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通过聚多巴胺将直接凝血酶抑制剂比伐卢定固定在 316L 不锈钢上及其对体外血液相容性的影响。

Immobilization of the direct thrombin inhibitor-bivalirudin on 316L stainless steel via polydopamine and the resulting effects on hemocompatibility in vitro.

机构信息

Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, China.

出版信息

J Biomed Mater Res A. 2012 Sep;100(9):2421-30. doi: 10.1002/jbm.a.34143. Epub 2012 May 5.

Abstract

Bivalirudin (BV), a peptidic direct thrombin inhibitor, derived from hirudin, has gained increasing interest in clinical anticoagulant therapy in the recent years. In this work, a hemocompatible surface was prepared by immobilization of BV on 316L stainless steel (SS) using a bonding layer of polydopamine (DA). X-ray photoelectron spectroscopy (XPS) was used to determine the chemical composition of the surfaces to characterize polydopamine intermediate layer and the immobilized BV. The quantity of bound BV was measured by quartz crystal microbalance (QCM). The hemocompatibility in vitro was evaluated by coagulating time of activated partial thromboplastin time (aPTT) and prothrombin time (PT) assay, platelet adhesion and activation, fibrinogen adsorption, and activation and whole blood test. The effect of sterilizing method on the bioactivity of immobilized BV was also evaluated. The results showed that BVs were successfully immobilized on SS surface with the DA interlayer at a density of 98 ng/cm(2) . BV coating surface prolonged aPTT and PT, inhibited the activation of platelet and fibrinogen significantly. Sterilization by ultraviolet radiation was possible with only marginal loss of activity. Thus, the approach described here may provide a basis for the preparation of 316L SS surface modification for use in cardiovascular implants.

摘要

比伐卢定(BV)是一种从水蛭素衍生而来的肽类直接凝血酶抑制剂,近年来在临床抗凝治疗中受到越来越多的关注。本工作通过多巴胺(DA)中间层将 BV 固定在 316L 不锈钢(SS)表面,制备了一种具有血液相容性的表面。X 射线光电子能谱(XPS)用于确定表面的化学成分,以表征聚多巴胺中间层和固定化的 BV。通过石英晶体微天平(QCM)测量结合的 BV 量。通过激活部分凝血活酶时间(aPTT)和凝血酶原时间(PT)测定、血小板黏附和激活、纤维蛋白原吸附以及全血试验评估体外血液相容性。还评估了灭菌方法对固定化 BV 生物活性的影响。结果表明,BV 成功地固定在 SS 表面,带有 DA 中间层,密度为 98ng/cm(2)。BV 涂层表面延长 aPTT 和 PT,显著抑制血小板和纤维蛋白原的激活。仅轻微失活即可通过紫外线辐射进行灭菌。因此,这里描述的方法可能为心血管植入物用 316L SS 表面改性提供基础。

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