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Abstract
Blood-contacting medical devices are routinely impacted by two clinical complications: infection and device-induced thrombosis. Due to nitric oxide (NO)’s endogenous role as an antimicrobial and antithrombotic agent, NO-releasing platforms have gained tremendous popularity for combatting both clotting and infection. However, NO-releasing materials have three major shortcomings that limit commercial applications: (1) a limited NO reservoir, (2) a lack of NO release tunability, and (3) an inability to prevent biofouling. In this dissertation work, NO-releasing materials were combined with different surface strategies to improve the longevity, tunability, and antifouling properties of NO-releasing platforms. In the first approach, a novel polymeric platform that could explicitly release NO from the material’s NO reservoir as well as generate NO from interaction with endogenous NO donors was demonstrated using an S-nitroso-N-acetylpenicillamine (SNAP)-doped polymer with a selenium interface. The SNAP-Se platform exhibited potent antimicrobial activity (>99% reduction in Staphylococcus aureus and Escherichia coli) and reduced in vitro platelet adhesion by 85.5% compared to controls.
In the second approach, polymeric coatings containing the NO donor S-nitrosoglutathione (GSNO) and a copper nanoparticle catalyst were applied to commercial poly(vinyl chloride) tubing for the tunable, elevated release of NO. The addition of copper increased the NO flux up to five times higher, resulting in superior in vitro antimicrobial activity (96-99.9% reduction in S. aureus and Pseudomonas aeruginosa) and in vivo hemocompatibility in a 4 h extracorporeal rabbit model, maintaining 89.3% of baseline platelet counts while controls only maintained 67.6%.
In the third approach, SNAP-based silicone rubber platforms were infused with silicone oil (Si) to combine the multifunctional properties of NO with an antifouling, liquid-infused interface. The combined platform demonstrated potent antibacterial activity against methicillin-resistant S. aureus and P. aeruginosa for up to 28 days. Moreover, SNAP-Si cannulas evaluated in a 14- and 21-d subcutaneous mouse model enhanced material biocompatibility by reducing the thickness of the fibrous encapsulation by ~60.9% and cell density around the implant by ~60.8% after 3 weeks.
The combined surface strategies significantly improved the properties of existing NO-releasing platforms, demonstrating excellent potential in reducing rates of infection and thrombosis commonly associated with medical device applications.