title: The biodegradation of poly(urethane)s by the esterolytic activity of serine proteases and oxidative enzyme systems.
abstract: Biodegradation of poly(urethane)s (PU)s using single enzymes in vitro was assessed by measuring radiolabel release from model poly(ester-urea-urethane) (PESU) and poly(ether-urea-urethane) (PETU) materials synthesized with 14C-labelled monomers. Cholesterol esterase (CE), an enzyme found in monocyte-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 cause the degradation of PUs. In addition, the possible role of several oxidative enzymes in the breakdown of PUs was investigated. Proteinase K, chymotrypsin 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 was ten times less than CE. Thrombin and then chymotrypsin were progressively worse in their biodegradative activity. Only CE, and not the serine proteases, could elicit a detectable radiolabel release from PETU. Although the release of reactive oxygen species and molecular oxygen occur around an implanted 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 biodegradation as assessed by radiolabel release appears to be a specific hydrolytic process, while the role of oxidative enzymes remains less clear.
authors.affiliation: University of Ottawa Heart Institute, ON, Canada. rlabow@ottawaheart.ca
authors.forename: R S
authors.initials: RS
authors.lastname: Labow
authors.forename: E
authors.initials: E
authors.lastname: Meek
authors.forename: J P
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D001673:Biodegradation, Environmental; D004952:Esters / Q000378:metabolism; D006868:Hydrolysis; D010084:Oxidation-Reduction; D011140:Polyurethanes / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004952:Esters; D011140:Polyurethanes; D012697:Serine Endopeptidases