PLATELET ACTIVATION & POLYMER SURFACE THROMBOGENICITY

目的是了解血小板粘附和活化是如何受到影响的 通过聚合物的表面性质， 在生物医学应用中的潜力，并将这些反应与 它们对血栓形成的影响。 纯化的人血小板在聚合物表面上的活化， 先前已通过X射线光电子能谱、接触 角，和其他技术;将研究扫描电子 显微镜，高压电子显微镜，并在生活状态下，由 视频增强微分干涉对比光学显微镜。 形态改变、时间和细胞骨架重组的差异 血小板表面形态变化率、外观和运动性 受体和颗粒分泌将针对每个表面进行分析。 单克隆抗体和特异性配体与胶体金结合 将被用作探针，通过光和 电镜 然后将分析形状变化的差异 使用药理学试剂来改变激活、受体表达和 细胞骨架重组 这些观察结果将与 聚合物物理化学性质。 此外，三个参数 将在体外分析影响血栓形成的血小板功能， 不同的聚合物。 这些是：血小板致密颗粒分泌， 光致发光ATP测定，受体的免疫金珠研究 表达和血小板激动剂诱导的活化程度。 通过迭代过程，具有其他表面性质的聚合物将 接受检查。 最终，聚合物表面性质的测定 其在调节血小板粘附和活化中是重要的， 需要的话 了解血小板如何响应具有不同 表面性质可以为开发具有最小 在循环中产生不良影响。 知识 血小板改变其对表面反应的机制， 通过药理学手段，也可能导致改善抗凝血 治疗时，人造材料被放置在循环。 在 此外，还观察了受体的外观和运动，以及颗粒 分泌将有助于更好地了解血小板在 调节血栓形成和改进的体外表面活性剂测定 血栓形成性

The aim is to understand how platelet adhesion and activation are affected by surface properties of polymers which have been chosen for their potential in biomedical applications, and to relate these responses to their effects on thrombogenicity. The activation of purified human platelets on polymer surfaces, which have been previously characterized by X-ray photoelectron spectroscopy, contact angle, and other techniques; will be studied by Scanning Electron Microscopy, High Voltage Electron Microscopy, and in the living state, by Video-enhanced Differential Interference Contrast Light Microscopy. Differences in cytoskeletal reorganization during shape-change, time and rate of shape-change, appearance and motility of platelet surface receptors, and granule secretion will be analyzed for each surface. Monoclonal antibodies and specific ligands conjugated to colloidal gold will be employed as probes to follow receptor motility by both light and electron microscopy. Differences in shape-change will then be analyzed using pharmacologic agents to modify activation, receptor expression, and cytoskeletal reorganization. These observations will then be related to polymer physicochemical properties. Additionally, three parameters of platelet function which affect thrombogenesis will be analyzed in vitro for the different polymers. These are; platelet dense granule secretion by photoluminescence ATP assay, immuno-gold bead studies of receptor expression, and the extent of activation inducible by platelet agonists. With an iterative process polymers with other surface properties will then be examined. Ultimately, the determination of polymer surface properties which are important in modulating platelet adherence and activation is desired. An understanding of how platelets respond to polymers having different surface properties can provide a basis for developing polymers with minimal adverse effects when placed in the circulation. Knowledge of the mechanisms by which platelets alter their responses to surfaces, as studied through pharmacologic means, could also lead to improved anticoagulant therapies when artificial materials are placed in the circulation. In addition, the observations of receptor appearance and motility, and granule secretion will lead to a better understanding of the platelets' role in modulating thrombosis and to improved in vitro assays for surface thrombogenicity.