Active Release of an Antimicrobial and Antiplatelet Agent from a Nonfouling Surface Modification

Two major challenges faced by medical devices are thrombus formation and infection. In this work, surface-tethered nitric oxide (NO)-releasing molecules are presented as a solution to combat infection and thrombosis. These materials possess a robust NO release capacity lasting ca. 1 month while simultaneously improving the nonfouling nature of the material by preventing platelet, protein, and bacteria adhesion. NO's potent bactericidal function has been implemented by a facile surface covalent attachment method to fabricate a triple-action coating-surface-immobilized S-nitroso- N-acetylpenicillamine (SIM-S). Comparison of NO loading amongst the various branching configurations is shown through the NO release kinetics over time and the cumulative NO release. Biological characterization is performed using in vitro fibrinogen and Staphylococcus aureus assays. The material with the highest NO release, SIM-S2, is also able to reduce protein adhesion by 65.8 ± 8.9% when compared to unmodified silicone. SIM-S2 demonstrates a 99.99% (i.e., ∼4 log) reduction for S. aureus over 24 h. The various functionalized surfaces significantly reduce platelet adhesion in vitro, for both NO-releasing and non-NO-releasing surfaces (up to 89.1 ± 0.9%), demonstrating the nonfouling nature of the surface-immobilized functionalities. The ability of the SIM-S surfaces to retain antifouling properties despite gradual depletion of the bactericidal source, NO, demonstrates its potential use in long-term medical implants.