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Abstract
Implanted medical devices, such as catheters, vascular grafts, and stents face critical challenges even as they are used in several thousand patients each year. The implanted materials are subjected to fundamentally critical challenges caused by thrombosis and infections. While thrombosis can cause subsequent device-failure accompanied by embolism and even deaths; a device that is not able to provide anti-infection properties can easily be contaminated through the microflora present on the skin of the patient and cause devastating problems such as bloodstream infections. 1.7 million cases of hospital-acquired infections in the U.S. alone cause approximately 99,000 deaths annually. These complications contribute to an annual expenditure of $28.4 to $33.8 billion in direct medical costs. Thus, these numbers have warranted a plethora of research to combat medical device associated thrombosis and infection. While an assortment of prevention methods has been researched and designed to create antithrombotic and antimicrobial materials, the search for the elusive ideal material that can provide a robust biocompatible environment remains active. Among the front runners in this quest for biocompatibility is the small endogenous gaseous molecule, nitric oxide (NO). It is a unique molecule that can offer both antimicrobial and antithrombotic properties to the material that it is incorporated in. Nitric oxide's multi mechanism-based antimicrobial strategies can be bactericidal towards the commonly found nosocomial pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli etc., and the antithrombotic properties have been known to be effective in both in vitro and in vivo environments for catheters and extracorporeal circulation. However, NO releasing materials cannot repel proteins, which are the most important biomacromolecules involved in biocompatibility for long term applications. Without antifouling properties, the surfaces can be easily fouled over time with proteins and start the coagulation cascade or allow resistant bacteria to settle down on the material's surface. This dissertation serves as a study to improve upon various NO-releasing materials' biocompatibility properties by coupling it with different antifouling strategies, thus paving the way towards a biocompatible environment for improved functioning of the medical device.