基于凝血酶可降解组织纤溶酶原激活物（t-PA）纳米胶囊的血栓反应性溶栓涂层,Advanced Functional Materials

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基于凝血酶可降解组织纤溶酶原激活物（t-PA）纳米胶囊的血栓反应性溶栓涂层
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2017-10-10 , DOI: 10.1002/adfm.201703934
Cong Li ₁ , Hui Du ₁ , Aizhen Yang ₂ , Shuaibing Jiang ₁ , Zhenhua Li ₁ , Dan Li ₁ , John L. Brash _{1,

3} , Hong Chen ₁

Affiliation

用能够抵抗血栓形成的生物活性剂进行的表面修饰是开发抗血栓形成的生物材料的广泛使用的策略。但是，在正常情况下，血液暴露于材料表面的抗血栓形成剂可能会导致止血失调。理想情况下，植入的生物材料应根据需要对生理环境中的特定变化做出适当的响应，就像发生在身体本身中一样。在本研究中，据报道具有血栓形成反应性的表面涂层，具有溶解血纤蛋白的能力。涂层由纳米胶囊（NCs）组成，其中纤维蛋白溶解活化剂t-PA封装在可凝血酶降解的水凝胶壳中。t-PA NCs通过聚多巴胺粘合剂层共价连接到多种材料上。用防污剂谷胱甘肽（GSH）处理所得表面，以防止与血液/血浆成分的进一步相互作用。t-PA NCs / GSH涂层表面稳定且在正常血浆环境中保持惰性，同时释放t-PA并在存在凝血酶的情况下促进纤维蛋白溶解。纤溶活性随凝血酶浓度的增加而增加，并因此随血栓形成的程度而增加。这项工作构成了抗凝血涂层的首次报道，其功能分别由凝血酶的出现和凝血程度来触发和调节。t-PA NCs / GSH涂层表面稳定且在正常血浆环境中保持惰性，同时释放t-PA并在存在凝血酶的情况下促进纤维蛋白溶解。纤溶活性随凝血酶浓度的增加而增加，并因此随血栓形成的程度而增加。这项工作构成了抗凝血涂层的首次报道，其功能分别由凝血酶的出现和凝血程度来触发和调节。t-PA NCs / GSH涂层表面稳定且在正常血浆环境中保持惰性，同时释放t-PA并在存在凝血酶的情况下促进纤维蛋白溶解。纤溶活性随凝血酶浓度的增加而增加，并因此随血栓形成的程度而增加。这项工作构成了抗凝血涂层的首次报道，其功能分别由凝血酶的出现和凝血程度来触发和调节。

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Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules

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.

更新日期：2017-10-10

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