DEVELOPMENT OF A MATHEMATICAL-MODEL DESCRIBING THE ENZYMATIC DEGRADATION OF BIOMEDICAL POLYURETHANES .1. BACKGROUND, RATIONALE AND MODEL FORMULATION

Of the various polymers used in medical devices, polyurethanes have be en relatively successful due to their acceptable mechanical and biolog ical properties. However, concerns have arisen in recent years regardi ng the biostability of polyurethanes when exposed to the harsh environ ment of the human body. Lysosomal enzymes released from inflammatory c ells have been proposed as important mediators in the degradation of b iomedical polyurethanes. If polyurethanes are to be developed which re sist the rigors of implantation, a clear understanding of the degradat ive processes will be required. Unfortunately, the exact mechanism of enzymatic degradation of polyurethanes remains poorly defined. Consequ ently, a computer model was proposed as a tool for elucidating, simula ting and distinguishing between a variety of mechanisms of degradation . Although the enzymatic environment at the site of an in-vivo implant is very complex, the model was first developed to represent the in-vi tro degradation of a poly(ester-urea-urethane) by a single hydrolytic enzyme, cholesterol esterase. The processes of polyurethane surface dy namics, enzyme adsorption and inactivation, solvolytic and enzymatic d egradation of the polyurethane, and degradation of products in solutio n were all described by the model. Possible breakdown products were al so proposed. Parameter values and starting conditions were estimated f rom existing literature and the model was solved for various condition s which were considered experimentally relevant. Factors such as the r ate of enzyme inactivation, the susceptibility of specific polyurethan e bonds, the rates of in-solution degradation and the mobility of the polyurethane surface all had a marked effect on the extent of degradat ion and the type and amount of breakdown products in solution. Model d evelopment and preliminary simulations are presented.