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Abstract
The use of medical devices is often complicated by surface-associated infection and thrombosis. This dissertation explores the versatility of S-nitrosothiols (RSNOs) in various formulations to address these issues. RSNOs are commonly used to provide prolonged nitric oxide (NO)-releasing platforms. As NO is an endogenous antimicrobial and antithrombotic agent, NO- releasing materials provide multifunctional interfaces for potential biomedical applications.
This work describes RSNOs in solution, covalently attached to a material for surface coating, and impregnated into medical-grade tubing. Each of these forms provide unique properties for a variety of potential applications. The first investigation employs S-nitrosoglutathione (GSNO) in saline as an antibacterial and antithrombotic lock solution for venous catheters. It was established to release NO for the full duration of a potential lock therapy (48 h). The NO-releasing lock solution routinely outperformed clinically used lock solutions in antibacterial and antithrombotic assays. It was also established to be biocompatible.
The second study attached the RSNO S-Nitroso-N-acetylpenicillamine (SNAP) to graphene oxide (GO) for biomaterial coatings. This novel material was thoroughly characterized via quantitative and qualitative analyses. It was demonstrated to have highly tunable NO release
profiles via changes in preparation and the use of low levels of electrical current. The NO-releasing GO showed superior antibacterial activity compared to unmodified GO in viable adhesion and biofilm dispersal assays. Moreover, it showed improved cytocompatibility.
The third investigation characterized SNAP-impregnated silicon rubber with a hydrophilic, polyethylene glycol (PEG) coating. The NO+PEG substrates showed complementary activities in preventing viable bacteria, plasma proteins, and platelets from adhering in vitro. Non- anticoagulated in vivo rabbit studies showed excellent resistance to clotting and significantly maintained patency compared to controls.
These various forms and applications of RSNOs demonstrate their versatility and their broad potential to be incorporated into many biomedical applications to help prevent infection and thrombosis.