approach represents a significant stride in developing coronary stents with improved biocompatibility and reduced restenosis risks, offering valuable contributions to scientific and clinical realms alike.

摘要

针对冠状动脉支架的关键需求,本研究解决了血管成形术后动脉回缩和再狭窄的挑战,以及鼓励快速内皮化以最小化血栓形成风险的必要性。我们采用了一种受贻贝粘附启发的创新方法,在支架设计中加入胎盘抗凝蛋白( AnnexinV )。通过对 AnnexinV ( AnxDopa )进行遗传密码工程,引入一种翻译后修饰的儿茶酚氨基酸 L-3,4-二羟基苯丙氨酸( L-Dopa ),模拟贻贝的特性,从而实现了不锈钢支架的有效表面修饰。通过微尺度热泳和流式细胞术分析了 AnxDopa 的功效,证实了 AnxDopa 与磷脂酰丝氨酸和活化血小板的特殊结合。AnxDopa 涂层的不锈钢表现出出色的生物、血液和免疫相容性,可防止平滑肌细胞增殖、血小板黏附和纤维蛋白形成。它作为支架和生物流体之间的界面,促进了抗凝和快速内皮化。XPS 分析和接触角测量证实了 SS 的表面修饰效果,证明了 AnxDopa 介导的表面修饰的有效性。AnxDopa 涂层表面的亲水性增强了蛋白质的吸收,从而促进了内皮化。这种方法在开发具有改善的生物相容性和降低再狭窄风险的冠状动脉支架方面取得了重大进展,为科学和临床领域都做出了有价值的贡献。

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