Dual surface modification of polydimethylsiloxane (PDMS) with antithrombin-heparin complex (ATH) and tissue plasminogen activator (t-PA) for enhanced antithrombotic activity

Medical devices used in contact with blood trigger coagulation and activate platelets leading to thrombotic complications. To prevent these effects, systemic anticoagulants and antiplatelet agents are typically prescribed, but these agents tend to increase the risk of bleeding. Modification of the surface of the blood-contacting material is an alternative approach to the inhibition of coagulation and thrombosis. In this work, the dual surface modification of polydimethylsiloxane (PDMS) with an antithrombin-heparin complex (ATH) to inhibit coagulation, and tissue plasminogen activator (t-PA) to lyse incipient clot, was investigated. Three different modification processes were used to immobilize ATH and t-PA: sequentially, with one component followed by the other; and with both components present simultaneously. Polydopamine (PDA) was used as a "bioglue" to enhance adhesion of the modifiers. The surface hydrophilicity and roughness were found to increase with increasing extent of modification. The surface density of the modifiers and their stability in plasma were significantly influenced by the modification process. The sequential method with t-PA first followed by ATH led to increased heparin activity. Data from plasma clotting time experiments showed that the combination of ATH and t-PA provides a synergistic effect, wherein both the anticoagulant activity of ATH and the clot lysis activity of t-PA on the surface are enhanced. This dual modification approach using both an anticoagulant and a thrombolytic agent shows promise to improve the blood compatibility of PDMS. The strategy can be applied to materials other than PDMS since the PDA coating is generic, thus providing a method for improving the performance of many blood-contacting devices.