IMMOBILIZED SULFONATES FOR REDUCED THROMBOGENESIS

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Materials used currently in blood-contacting medical devices must be improved to reduce thrombogenesis initiated at the blood-biomaterial interface. The objective of this Phase II project is to immobilize sulfonates onto biomaterial surfaces to enhance their compatibility with blood. In the Phase I project, photoactivatible polyacrylamides containing pendant sulfonates were immobilized on polyurethane, polyvinylchloride, and polyethylene and shown to have the potential to improve the thrombogenicity of these commonly used medical device materials. In the Phase II project, polyacrylamides with pendant sulfonates will be synthesized and immobilized onto polyethylene, silicone rubber, polyvinylchloride, and polyurethane. Staining, ESCA, and TOF-SIMS will be used to ensure the presence, completeness, and uniformity of the immobilized sulfonates. Surface-modified materials will be challenged with abrasion, standard sterilization procedures, and thermal cycling to determine their physical durability. Adsorption of fibrinogen and other blood proteins, binding of anti-fibrinogen antibodies, and platelet adhesion and activation will be tested in vitro. Acute, dog jugular vein implants will be conducted to screen the surfaces for improvements in blood compatibility. Surfaces which perform best in the screening assays will be tested in 14- and 90-day sheep carotid artery implants. PROPOSED COMMERCIAL APPLICATIONS The development of materials with enhanced hemocompatibility is needed in the medical device market. The photoImmobilization technology for introducing sulfonates 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.