NOVEL APPROACH TO NONTHROMBOGENIC POLYMER SURFACES

过去几年，我们在以下方面取得了重大进展： 新型抗血栓药物预防体表血栓形成的机制研究 表面改性方法 在珍贵的应用中，肝素 使用动态亲水性间隔基团的固定化聚合物表面（通过在 SPUU-PEO-肝素接枝物原位表面固定化及包覆 共聚物）显示出显著减少血栓形成， 在体外、离体和体内研究中， 在这个更新的应用程序中，我们建议修改医用聚合物表面 使用表面固定的基因工程抗血栓形成剂 （水蛭素）和纤维蛋白溶解（t-PA）剂。 水蛭素和t-PA将被用于 因为它们表现出明显的药理学优势， 常用的肝素和尿激酶。 新的表面放大化学将被引入到生物传感器中。 水蛭素或t-PA在聚合物表面，基于我们的亲水性间隔 假说. 预期放大聚合物和PEO的使用 间隔物可以增加表面生物活性以及表面 固定化试剂的浓度。 此外，动态 血液/聚合物界面处的亲水性环境可以减少蛋白质 吸收和血小板相互作用。 水蛭素（或t-PA）固定化 表面应抑制表面诱导血栓的形成， 水蛭素凝血酶凝集（即，血小板活化和纤维蛋白 形成）或通过t-PA的纤溶活性。 详细的抑制 将在体外和体内研究中研究其机制。 获得 结果将与我们以前的研究结果相关联， 肝素固定表面。 这些宝贵的信息将用于 提供了一个更有效的模型，表面行为，使用遗传 工程生物活性剂和设计血液接触医疗器械。

Over the past several years, we have made significant progress in the mechanistic study of surface thrombus formation and prevention using novel surface modification methods. In the precious application, heparin immobilized polymer surfaces using dynamic hydrophilic spacer groups (by in situ surface immobilization and coating of SPUU-PEO-Heparin graft copolymer) demonstrated a significant reduction in thrombus formation on surfaces in in vitro, ex vivo and in vivo studies. In this renewal application, we propose to modify medical polymer surfaces using surface immobilized genetically engineered antithrombotic agent (Hirudin) and fibrinolytic (t-PA) agents. Hirudin and t-PA will be used because they demonstrate distinct pharmacologic advantages over the more commonly used heparin and urokinase, respectively. Novel surface amplification chemistry will be introduced to immobilize Hirudin or t-PA on the polymer surfaces, based on our hydrophilic spacer hypothesis. It is expected that the use of amplifying polymer and PEO spacer can increase surface bioactivity as well as the surface concentration of the immobilized agents. In addition, the dynamic hydrophilic environment at the blood/polymer interface can reduce protein absorption and platelet interaction. Hirudin (or t-PA) immobilized surfaces should suppress the formation of surface-induced thrombi by Hirudin's thrombin inhibitation (i.e., platelet activation and fibrin formation) or by t-PA's fibrinolytic activity. The detailed suppression mechanism will be investigated in both in vitro and vivo studies. Obtained results will be correlated with results form our previous studies of heparin immobilized surfaces. This valuable information will be used to provide a more effective model for surface behavior using genetically engineered bioactive agents and to design blood contacting medical devices.