Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules |
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| Authors: | Cong Li Hui Du Aizhen Yang Shuaibing Jiang Zhenhua Li Dan Li John L Brash Hong Chen |
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| Affiliation: | 1. State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry,, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu, P. R. China;2. Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, P. R. China;3. School of Biomedical Engineering and Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada |
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| Abstract: | 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. |
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| Keywords: | antithrombotic materials coating fibrinolysis nanocapsules thrombin‐responsive materials |
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