IMMOBILIZED FATTY ACIDS FOR REVERSIBLE ALBUMIN BINDING

接触血液的医疗器械中使用的材料必须改进为 减少表面诱发的血栓形成。这一阶段的目标是 该项目是将脂肪酸类似物固定在生物材料上，以增强 结合内源性白蛋白，从而改善他们的血液 兼容性。在第一阶段，八个脂肪的光活性类似物 合成了酸，并将其固定在聚氨酯、聚氯乙烯、 和聚乙烯，并在体外测试白蛋白结合和指示剂 血栓形成的可能性。一种试剂似乎特别有希望用于 增强白蛋白结合，减少血小板黏附 激活。 在第二阶段，具有悬垂脂肪的光活性聚丙烯酰胺 酸和含有脂肪酸的异双功能聚乙二醇衍生物将 合成并固定在聚乙烯、硅橡胶、 聚氯乙烯和聚亚安酯。ESCA和TOF-SIMS将用于 确保固定化脂肪的存在、完整和均匀 酸。表面改性的材料将受到磨损的挑战， 灭菌和洗涤以确定物理耐久性。白蛋白和 纤维蛋白原吸附、抗纤维蛋白原抗体结合和血小板 黏附和激活将在体外进行测试。犬急性颈静脉 将进行植入物以筛选表面以改善血液 兼容性。在筛选分析中表现良好的表面将 在14天和90天的绵羊颈动脉植入和5个月后进行测试 绵羊二尖瓣植入物。 拟议的商业应用：开发具有以下特性的材料 医疗器械市场需要增强血液相容性。这个 引入脂肪酸的光固定化技术 在这项拨款申请中提出的生物材料表面将很容易 适用于目前用于血液接触的几乎所有聚合物 医疗器械。因此，这种表面改性策略将具有 在改进这些设备方面产生重大影响，因此将 具有巨大的商业潜力。

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.