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.
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