Multiphasic studies on mechamistic asrects of Biocompatiblity of Materials used far Cardiouascular Devices

这项研究旨在评估用于心血管人工设备的血液接触表面的双相容性。由于参与血栓形成的机体防御机制的复杂性，我们进行了一项多阶段的研究，以确定血液/材料界面生物反应的性质和大小。新开发的测定接触活化度的定量方法清楚地区分了促凝血表面和内表面。使用纯化的凝血因子和补体因子的重组系统的研究表明，在分子水平上清楚地理解了两个生物系统在激活初始状态的分子事件。另一方面，人工合成的四肽(Arg-Gly-Asp-Ser)可剂量依赖地抑制吸附蛋白介导的血小板黏附，四肽是纤维蛋白原、纤维连接蛋白和玻璃连蛋白等黏附蛋白的共同黏附部位。这些研究从每个生物体系的表面反应性-生物活化输入一个一般的“表面性质-生物关系”，它将作为生物相容表面的分子设计的逻辑基础。

This study aims to assess the bicompatibility of blood-contacting surfaces used for cardiovascular artificial devices. Due to the complex nature of body defense mechanisms involving in the thrombus formation, a multiphasic study was conduced to determine the nature and magnitude of the biological responses at blood/material interfaces. Newly-developed quantitative assay method determining the degree of contact activation clearly differentiated the coagulation-promoting surfaces and innert surfaces. The studies using reconstituted systems using purified coagulation and complement factors showed that the molecular events at the initial states of activation of both biological systems were clearly understood at molecular level. On the other hand, the platelet adhesion mediated via adsorbed polasma proteins were inhibited in a dose-dependent manner by using synthetic tetrapeptida (Arg-Gly-Asp-Ser) which was recently identified as the common attachment site of adhesive proteins such as fibrinogen, fibronectin and vitronectin. These studies compiled from the surface reactivity-biological activation of each biological systems input a general "Surface Property-Biological Relationshuip", which will serve as a logical basis of the molecular design of biocompatible surfaces.l serve as a logical basis of the molecular design