IMMOBILIZED SULFONATES FOR REDUCED THROMBOGENESIS

用于减少血栓形成的固定化磺酸盐

• 批准号: 2750377
• 负责人: PETER H DUQUETTE
• 金额: $ 37.17万
• 依托单位: SURMODICS, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-11-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750377
• 关键词: antithrombogenic surface; biomaterial compatibility; biomaterial development /preparation; chemical synthesis; mass spectrometry; photoactivation; polyacrylamide; polyethylenes; polyurethanes; polyvinyls; silicone rubber; stainings; sulfonate; thrombopoiesis

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.

目前用于血液接触医疗器械的材料必须 改善以减少血栓形成， 血液-生物材料界面第二阶段项目的目标 是将磺酸盐添加到生物材料表面， 与血液的相容性。在一期工程中， 含有磺酸酯侧基的光活化聚丙烯酰胺， 固定在聚氨酯、聚氯乙烯和聚乙烯上 并显示出具有改善血栓形成的潜力， 这些常用的医疗器械材料。II期 项目，聚丙烯酰胺与侧基磺酸盐将是 合成并固定在聚乙烯，硅橡胶， 聚氯乙烯和聚氨酯。 染色、ESCA和TOF-SIMS 将被用来确保存在，完整性和一致性 固定化的磺酸盐。表面改性材料将是 受到磨损、标准灭菌程序和 热循环以确定它们的物理耐久性。吸附 纤维蛋白原和其他血液蛋白的结合，抗纤维蛋白原 抗体、血小板粘附和活化将在 体外将进行急性犬颈静脉植入以筛选 改善血液相容性的表面。表面 在筛选试验中表现最好的将在14- 和90天的绵羊颈动脉植入。 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 引入磺酸盐的光固定化技术 在生物材料表面上， 可容易地应用于目前在聚合物领域中使用的几乎所有聚合物。 血液接触医疗器械。因此，该表面 修改策略将对改善 这些设备，因此，将具有显著的商业价值。 潜力