In many instances, for example vascular prosthesis, it is the long- term performance of polymeric biomaterials that will determine their clinical usefulness. Advances in the development of improved biomaterials and in the understanding of the mechanisms of arti- ficial surface-induced thrombogenesis must include the assessment of those factors which influence long-term biocompatibility. We propose to use a chronic canine ex vivo shunt technique developed in our laboratory to investigate the influence of polymeric material surface and bulk properties on long-term blood compatibility. Data obtained in the chronic model, will be correlated with that previously obtained for similar materials used in our acute canine ex vivo experiments. As an adjunct to thrombogenicity (platelet activation, platelet deposition etc.) as a description of blood compatibility, we will use the chronic model in studies where patency/failure is the endpoint determinant of biocompatibility. Various flow rates and durations of exposure to blood contact will be used to test material performance in conditions which are possibly more clinically relevant. Chronic ex vivo experiments will provide information on the desorption and exchange of radiolabeled plasma proteins on polymer surfaces over periods in excess of the two hour limit imposed by the acute model. The role of passivating proteins (e.g. albumin and transferrin) in long-term blood exposure will be explored. The effect of endothelial cell seeding on the long-term biocompatibility of polymeric materials will be evaluated in terms of thromboresistance and patency/failure rates in the chronic ex vivo model. These studies will be correlated with in vitro studies of polymer surface-protein-endothelial cell interactions. The biodegradation of polymer surfaces that may occur during long-term blood contact, will be evaluated by post implant bulk and surface characterization techniques such as Gel permeation chromatography, dynamic mechanical testing. Fourier Transform Infrared Spectroscopy with attenuated total Reflectance (FTIRATR), scanning electron microscopy, and x-ray photoelectron spectroscopy. In vitro studies using single and multi-component enzyme mixtures and lipid/enzyme mixtures will attempt to elucidate the pathways involved in the biodegradation of medical grade polymers and modified polyurethanes. These studies will lead to a better understanding of the mechanisms involved in artificial surface-induced thrombogenesis and will aid in the design of biocompatible polymeric materials.
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