IMMOBILIZED FATTY ACIDS FOR REVERSIBLE ALBUMIN BINDING

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Materials used in blood-contacting medical devices must be improved to reduce surface-induced thrombogenesis. The objective of this Phase II project is to immobilize fatty acid analogs onto biomaterials to enhance binding of endogenous albumin and, thereby, improve their blood compatibility. During Phase I, eight photoactivatible analogs of fatty acids were synthesized, immobilized on polyurethane, polyvinylchloride, and polyethylene, and tested in vitro for albumin binding and indicators of thrombogenicity. One reagent appeared particularly promising for enhancing albumin binding and reducing platelet attachment and activation. During Phase II, photoactivatible polyacrylamides with pendant fatty acids and heterobifunctional PEG derivatives containing fatty acids will be synthesized and immobilized onto polyethylene, silicone rubber, polyvinylchloride, and polyurethane. ESCA and TOF-SIMS will be used to ensure presence, completeness, and uniformity of the immobilized fatty acids. Surface-modified materials will be challenged with abrasion, sterilization, and washing to determine physical durability. Albumin and fibrinogen adsorption, anti-fibrinogen antibody binding, and platelet adhesion and activation will be tested in vitro. Acute, dog jugular vein implants will be conducted to screen surfaces for improvements m blood compatibility. Surfaces which perform well in the screening assays will be tested in 14- and 90-day sheep carotid artery implants and 5-month sheep mitral valve implants. PROPOSED COMMERCIAL APPLICATION: The development of materials with enhanced hemocompatibility is needed in the medical device market. The photoimmobilization technology for introducing fatty acids onto biomaterial surfaces proposed in this grant application would be readily applicable to nearly all polymers used currently in blood-contacting medical devices. Therefore, this surface modification strategy would have substantial impact in improving these devices and, consequently, would have significant commercial potential.