IN-VIVO EVALUATION OF SURFACE-INDUCED THROMBOGENESIS

在许多情况下，例如血管假体，它是长的- 聚合物生物材料的术语性能将决定 它们在临床上的用途。改良型汽车的开发研究进展 生物材料和对人工关节的作用机制的理解。 人工表面诱导的血栓形成必须包括评估 影响长期生物相容性的因素。我们 建议使用开发的一种慢性犬体外分流技术 在我们的实验室里调查聚合物的影响 长期血液的材料表面和体积特性 兼容性。在慢性病模型中获得的数据将是 与以前使用类似材料获得的结果相关联 在我们的急性犬类体外实验中。作为……的附庸 血栓形成(血小板活化、血小板沉积等)AS 关于血液相容性的描述，我们将使用慢性模型 在通畅性/故障是终点决定因素的研究中 生物兼容性。不同的流速和接触时间 血液接触将用于测试材料的性能 可能在临床上更相关的情况。慢性 体外实验将提供有关解吸和 放射性标记血浆蛋白在聚合物表面的交换 超过急性模型规定的两小时限制的时间。 钝化蛋白(如白蛋白和转铁蛋白)的作用 在长期血液暴露方面将有所探索。的影响 血管内皮细胞种植对其长期生物相容性的影响 聚合物材料将根据抗凝血性进行评估。 以及慢性体外模型的通畅率/失败率。这些 研究将与聚合物的体外研究相关联 表面-蛋白质-内皮细胞相互作用。生物降解性 在长期的血液接触过程中可能出现的聚合物表面， 将通过植入后的体积和表面特征进行评估 凝胶渗透层析等技术，动态 机械测试。傅里叶变换红外光谱分析 衰减全反射(FTIRATR)，扫描电子 显微镜和x射线光电子能谱。体外研究 使用单组分和多组分的酶混合物和脂/酶 混合体将试图阐明参与其中的途径 医用级聚合物及其改性材料的生物降解性 聚氨基甲酸酯。这些研究将使我们更好地理解 人工表面诱导的机制 血栓形成并将有助于生物相容性的设计 聚合材料。

In many instances, for example vascular prosthesis, it is the long- term performance of polymeric biomaterials that will determine their clinical usefulness. Advances in the development of improved biomaterials and in the understanding of the mechanisms of arti- ficial surface-induced thrombogenesis must include the assessment of those factors which influence long-term biocompatibility. We propose to use a chronic canine ex vivo shunt technique developed in our laboratory to investigate the influence of polymeric material surface and bulk properties on long-term blood compatibility. Data obtained in the chronic model, will be correlated with that previously obtained for similar materials used in our acute canine ex vivo experiments. As an adjunct to thrombogenicity (platelet activation, platelet deposition etc.) as a description of blood compatibility, we will use the chronic model in studies where patency/failure is the endpoint determinant of biocompatibility. Various flow rates and durations of exposure to blood contact will be used to test material performance in conditions which are possibly more clinically relevant. Chronic ex vivo experiments will provide information on the desorption and exchange of radiolabeled plasma proteins on polymer surfaces over periods in excess of the two hour limit imposed by the acute model. The role of passivating proteins (e.g. albumin and transferrin) in long-term blood exposure will be explored. The effect of endothelial cell seeding on the long-term biocompatibility of polymeric materials will be evaluated in terms of thromboresistance and patency/failure rates in the chronic ex vivo model. These studies will be correlated with in vitro studies of polymer surface-protein-endothelial cell interactions. The biodegradation of polymer surfaces that may occur during long-term blood contact, will be evaluated by post implant bulk and surface characterization techniques such as Gel permeation chromatography, dynamic mechanical testing. Fourier Transform Infrared Spectroscopy with attenuated total Reflectance (FTIRATR), scanning electron microscopy, and x-ray photoelectron spectroscopy. In vitro studies using single and multi-component enzyme mixtures and lipid/enzyme mixtures will attempt to elucidate the pathways involved in the biodegradation of medical grade polymers and modified polyurethanes. These studies will lead to a better understanding of the mechanisms involved in artificial surface-induced thrombogenesis and will aid in the design of biocompatible polymeric materials.