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

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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. ***