A NOVEL APPROACH TO NONTHROMBOGENIC POLYMER SURFACES

过去几年，我们在以下方面取得了重大进展： 新诺明预防体表血栓形成的机理研究 表面改性方法。在珍贵的应用中，肝素 使用动态亲水间隔基团固定聚合物表面(通过In SPU-PEO-肝素接枝的原位表面固定和包覆 共聚物)显示显著减少血栓的形成 在体外、体外和体内的表面研究。 在这一更新应用中，我们建议对医用聚合物表面进行改性 使用表面固定化基因工程抗栓剂 (水飞蓟素)和纤溶(t-PA)试剂。将使用水飞蓟素和t-PA 因为它们显示出明显的药理优势 常用的肝素和尿激酶分别。 将引入新的表面放大化学来固定化 水飞蓟素或t-PA在聚合物表面，基于我们的亲水间隔物 假设。预计放大聚合物和PEO的使用 间隔物可以增加表面的生物活性以及表面 固定化试剂的浓度。此外，动态的 血液/聚合物界面的亲水环境可以减少蛋白质 吸收和血小板相互作用。固定化水蛭素(或t-PA) 表面应通过以下方式抑制表面诱导血栓的形成 水蛭素的凝血酶抑制作用(即血小板活化和纤维蛋白 形成)或通过t-PA的纤溶活性。详细的镇压 机制将在体外和体内研究中进行探讨。已获得 结果将与我们之前研究的结果相关联 肝素固定化表面。这些有价值的信息将被用来 使用遗传技术为表面行为提供更有效的模型 工程生物活性物质和设计与血液接触的医疗设备。

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.