Interrelations Between Bacterial Infection, Inflammation, and Thrombosis on Biomedical Devices

9632568库珀临床感染是与合成植入设备相关的最大问题之一。这类感染占医院感染的45%以上，与留置导管、关节置换手术和搭桥手术有关。这类感染也比传统感染更难治疗。由于血管内设备每年的销量超过2亿台，很明显，与生物医学设备相关的感染在临床医学中构成了一个巨大的问题。了解导致此类感染的细菌附着在植入物上并抵抗抗生素治疗的机制，是开发抵抗细菌生长的材料和改进植入物相关感染治疗的重要一步。塑料植入物的使用不仅与感染的风险有关，而且还与血栓形成(血栓形成)和部位周围的炎症有关。人们对控制感染、炎症和血栓形成之间复杂关系的具体机制知之甚少。可能影响这种关系的因素包括设备的表面化学，植入后可能从血液中吸收的蛋白质，以及细菌和血细胞的表面化学。这项研究的重点将是调查感染、炎症和血栓形成所共有的细胞黏附和激活事件，并确定它们对其他过程的单独影响。具体地说，将研究血栓的蛋白质和细胞成分(例如纤维蛋白和血小板)在介导细菌在人造表面上的黏附和定植方面的影响。此外，还将研究黏附细菌对血小板黏附和激活的影响。另一个需要研究的重要因素是血栓和植入物表面附着细菌代谢状态的变化。我们将研究细菌附着在化学修饰的聚氨酯上时，白细胞的黏附、激活和伴随的形态变化。这些研究将主要使用自动化视频显微镜系统进行，该系统允许在一段时间内直接观察单个细胞与不同表面的相互作用。细胞-表面相互作用的研究将在玻璃和聚氨酯表面以及自组装单分子膜的模型表面上进行。在这项工作中获得的信息将提供更好的了解植入装置、细菌感染、炎症和血栓形成之间的相互关系，以及每个过程如何影响另一个过程。对控制这些关系的机制的详细了解将导致抗微生物黏附、增殖和血栓形成的生物材料的开发。归根结底，这样的研究对改善患者福利和降低医疗成本具有重要意义。***

9632568 Cooper Clinical infections are one of the greatest problems associated with synthetic implanted devices. Such infections account for more than 45% of hospital infections, associated with indwelling catheters and surgery for joint replacement, and bypass operations. Such infections are also more difficult to treat than conventional infections. With over 200 million intravascular devices sold annually, it is clear that infections associated with biomedical devices pose a huge problem in clinical medicine. Understanding the mechanisms by which the bacteria responsible for such infections adhere to implants and resist antibiotic treatment is an important step in developine materials that resist bacterial growth, and improving therapy for implant-associated infections. The use of plastic materials for implants is not only associated with risk of infection, but also risk of clot formation (thrombosis), and inflammation around the site. Little is known about the specific mechanisms that govern the complex relationships between infections, inflammation, and thrombosis. Factors that may affect this relationship are the surface chemistry of the device, the proteins that may be absorbed from the blood after implantation, and the surface chemistry of the bacteria and blood cells. The focus of this research will be to investigate the cellular adhesion and activation events that infection, inflammation, and thrombosis have in common, and to determine their individual effects on the other processes. Specifically, the influence that protein and cellular components of thrombi (e.g. fibrin and blood platelets) have in mediating bacterial adhesion and colonization on artificial surfaces will be investigated. The effects of adherent bacteria on platelet adhesion and activation will also be studied. Another important factor that will be investigated is the change in the metabolic state of adherent bacteria on thrombi and on implant surfaces. The adhesion, activa tion, and accompanying shape changes of white blood cells in the presence of adherent bacteria on chemically modified polyurethanes will be studied. These studies will primarily be carried out using an automated viedomicroscopy system that allows the direct observation of individual cells interacting with different surfaces over a period of time. The study of cell-surface interactions will be carried out on both glass and polyurethane surfaces, as well as model surfaces of self-assembling monolayers. The information obtained in this work will provide a better understanding of the interrelationship between implanted devices, bacterial infection, inflammation, and thrombosis, an how each process may influence the other. Detailed understanding of the mechanisms that govern these relationships will lead to the development of biomaterials that resist microbial adhesion and proliferation as well as thrombosis. Ultimately, studies such as these are important in improving patient welfare and reducing health care costs. ***