The biodegradation of poly(urethane)s by the esterolytic activity of serine proteases and oxidative enzyme systems

Biodegradation of poly(urethane)s (PU)s using single enzymes in vitro was a ssessed by measuring radiolabel release from model poly(ester-urea-urethane ) (PESU) and poly(ether-urea-urethane) (PETU) materials synthesized with C- 14-labelled monomers. Cholesterol esterase (CE), an enzyme found in monocyt e-derived macrophages (MDM), has been reported to cause a significant level of radiolabel release from both of these PUs. Previous work has shown that CE activity could be inhibited by the serine protease / esterase inhibitor ; phenylmethylsulfonyl fluoride. Since many serine proteases are present in circulating blood and can be released by cells other than MDM, this study investigated the ability of serine proteases relative to that of CE to caus e the degradation of PUs. In addition, the possible role of several oxidati ve enzymes in the breakdown of PUs was investigated. Proteinase K, chymotry psin and thrombin. when incubated with PESU, coated on glass slips, caused significant radiolabel release, with proteinase K giving the highest values . However, the highest radiolabel release which proteinase K could elicit w as ten times less than CE. Thrombin and then chymotrypsin were progressivel y worse in their biodegradative activity. Only CE, and not the serine prote ases, could elicit a detectable radiolabel release from PETU. Although the release of reactive oxygen species and molecular oxygen occur around an imp lanted biomaterial, several oxidative systems (peroxidase, xanthine oxidase , catalase), known to produce one or more of these molecular species, were unable to induce radiolabel release from these PUs. The process of biodegra dation as assessed by radiolabel release appears to be a specific hydrolyti c process, while the role of oxidative enzymes remains less clear.