CELL AND PROTEIN REACTIONS WITH FOREIGN MATERIALS

说明了对增强血液相容性的生物材料的需求 人工合成小直径血管移植物的失败和栓塞 与人工心脏相关的并发症。改进了 接触血液或软组织的生物材料有待更好的了解 所涉及的分子和细胞过程。因为蜂窝电话 与生物材料的相互作用强烈地受数量和 接触时形成的吸附层中特定蛋白质的反应性 对于生物体液，一系列关于 吸附蛋白质层的组织和细胞相互作用是 建议。 在这项工作中将使用几类聚合物，包括：(1) 聚氨基甲酸酯；(2)射频等离子体沉积薄膜；(3)聚环氧乙烷 表面；和(4)甲基丙烯酸聚合物。血小板黏附、扩散和 释放将与纤维蛋白原(FGN)、纤维连接蛋白(FN)、免疫球蛋白G和 VWF从血浆中吸附。血小板/吸附蛋白的相互作用将是 用阻断FN和FGN与血小板结合的多肽进行研究， 特异性吸附蛋白的抗体封闭和细胞印迹 能够揭示血小板中其他蛋白质重要性的技术 互动。血小板对蛋白质如何被吸附的反应，而不是 只有其中有多少被吸附，将使用一系列 共吸附蛋白(包括白蛋白/FGN和白蛋白/FN)。的影响 老化对预吸附蛋白质与细胞相互作用的影响 检查是因为这似乎改变了蛋白质的构象 表面密封性的增加证明了这一点 蛋白质是固定的。巨噬细胞黏附、扩散和生长因子 将释放与免疫球蛋白和C3在几种聚合物上的吸附进行比较 系列片。细胞印迹、抗体封闭、共吸附和蛋白质老化 也将在这个系统中进行研究。内皮细胞(两者 牛主动脉和人大隐动脉)将在射频等离子体上培养 特定增强血清对FN的吸附的改性表面 寻找可以改善血管内皮化的治疗方法 嫁接。FN和生长因子的吸附将在这些上进行测量 表面。使用预吸附的生长因子和/或肝素促进 极快的内皮细胞生长和细胞层的牢固粘连 对衬底的影响进行了研究。

The need for biomaterials with enhanced blood compatibility is illustrated by the failure of synthetic small diameter vascular grafts and the embolic complications associated with the artificial heart. Improvement of biomaterials which contact blood or soft tissue awaits better understanding of the molecular and cellular processes involved. Since the cellular interactions with biomaterials are strongly influenced by the amount and reactivity of specific proteins in the adsorbed layer formed on contact with biological fluids, a series of studies on the relationship between the organization of the adsorbed protein layer and cellular interactions is proposed. Several classes of polymers will be used in this work, including: (1) polyurethanes; (2) RF-plasma deposited films; (3) poly(ethylene oxide) surfaces; and (4) methacrylic polymers. Platelet adhesion, spreading, and release will be compared with fibrinogen (FGN), fibronectin (FN), IgG, and VWF adsorption from plasma. Platelet/adsorbed protein interactions will be studied with peptides which block FN and FGN binding to platelets, with antibody blocking of specific adsorbate proteins, and with a cell blotting technique capable of revealing the importance of other proteins in platelet interactions. Platelet response to how a protein is adsorbed, rather than only how much of it is adsorbed, will be examined using a series of co-adsorbed proteins (including albumin/FGN and albumin/FN). The effect of aging on pre-adsorbed proteins on their interactions with cells will be examined because this appears to alter the conformation of the protein on the surface as evidenced by increases in the tightness with which the proteins are held. Macrophage adhesion, spreading and growth factor release will be compared to IgG and C3 adsorption on several polymer series. Cell blotting, antibody blocking, co-adsorbate, and protein aging studies will be done in this system as well. Endothelial cells (both bovine aortic and human saphenous) will be grown in culture on RF-plasma modified surfaces that specifically enhance FN adsorption from serum to find a treatment which could improve the endothelialization of vascular grafts. FN and growth factor adsorption will be measured on these surfaces. The use of preadsorbed growth factor and/or heparin to promote extremely rapid endothelial cell growth and firm adhesion of the cell layer to the substrate will be studied.