BACTERIAL COLONIZATION OF SURGICAL BIOMATERIALS

外科生物材料的细菌定植

• 批准号: 2078597
• 负责人: ANTHONY G. GRISTINA
• 金额: $ 22.71万
• 依托单位: MEDICAL SCIENCES RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2078597
• 关键词: Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus infection; adsorption; alloys; biomaterial compatibility; biomaterial evaluation; biomaterial interface interaction; cellular immunity; disease /disorder model; fibronectins; immunochemistry; immunomodulators; laboratory rabbit; macrophage; microorganism culture; receptor; secondary infection; surface antigens

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.

生物材料和人工器官的开发与应用进展 由于感染的严重并发症而被推迟， 宿主炎症反应。生物材料植入物被一层 免疫缺陷、纤维炎性、整合缺陷区， 由于S.表皮葡萄球菌和 其他细菌，并由于宿主的细胞和体液免疫 扰动这项建议是针对调查和 解决这些关键问题。我们的目标是进一步 表征细菌粘附机制和细胞免疫 生物材料组织界面脓毒症的功能障碍成分 因果和治疗机制的综合研究方法 在动物模型中定义。我们在AIM 1中的目标将测试 抗细菌抗体体外和体内有效性 粘附素阻断生物材料定植的临床相关研究 表皮葡萄球菌菌株。这些研究将表明， 对高危人群进行免疫接种是一项有效的战略。AIM 2将 检查假设巨噬细胞将保持其氧化和 如果结合到生物材料上， 改性AIM 3将在体内测试一种新的 激发巨噬细胞表达增强的杀伤能力的机制 抵抗和清除以生物材料为中心的脓毒症。AIM 4将与 表面微观结构，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， 细菌粘附和蛋白质吸附的模式。最后一个目标 将包括抗体免疫金的吸附模式的研究， 体内获得的调节膜的蛋白质，并将这些发现 从高分辨率表面分析和细菌 粘连我们已经开发并测试了一种有效的动物模型， 将被用来检查抗粘附素抗体的能力， 预防和清除生物材料感染（AIM 1）。巨噬细胞免疫 增强技术（AIM 3）和生物材料涂层， 调节研究（AIMS 2，4）也将使用动物模型。