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Abstract
The long-term success of blood-contacting medical devices remains challenged by surface-induced complications such as thrombosis and infection. Nitric oxide (NO)-releasing materials have demonstrated promising antibacterial and platelet-modulating properties; however, most fail to advance to clinical application due to unresolved challenges. Key limitations of current hemocompatible materials include the lack of effective strategies against multidrug-resistant bacterial colonization, limited understanding of NO-releasing surface interactions with blood proteins, and insufficient data on their long-term hemocompatibility in vivo. This dissertation addresses these challenges by developing hemocompatible composites that integrate bioactive and bioinert surface modification strategies. Specifically, NO-releasing materials were designed to enhance antibacterial efficacy and thromboresistance while mitigating foreign body responses. Key developments include the incorporation of S-nitroso-N-acetylpenicillamine-functionalized ampicillin into medical-grade polymers to combat antibiotic-resistant bacteria, the fabrication of a NO-releasing surface with enhanced albumin affinity to reduce fouling, and the modification of surface topography using soft lithography to improve hemocompatibility. Additionally, an endothelium-mimicking surface was developed by integrating bioactive and bioinert design strategies to optimize long-term device performance. The performance of the material was validated in a 28-day infectious thrombosis model in vivo.
This work provides a foundation for advancing the development of a truly hemocompatible surface and offers potential pathways for the clinical translation of NO-releasing biomaterials in medical device applications.