The combination of outstanding physical and chemical properties of polyurethanes (PUs) coupled with their biocompatibility have led to their use in a wide range of biomedical applications. In the last decade, concerns regarding the biostability of PUs were raised when some PU pacemaker leads were shown to undergo environmental stress-cracking in humans. Current studies in this laboratory directed toward a fundamental understanding of biocompatibility and biostability of PU elastomers have led to a hypothesis for the cell/polymer feedback control of in vivo biodegradation. In order to confirm and/or modify the hypothesis, experimental procedures will be carried out on PUs of known composition with and without specific additives that enhance biostability.
The specific aims of the proposed research are: 1) To elucidate the chemical mechanisms by which cellular degrading agents (radicals, HOCl, acid)- cause hydrolytic and/or oxidative chain cleavage of polyetherurethanes, and other PUs with non-polyether soft segments where the mechanism(s) of biodegradation may be different. Correlative studies will be made with accelerated in Vitro conditions that mimic the in Vivo environment. 2) To characterize the surface degradation after in Vivo and in Vitro exposure, and correlate the results with the effect on performance properties. Methods of material characterization will include attenuated total reflectance infrared spectroscopy, photoacoustic infrared spectroscopy, ESCA, contact angle, gel permeation chromatography, scanning electron microscopy and scanning acoustic microscopy. 3) To ascertain the effect of stress and strain state on the rate of PU biodegradation. The effects of uniaxial and biaxial strain will be examined in vivo and in vitro, and the results will be correlated with creep and fatigue behavior as determined in vitro under oxidative and hydrolytic conditions. 4) To determine the effect of PU surface chemistry and the effect of additives on the adhesion of polymorphonuclear leukocytes and monocytes/macrophages under static and dynamic conditions, with and without the presence of complement. These studies will be correlated with in vivo experiments to examine the effects of antioxidants and macrophage inhibitors on biodegradation.
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