3 years ago

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
Aizhen Yang, Dan Li, Shuaibing Jiang, Cong Li, John L. Brash, Zhenhua Li, Hui Du, Hong Chen
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. A novel thrombolytic coating whose activity is triggered by thrombosis is developed. The coating consists of thrombin-degradable tissue-type plasminogen activator (t-PA) nanocapsules. The coated surfaces remain inert in normal plasma environment while releasing t-PA and promoting fibrinolysis when thrombin is present. Such coating could avoid unfavorable complications caused by inherent antithrombotic activity in the case of traditional antithrombotic materials.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201703934

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