Hydrolytic degradation of poly(carbonate)-urethanes by monocyte-derived macrophages

Polycarbonate (PCN)-based polyurethanes (PCNU) are rapidly becoming the cho sen polyurethane (PU) for long-term implantation since they have shown decr eased susceptibility to oxidation. However, monocyte-derived macrophages (M DM), the cell implicated in biodegradation, also contain hydrolytic activit ies. Hence, in this study, an activated human MDM cell system was used to a ssess the biostability of a PCNU, synthesized with C-14-hexane diisocyanate (HDI) and butanediol (BD), previously shown to be susceptible to hydrolysi s by cholesterol esterase (CE). Monocytes, isolated from whole blood and cu ltured for 14 days on polystyrene (PS) to mature MDM, were gently trypsiniz ed and seeded onto C-14-PCNU. Radiolabel release and esterase activity, as measured with p-nitrophenylbutyrate, increased for almost 2 weeks. At 1 wee k, the increase in radiolabel release and esterase activity were diminished by more than 50% when the protein synthesis inhibitor, cycloheximide, or t he serine esterase/protease inhibitor, phenylmethylsulfonylfluoride was add ed to the medium. This strongly suggests that in part, it was MDM esterase activity which contributed to the PU degradation. In an effort to simulate the potential combination of oxidative and hydrolytic activities of inflamm atory cells, C-14-PCNU was exposed to HOCl and then CE. Interestingly, the release of radiolabeled products by CE was significantly inhibited by the p re-treatment of PCNU with HOCl The results of this study show that while th e co-existing roles of oxidation and hydrolysis in the biodegradation of PC NUs remains to be elucidated, a clear relationship is drawn for PCNU degrad ation to the hydrolytic degradative activities which increase in MDM during differentiation from monocytes, and during activation in the chronic phase of the inflammatory response. (C) 2001 Elsevier Science Ltd. All rights re served.