CELL AND PROTEIN REACTIONS WITH FOREIGN MATERIALS

缺乏对潜在的生化机制的了解 血液与聚合物生物材料的反应仍然是一种 这是设计更好的与血液接触的材料的障碍。 然而，有一个巨大的现有的和不断扩大的需求 与血液更相容的材料。建议数 研究将使生物材料的更合理设计发生在 寻找更好的材料是目前经验性的研究方向。此外, 由于将开发新材料来测试所提出的机制， 材料的改进可能直接来自于这项工作。具体目标 主要内容如下：1.进一步开发和应用一种新的、 原位、高精度、高分辨率的血小板研究方法 将完成与材料的相互作用。通过测量钙 当血小板接触聚合物表面时，在其内部的动员 使用新获得的冷却CCD百万像素相机和外延荧光 显微镜，一种强大的新工具将可用来让我们评估 表面性质在血小板活化中的作用。混凝 因子分析将使用相同的成像设备进行，使用 荧光记号笔。2.纤维蛋白原被吸附的假设是 血小板与聚合物生物材料黏附的主要介体将是 测试过。通过测量血小板对表面的黏附和活化 与血浆选择性耗尽或遗传缺陷吸附在 黏附蛋白纤维蛋白原、纤维连接蛋白、玻璃体连接蛋白和血管性血友病 Willebrand因子，我们将评估这些蛋白质的重要性。 补虚效果的剂量-反应研究 因素也将被做出来。3.检验一种假设，即血小板 生物材料的粘附性和活化性取决于以下物质的量 以及纤维蛋白原与材料结合的状态， 将研究四个系列聚合物上的血小板和纤维蛋白原。这个 使用的聚合物系列有：a)等离子沉积氟碳表面 用TFE制成，包括一种通过在TFe中沉积TFe而制成的新型 存在不同数量的H2或CH4；b)含有PVA和PEO 与纤维蛋白原结合较弱的聚合物。烷基化聚氯乙烯和 应表现出不同程度更紧密的PEO/PPO共聚物 还将研究：c)HEMA-EMA共聚物；d) 商用和新型聚氨基甲酸酯。表面表征数据将 与蛋白质吸附特性和血小板的相关性 使用多元统计方法的交互作用。

The lack of knowledge of the biochemical mechanisms underlying the reactions of blood with polymeric biomaterials continues to be an obstacle to the design of better materials for use in contact with blood. Yet there is a large existing and continually expanding need for materials that would be more compatible with blood. The proposed research will allow more rational design of biomaterials to occur in place of the current empirical search for better materials. In addition, since new materials will be developed to test the proposed mechanisms, improved materials may result directly from the work. The specific aims are as follows: 1. The further development and application of a new, in situ, high accuracy, high resolution method for studying platelet interactions with materials will be done. By measuring calcium mobilization inside platelets as they contact the surface of the polymer using a newly acquired cooled CCD megapixel camera and epi-fluorescent microscope, a powerful new tool will be available allowing us to assess the role of surface properties in platelet activation. Coagulation factor assays will be done using the same imaging equipment using fluorescent markers. 2. The hypothesis that adsorbed fibrinogen is the major mediator of platelet adhesion to polymeric biomaterials will be tested. By measuring platelet adhesion and activation to surfaces pre- adsorbed with plasma selectivity depleted or genetically deficit in the adhesion proteins fibrinogen, fibronectin, vitronectin, and von Willebrand factor, we will assess the importance of these proteins. Dose-response studies of the effect of restoration of the deficient factors will also be done. 3. To test the hypothesis that the platelet adhesion and activation by biomaterials are determined by the amount as well as the state of fibrinogen binding to the material, the behavior of platelets and fibrinogen on four series of polymers will be studied. The polymer series to be used are: a) plasma deposited fluorocarbon surfaces made with TFE, including a new type made by deposition of TFE in the presence of varying amounts of H2 or CH4; b) PVA and PEO containing polymers that exhibit weak binding of fibrinogen. Alkylated PVAs and PEO/PPO copolymers that should exhibit variable degrees of tighter binding will also be studied: c) HEMA-EMA copolymers; and d) commercial and novel polyurethanes. Surface characterization data will be correlated with protein adsorption characteristics and platelet interactions using multivariate statistical methods.