IMMOBILIZED FATTY ACIDS FOR REVERSIBLE ALBUMIN BINDING

用于可逆白蛋白结合的固定化脂肪酸

• 批准号: 2445244
• 负责人: PETER H DUQUETTE
• 金额: $ 42.64万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2445244
• 关键词: albumins; antithrombogenic surface; binding proteins; biomaterial compatibility; biomaterial development /preparation; chemical synthesis; dogs; fatty acid analog; fibrinogen; human tissue; implant; mass spectrometry; mitral valve; photoactivation; plastics; polymers; sheep

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.

必须改进血液接触医疗器械中使用的材料， 减少表面诱导的血栓形成。 第二阶段的目标 该项目是将脂肪酸类似物添加到生物材料上， 结合内源性白蛋白，从而改善他们的血液 兼容性. 在阶段I期间，八种脂肪酸的光活化类似物 合成酸，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 血栓形成性。 一种试剂似乎特别有希望用于 增强白蛋白结合并减少血小板附着， activation. 在第二阶段，光活化聚丙烯酰胺与侧脂肪 酸和含有脂肪酸的异双官能PEG衍生物将 合成并固定在聚乙烯，硅橡胶， 聚氯乙烯和聚氨酯。ESCA和TOF-SIMS将用于 确保固定化脂肪的存在、完整性和均匀性 acids.表面改性材料将受到磨损的挑战， 消毒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 将在体外测试粘附和活化。 急性，犬颈静脉 将进行植入以筛选表面以改善血液 兼容性.在筛选试验中表现良好的表面将 在14天和90天的绵羊颈动脉植入物和5个月的 绵羊二尖瓣植入物。 建议的商业应用：材料的开发， 在医疗装置市场中需要增强的血液相容性。 的 将脂肪酸引入到 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 对改进这些设备有重大影响，因此， 具有巨大的商业潜力。