BIOMATERIAL SUBSTRATES-S EPIDERMIDIS & PATHOGENICITY

生物材料基质-S表皮

• 批准号: 3289404
• 负责人: ANTHONY G. GRISTINA
• 金额: $ 20.62万
• 依托单位: MEDICAL SCIENCES RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3289404
• 关键词: Staphylococcus epidermidis; Staphylococcus infection; adhesin; biomaterial development /preparation; extracellular matrix proteins; human tissue; laboratory rabbit; macrophage activating factor; myristates; phagocytosis; polysaccharides; polyurethanes; tissue /cell culture; virulence

This is a competitive renewal application requesting funds to continue our studies of Staphylococcus epidermidis, biomaterials and pathogenicity. Adherent strains of S. epidermidis are the most frequent cause of biomaterial-induced infections. It appears that the capacity of coagulase- negative staphylococci to adhere to the surfaces of biomaterials represents an important virulence attribute of these normal flora organisms. The significant features of biomaterial-centered infections are: (1) adherent colonization of surfaces, (2) production of extracapsular polysaccharides, and (3) persistence of infection due to impaired host defense mechanisms. Adhesion to surfaces is believed to depend in part on interactions involving extracapsular polysaccharides, matrix proteins, and the specific atomic geometry and electronic state of the biomaterial surface. Our preliminary studies indicate that attachment of S. epidermidis to biomaterial surfaces most likely involves surface polysaccharides and adhesive host proteins like fibronectin. In the case of titanium alloy, elemental surface segregations of vanadium also appear to favor adherence. In addition, we have observed that macrophages exhibit an impaired phorbol myristate acetate (PMA) -elicited oxidative burst after interaction with polymethylmethacrylate (PMMA). Macrophages exposed to PMMA also failed to respond to macrophage activation factor, which suggests that they are defective in terms of becoming primed. These deficits could explain the impaired killing of S. epidermidis at the biomaterial-tissue interface. In Aim 1, our preliminary data will be further explored by continuing our isolation, extraction, and purification studies of extracapsular polysaccharides of S. epidermidis RP-12 strain; in Aim 2, we will identify the dominant fraction(s) involved in primary binding and select the smallest oligosaccharide component which will competitively inhibit the binding of S. epidermidis to biomaterials or conditioning proteins. In Aim 3. the role of biomaterial (Ti6A14V) surface features (eg elemental segregations) will be evaluated as binding sites for S. epidermidis and for S. epidermidis exopolysaccharide fractions using energy dispersive x-ray analysis correlated with electron microscopy. In Aim 4, the role of biomaterials (Ti6A14V), polymethylmethacrylate, and polyurethane in phagocyte impairment will be investigated by determinations of oxidative metabolism and killing capacity of macrophages for S. epidermidis in the presence of selected biomaterials.

这是一个竞争性续订申请，申请资金以继续我们的 表皮葡萄球菌、生物材料及致病性研究。 表皮葡萄球菌的粘附性菌株是引起 生物材料引起的感染。似乎凝固酶的能力- 阴性葡萄球菌附着在生物材料表面代表 这些正常植物群生物的一个重要的毒力属性。这个 以生物材料为中心的感染的显著特征是：(1)粘附性 表面定植，(2)囊外多糖的产生， 以及(3)由于宿主防御机制受损而持续感染。 对表面的粘附力被认为部分取决于相互作用。 涉及囊外多糖、基质蛋白和特定的 生物材料表面的原子几何和电子态。我们的 初步研究表明，表皮葡萄球菌对 生物材料表面很可能含有表面多糖和 粘附性宿主蛋白，如纤维连接蛋白。就钛合金而言， 钒的元素表面偏析似乎也有利于粘附性。 此外，我们还观察到巨噬细胞的佛波醇受损。 肉豆蔻酸乙酸酯(PMA)与 聚甲基丙烯酸甲酯(PMMA)。暴露于PMMA的巨噬细胞也未能 对巨噬细胞激活因子的反应，这表明它们是 在成为底漆方面有缺陷。这些缺陷可以解释 在生物材料-组织界面上对表皮葡萄球菌的杀灭作用减弱。在……里面 目标1，我们的初步数据将通过继续我们的 囊外成分的分离、提取及纯化研究 表皮葡萄球菌RP-12菌株的多糖；在目标2中，我们将鉴定 参与初级结合的主要组分(S)，并选择 最小的寡糖成分，它将竞争性地抑制 表皮葡萄球菌与生物材料或条件蛋白的结合。在AIM 3.生物材料(Ti6A14V)表面特征(如元素)的作用 分离)将被评估为表皮葡萄球菌和 能量色散X射线衍射法测定表皮葡萄糖胞外多糖组分 分析结果与电子显微镜检查结果相一致。在目标4中， 生物材料(Ti6A14V)、聚甲基丙烯酸甲酯和聚氨酯 吞噬细胞损害将通过氧化测定进行调查 巨噬细胞对表皮葡萄球菌的代谢和杀伤能力 存在选定的生物材料。