BACTERIAL COLONIZATION OF SURGICAL BIOMATERIALS

生物材料和人工器官的开发与应用进展 由于严重的感染并发症而延误，并被夸大了 宿主炎症反应。生物材料植入物周围有一个 免疫功能不全、纤维炎症、整合缺陷区 由于表皮葡萄球菌和沙门氏菌的附着而容易感染 其他细菌，并由于宿主的细胞和体液免疫 微扰。这项建议针对的是调查和 缓和这些关键问题。我们的目标是进一步 细菌黏附机制与细胞免疫的研究 生物材料组织界面败血症的功能障碍成分 病因和治疗机制的综合研究方法 在动物模型中定义的。我们在AIM 1中的目标将测试 抗细菌抗体的体内外效果 粘附素在阻止生物材料定植中的作用 表皮葡萄球菌的菌株。这些研究将表明，如果 对高危人群进行免疫接种是一种有效的策略。目标2将 检验巨噬细胞将保留其氧化和 如果结合到生物材料上，表面会使杀伤力降至最低 修改。目标3将在体内测试一种新型药物的有效性 巨噬细胞表达增强杀伤力的机制 抵抗和清除以生物材料为中心的脓毒症。目标4将讲述 氧化锌表面微结构、成分和氧化物超微结构的作用 系统地改变单一合金系统Ti6A14V以因地制宜 细菌黏附和蛋白质吸附的模式。这最后一个目标 将包括对吸附模式的抗体免疫金研究 体内获得的条件膜的蛋白质及其相关发现 从高分辨率表面分析和细菌 粘附力。我们已经开发并测试了一种有效的动物模型， 将被用来检测抗黏附素抗体对 预防和清除生物材料感染(目标1)。巨噬细胞免疫 增强技术(AIM 3)和生物材料涂层和 条件性研究(目标2，4)也将利用动物模型。

Progress in the development and use of biomaterials and artificial organs has been delayed by the serious complications of infection and exaggerated host inflammatory responses. Biomaterial implants are surrounded by an immuno-incompetent, fibro-inflammatory, integration deficient zone which is susceptible to infection due to the adherence of S. epidermidis and other bacteria, and because of host cellular and humoral immune perturbation. This proposal is directed to the investigation and moderation of those crucial problems. Our objectives are to further characterize bacterial adherence mechanisms and the cellular immune dysfunction components of biomaterial tissue interface sepsis using an integrative investigative approach to causal and therapeutic mechanisms defined in an animal model. Our objective in AIM 1 will test the effectiveness in vitro and in vivo of antibodies against bacterial adhesins in blocking colonization of biomaterials by clinically relevant strains of Staphlococcus epidermidis. These studies will indicate if the immunization of at risk groups is an effective strategy. AIM 2 will examine the hypothesis that macrophages will preserve their oxidative and killing capacity if binding to biomaterials is minimized by surface modification. AIM 3 will test the effectiveness of a novel in vivo mechanism to prime macrophages to express augmented killing capacity in resisting and clearing biomaterial-centered sepsis. AIM 4 will relate the role of surface microstructure, composition and oxide ultrastructure of a systematically varied single alloy system Ti6A14V to site-specific patterns of bacterial adhesion and protein adsorption. This last objective will include antibody immunogold studies of the adsorption patterns of proteins of in vivo acquired conditioning films and relate these findings to data derived from high resolution surface analysis and bacterial adhesion. We have developed and tested an effective animal model which will be utilized to examine the ability of antiadhesin antibodies to prevent and clear biomaterial infection (AIM 1). The macrophage immune augmentation technique (AIM 3) and the biomaterial coating and conditioning studies (AIMS 2,4) will also utilize the animal model.