INFLAMATION AND INFECTION ON BIOMATERIALS

生物材料的炎症和感染

• 批准号: 2472603
• 负责人: STUART L COOPER
• 金额: $ 11.08万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-15 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2472603
• 关键词: bacteria infection mechanism; biomaterial compatibility; biomaterial interface interaction; biomaterials; blood proteins; cell adhesion; cellular immunity; cytotoxicity; digital imaging; extracellular matrix proteins; fluorescence microscopy; host organism interaction; human tissue; hydropathy; inflammation; leukocyte activation /transformation; leukocyte adhesion molecules; neutrophil; phagocytosis; polyurethanes; protein structure; thiols; video microscopy

DESCRIPTION: Two hundred million intravascular devices are sold annually in the United States and it is clear that biomaterial devices are an intricate part of clinical medicine. Bacterial infection, inflammation, and thrombosis are major complications involved with all types of blood contacting intravascular devices, ranging from catheters to artificial hearts. It has been estimated that over 45% of hospital infections are related to implants in medical devices. These infections do not respond well to conventional antibiotic therapy and often necessitate removal of the implant. Little is known concerning the specific mechanisms that govern the complex relationship between infection and inflammation. Factors that may affect this relationship are the surface chemistry of bacteria, blood cells, and the artificial surface as well as surface adsorbed proteins. In addition, the adhesion and metabolism of bacteria and the behavior of adherent neutrophils are important factors. The focus of the proposed research is to investigate the cellular adhesion and activation events that occur during infection and inflammation on synthetic biomaterial surfaces in an experimental setting. In addition, the investigators propose to determine the influence of surface chemistry in these events. The relationship between device centered infection and the host immune response will be investigated by examining the adhesion, activation, accompanying morphological changes, phagocytosis, and killing ability of PMNs in the presence of adherent bacteria on artificial surfaces. These studies will be primarily carried out using an automated video microscopy system with digital image processing that allows the direct observation of individual cells interacting with surfaces over time. The influence of adsorbed proteins on these interactions and how they are affected by the material surface will be examined on polyurethanes which contain pendant sulfanate, quaternary amine, alkyl, or phosphonate groups. The effects of surface chemistry charge, and hydrophobicity on bacterial adhesion and colonization and the bacterial host defense of PMNs will be determined using self assembled monolayer (SAM) surfaces with highly order, specific chemistry. SAMs will be synthesized with various functionalities including ethylene oxide, phosphorylcholine, and the Arg-Gly-Asp peptide sequence. This study aims at elucidating the mechanisms of bacterial attachment to synthetic biomaterials by utilizing surfaces with which it is possible to achieve molecular level control. The information obtained will provide a better understanding of the inter-relationship between biomaterial mediated bacterial infection and inflammation. A detailed understanding of these mechanisms will lead to the development of biomaterials that are resistant to microbial adhesion and proliferation while supporting natural host defense mechanisms.

描述：美国每年售出2亿个血管内装置 显然，生物材料设备是一种错综复杂的 临床医学的一部分。细菌感染、炎症和 血栓形成是各种类型血液的主要并发症。 接触血管内装置，从导管到人造血管 红心。据估计，超过45%的医院感染是 与医疗设备中的植入物有关。这些感染没有反应 对传统的抗生素治疗很好，而且经常需要移除 植入。关于管理的具体机制我们知之甚少 感染和炎症之间的复杂关系。可能存在的因素 影响这种关系的是细菌、血细胞的表面化学， 人工表面以及表面吸附的蛋白质。在……里面 此外，细菌的黏附和代谢以及细菌的行为 粘附性中性粒细胞是重要因素。建议的重点是 研究的目的是调查细胞黏附和激活事件 发生在合成生物材料表面的感染和炎症期间 这是一个实验性的场景。此外，调查人员建议 确定表面化学在这些事件中的影响。这个 设备中心感染与宿主免疫反应的关系 将通过检查粘连、激活、伴随进行调查 外周血中中性粒细胞的形态变化、吞噬功能和杀伤能力 人造表面上附着细菌的存在。这些研究将是 主要使用自动视频显微镜系统进行， 数字图像处理，允许直接观察个体 随着时间的推移，细胞与表面相互作用。吸附对环境的影响 蛋白质在这些相互作用中的作用以及它们如何受到材料的影响 表面将在含有侧链磺酸盐的聚氨酯上进行检查， 季胺、烷基或膦酸基。表面的影响 化学电荷和疏水性对细菌黏附和定植的影响 而PMN的细菌宿主防御能力将用SELF确定 具有高度有序、特定化学成分的组装单分子层(SAM)表面。 SAMS将被合成具有包括乙烯在内的各种功能 氧化物、磷胆碱和Arg-Gly-Asp肽序列。本研究 旨在阐明细菌在合成材料上的附着机制。 利用表面可以实现的生物材料 分子水平控制。所获得的信息将提供更好的 对生物材料中介的相互关系的认识 细菌感染和炎症。对这些内容的详细了解 机制将导致具有抗性的生物材料的发展 在支持自然宿主的同时促进微生物的黏附和增殖 防御机制。