IMMOBILIZED SULFONATES FOR REDUCED THROMBOGENESIS

目前在接触血液的医疗器械中使用的材料必须 得到改善，以减少在 血液-生物材料界面。这个二期工程的目标是 是将磺酸盐固定在生物材料表面以增强 它们与血液的配合性。在一期工程中， 含有侧链磺酸盐的光活化聚丙烯酰胺 固定在聚氨酯、聚氯乙烯和聚乙烯上 并被证明具有改善血栓形成能力的潜力 这些常用的医疗器械材料。在第二阶段 项目中，含磺酸盐的聚丙烯酰胺将被 合成并固定在聚乙烯、硅橡胶上， 聚氯乙烯和聚亚安酯。染色、ESCA和TOF-SIMS 将用于确保存在、完整性和一致性 固定化的磺酸盐。表面改性的材料将是 挑战磨损、标准灭菌程序和 热循环，以确定其物理耐久性。吸附量 纤维蛋白原和其他血液蛋白，抗纤维蛋白原的结合 抗体，以及血小板黏附和激活将在 体外培养。将对急性犬颈静脉植入进行筛查 用于改善血液相容性的表面。表面 在筛查试验中表现最好的将在14- 以及90天的绵羊颈动脉植入。 建议的商业应用开发具有以下特点的材料 医疗器械市场需要增强血液相容性。 引入磺酸盐的光固定化技术 在这项拨款申请中提出的生物材料表面 几乎适用于目前使用的几乎所有聚合物 接触血液的医疗器械。因此，这个表面 修改策略将对改进产生重大影响 这些设备，因此，将具有重大的商业 潜力。

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.