Thrombosis-Responsive Thrombolytic Coating Based on Thrombin-Degradable Tissue Plasminogen Activator (t-PA) Nanocapsules
Thrombosis-Responsive Thrombolytic Coating Based on Thrombin-Degradable Tissue Plasminogen Activator (t-PA) Nanocapsules
复制标题
基于凝血酶可降解组织纤溶酶原激活剂 (t-PA) 纳米胶囊的血栓响应溶栓涂层
DOI：
10.1002/adfm.201703934
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发表时间：
2017-12-01
影响因子：
19
通讯作者：
Chen, Hong
中科院分区：
文献类型：
--
作者：
Li, Cong;Du, Hui;Chen, Hong
用抗血栓形成的生物活性剂进行表面修饰是开发抗血栓生物材料的一种广泛使用的策略。然而，在正常情况下，血液暴露于材料表面的抗血栓剂可能导致止血障碍。理想情况下，植入的生物材料应该对生理环境的特定变化做出适当的反应，就像身体本身发生的变化一样。在目前的研究中，一种具有溶解纤维蛋白形成能力的血栓反应表面涂层被报道。该涂层由纳米胶囊（NCs）组成，其中纤溶激活剂t-PA被封装在凝血酶可降解的水凝胶壳中。t-PA NCs通过聚多巴胺粘合层以共价方式附着在几种材料上。所得表面用防污剂谷胱甘肽（GSH）处理，以防止与血液/血浆成分进一步相互作用。t-PA NCs/ gsh包被表面在正常血浆环境中保持稳定和惰性，当凝血酶存在时释放t-PA并促进纤维蛋白溶解。纤溶活性随着凝血酶浓度的增加而增加，因此可能与血栓形成的程度有关。这项工作构成了抗血栓涂层的第一份报告，其功能分别由凝血酶的出现和凝血程度触发和调节。
Surface modification with bioactive agents capable of combating thrombosis is a widely used strategy for developing antithrombotic biomaterials. However, exposure of the blood to the antithrombotic agent on the material surface may cause hemostatic disorders under normal conditions. Ideally an implanted biomaterial should respond appropriately on demand to a specific change in the physiologic environment, as happens in the body itself. In the present study, a thrombosis-responsive surface coating with the ability to lyse fibrin as it forms is reported. The coating consists of nanocapsules (NCs) in which the fibrinolysis activator t-PA is encapsulated in a thrombin-degradable hydrogel shell. The t-PA NCs are attached to several materials covalently through a polydopamine adhesive layer. The resulting surfaces are treated with the antifouling agent glutathione (GSH) to prevent further interactions with blood/plasma components. The t-PA NCs/GSH-coated surface is stable and remain inert in normal plasma environment while releasing t-PA and promoting fibrinolysis when thrombin is present. The fibrinolytic activity increases with increasing thrombin concentration, and therefore presumably with the extent of thrombosis. This work constitutes the first report of an antithrombotic coating whose function is triggered and regulated, respectively, by the appearance of thrombin and the extent of coagulation.