Development of a mathematical model describing the enzymatic degradation of biomedical polyurethanes. I: Background, rationale and model formulation

Of the various polymers used in medical devices, polyurethanes have been relatively successful due to their acceptable mechanical and biological properties. However, concerns have arisen in recent years regarding the biostability of polyurethanes when exposed to the harsh environment of the human body. Lysosomal enzymes released from inflammatory cells have been proposed as important mediators in the degradation of biomedical polyurethanes. If polyurethanes are to be developed which resist the rigors of implantation, a clear understanding of the degradative processes will be required. Unfortunately, the exact mechanism of enzymatic degradation of polyurethanes remains poorly defined. Consequently, a computer model was proposed as a tool for elucidating, simulating 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 vitro degradation of a poly(ester-urea-urethane) by a single hydrolytic enzyme, cholesterol esterase. The processes of polyurethane surface dynamics, enzyme adsorption and inactivation, solvolytic and enzymatic degradation of the polyurethane, and degradation of products were also proposed. Parameter values and starting conditions were estimated from existing literature and the model was solved for various conditions which were considered experimentally relevant. Factors such as the rate of enzyme inactivation, the susceptibility of specific polyurethane bonds, the rates of in-solution degradation and the mobility of the polyurethane surface all had a marked effect on the extent of degradation and the type and amount of breakdown products in solution. Model development and preliminary simulations are presented.