INFLAMATION AND INFECTION ON BIOMATERIALS

生物材料的炎症和感染

基本信息

批准号：
6343578
负责人：
ERIC KALER
金额：
$ 11.45万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-01-15 至 2003-06-30
项目状态：
已结题

项目摘要

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：每年在美国，很明显，生物材料设备是一种复杂的临床医学的一部分。细菌感染，炎症和血栓形成是所有类型的血液涉及的主要并发症接触血管内设备，从导管到人造心。据估计，超过45％的医院感染是与医疗设备中的植入物有关。这些感染没有反应很好地接受常规的抗生素疗法，通常需要去除注入。关于控制的具体机制，知之甚少感染与炎症之间的复杂关系。可能的因素影响这种关系的是细菌，血细胞，以及人造表面以及表面吸附的蛋白质。在此外，细菌的粘附和代谢和行为粘附的中性粒细胞是重要因素。提议的重点研究是为了研究细胞粘附和激活事件在感染和炎症中发生在合成生物材料表面的炎症中实验环境。此外，调查人员建议在这些事件中确定表面化学的影响。这设备中心感染与宿主免疫反应之间的关系将通过检查粘附，激活，随附的形态学变化，吞噬作用和PMN在在人造表面上存在粘附细菌。这些研究将是主要是使用自动视频显微镜系统进行的数字图像处理可以直接观察个体随着时间的流逝，细胞与表面相互作用。吸附的影响这些相互作用的蛋白质以及它们如何受到材料的影响表面将在包含硫酸吊坠的聚氨酯上检查，第四纪胺，烷基或磷酸基团。表面的影响化学电荷和细菌粘附和定殖的疏水性 PMN的细菌宿主防御将使用自我确定组装的单层（SAM）表面具有高度的特定化学。 SAM将与包括乙烯在内的各种功能合成氧化物，磷酸胆碱和Arg-Gly-App肽序列。这项研究旨在阐明细菌附着与合成的机制生物材料通过利用可以实现的表面分子水平对照。获得的信息将提供更好的了解生物材料介导的相互关系细菌感染和炎症。对这些的详细理解机制将导致抗性生物材料的发展在支持天然宿主的同时，要微生物粘附和增殖国防机制。