The proposed research program is an extension of current studies directed toward a fundamental understanding of biocompatibility and biostability of biomedical elastomers, specifically polyurethanes. The overall objective is to test the proposed hypothesis for the biodegradation of implanted poly(etherurethanes) (PEUs) which involves cell/polymer feedback mechanism. The Initial adsorption of proteins affects the subsequent cellular adhesion and activation. The latter may be followed by a respiratory burst which produces oxygen species that are most likely responsible for oxidative degradation of the polymer chain. The altered surface properties and degradation products may further affect the process of protein adsorption and/or cell adhesion and activation via feedback mechanisms. Simultaneously, the exocytosis of lysosomal enzymes and other mediators may cause other cells to become activated. In order to confirm and/or modify the hypothesis and to establish operative mechanisms, experimental procedures will be carried out on PEUs of known composition, with and without specific additives to enhance biostability. Experimental procedures are proposed to: 1) Determine the adsorption of human blood plasma proteins to candidate PEUs using radioimmunoassay (RIA) or immunogold protein A labelling with scanning electron microscopy (SEM); 2) Quantitatively measure cell adhesion and activation using the cage implant system; 3) Characterize surface 'corrosion' of implanted PEUs using optical microscopy (OM) and SEM, identify chemical changes by ATR-FTIR and GPC analysis of extracts, and determine the effects on performance properties including fatigue resistance; 4) Assess monocyte respiratory burst mediated PEU degradation in vitro with the monocyte/macrophage culture system; and 5) Establish the chemistry of oxidative degradation of PEUs in vitro using metal- catalyzed peroxide treatment and accelerated conditions.
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