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在静态和动态条件下,用于改善冠状动脉支架应用的 TiO2 纳米结构的体外血液相容性和血管内皮细胞功能。

In vitro hemocompatibility and vascular endothelial cell functionality on titania nanostructures under static and dynamic conditions for improved coronary stenting applications.

机构信息

Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham University, Ponekkara PO, Cochin 682041, Kerala, India.

出版信息

Acta Biomater. 2013 Dec;9(12):9568-77. doi: 10.1016/j.actbio.2013.08.023. Epub 2013 Aug 22.

Abstract

The usefulness of nanoscale topography in improving vascular response in vitro was established previously on hydrothermally modified titanium surfaces. To propose this strategy of surface modification for translation onto clinically used metallic stents, it is imperative that the surface should be also hemocompatible: an essential attribute for any blood-contacting device. The present in vitro study focuses on a detailed hemocompatibility evaluation of titania nanostructures created through an alkaline hydrothermal route on metallic Ti stent prototypes. Direct interactions of TiO2 nanocues of various morphologies with whole blood were studied under static conditions as well as using an in vitro circulation model mimicking arterial flow, with respect to a polished Ti control. Nanomodified stent surfaces upon contact with human blood showed negligible hemolysis under constant shear and static conditions. Coagulation profile testing indicated that surface roughness of nanomodified stents induced no alterations in the normal clotting times, with insignificant thrombus formation and minimal inflammatory reaction. Endothelialized nanomodified Ti surfaces were found to inhibit both activation as well as aggregation of platelets compared with the control surface, with the endothelium formed on the nanosurfaces having an increased expression of anti-thrombogenic genes. Such a nanotextured Ti surface, which is anti-thrombogenic and promotes endothelialization, would be a cost-effective alternative to drug-eluting stents or polymer-coated stents for overcoming in-stent restenosis.

摘要

先前已证实,水热处理改良钛表面的纳米形貌可提高血管的体外反应。为了将这种表面改性策略应用于临床使用的金属支架,表面还必须具有良好的血液相容性:这是任何与血液接触的器械的基本属性。本体外研究专注于通过碱性水热途径在金属 Ti 支架原型上生成的 TiO2 纳米结构的详细血液相容性评估。研究了在静态条件以及模拟动脉血流的体外循环模型下,各种形态的 TiO2 纳米棒与全血的直接相互作用,同时以抛光 Ti 作为对照。纳米改性支架表面与人体血液接触时,在恒剪切和静态条件下几乎没有发生溶血。凝血特性测试表明,纳米改性支架的表面粗糙度不会改变正常的凝血时间,血栓形成轻微,炎症反应也最小。与对照表面相比,内皮化的纳米改性 Ti 表面可抑制血小板的激活和聚集,而纳米表面形成的内皮细胞具有增加的抗血栓形成基因表达。这种具有抗血栓和促进内皮化特性的纳米结构 Ti 表面,将是克服支架内再狭窄的药物洗脱支架或聚合物涂层支架的一种具有成本效益的替代方案。

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