Effect of microdomain structures on the enzyme induced hydrolytic degradation of polycarbonate-urethanes

grantor: University of TorontoPolycarbonate urethanes (PCNUs) have been used as a replacement for traditional biomedical polyether-urethanes due to their enhanced resistance to oxidative biodegradation. However, relatively little is known about their hydrolytic stability in the presence of inflammatory derived enzymes. This has in part motivated the work of this thesis, which probes the nature of the cholesterol esterase (CE) catalyzed hydrolytic degradation processes in PCNUs. A series of model PCNUs with different micro-domain structures were synthesized, by changing their hard segment size and chemistry. The polymer bulk structures were characterized with gel permeation chromatography (GPC), differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR) for their bulk structures. The surface properties of the polymers were analyzed with contact angle, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). 14C-labelled PCNUs were incubated with different CE concentrations, for a period of ten weeks (pH 7.0 at 37°C), and radiolabel counting was used to monitor the degradation. The nature of the degradation products was assessed by high performance liquid chromatography (HPLC) and mass spectrometry (MS). The results showed that all of the PCNUs synthesized in this study were susceptible to CE catalyzed hydrolytic degradation, and that the extent of degradation was highly dependent on the nature of hard segment interactions in the polymer and at the surface. The nature of the degradation process was defined by the following features, (1) the amount of each group located at the surface and at the interface of the soft/hard segments, (2) the crystallinity of the hard segments and, (3) the degree of hydrogen bonding between the carbonate and urethane groups, as well as the inter-urethane groups. The latter factor appeared to be most influential. Despite its relative stability, the MDI based polymer was the only material which produced a diamine product (i.e. methylene diamine, MDA). The findings have important implications in defining a clear understanding of biostability for biomedical polyurethanes, specifically at the molecular level, and in describing the manner by which the body's enzymes disassemble these macromolecules over time.Ph.D