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Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules
Author(s) -
Li Cong,
Du Hui,
Yang Aizhen,
Jiang Shuaibing,
Li Zhenhua,
Li Dan,
Brash John L.,
Chen Hong
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201703934
Subject(s) - materials science , nanocapsules , fibrinolysis , fibrin , thrombin , antithrombotic , plasminogen activator , coating , tissue plasminogen activator , biophysics , nanotechnology , chemistry , immunology , biochemistry , medicine , platelet , biology , nanoparticle
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.