title: Polycarbonate-urethane hard segment type influences esterase substrate specificity for human-macrophage-mediated biodegradation.
abstract: Previous studies have shown that esterase activity can degrade a variety of polyurethanes (PUs), including polycarbonate-based PUs (PCNUs). When cultured on PCNUs, differing in their chemistries, monocyte-derived macrophages (MDM) synthesized and secreted different amounts of both cholesterol esterase (CE) and monocyte-specific esterase (MSE). MDM were seeded on PCNUs synthesized with hexane diisocyanate (HDI) or 4,4'-methylene-bis-phenyl diisocyanate (MDI), PCN and [14C]butanediol (BD) in the ratio 3:2:1 (referred to as HDI321 or MDI321). The effect of phenylmethylsulfonyl fluoride (PMSF, a serine esterase and proteinase inhibitor), sodium fluoride (NaF, a MSE inhibitor) and sodium taurocholate (NaT, a CE stimulator) was assessed on degradation (measured by radiolabel release (RR)) and esterase activity in MDM lysate. The results were compared to the effect that these reagents had on commercially available CE and carboxyl esterase (CXE), which has a specificity similar to MSE. NaF inhibited CXE- and MDM-mediated RR to the same extent as for both PCNUs. However, the MDM-mediated RR from MDI321 was 1.8-times higher than HDI321 in the presence of NaT (P = 0.005). This study suggests that the difference in diisocyanate chemistry may dictate the relative contribution of each esterase to a specific material's degradation. This may be related to both the substrate specificity of each esterase, as well as by the relative amount of each esterase that the specific biomaterial substrates induce the cells to synthesize and secrete.
authors.affiliation: University of Ottawa Heart Institute, University of Ottawa, ON, Canada. rlabow@ottawaheart.ca
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Labow
authors.forename: Danne
authors.initials: D
authors.lastname: Sa
authors.forename: Loren A
authors.initials: LA
authors.lastname: Matheson
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001673:Biodegradation, Environmental; D002478:Cells, Cultured; D004950:Esterases / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D008422:Materials Testing; D011076:Polycarboxylate Cement / Q000737:chemistry / Q000378:metabolism*; D011140:Polyurethanes / Q000737:chemistry / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001672:Biocompatible Materials; D011076:Polycarboxylate Cement; D011140:Polyurethanes; C005506:polycarbonate; D004950:Esterases; C413962:monocyte-specific esterase; D002787:Sterol Esterase