The interaction between hydrolytic and oxidative pathways in macrophage‐mediated polyurethane degradation

Abstract Although relatively resistant to oxidation, polycarbonate‐based polyurethanes (PCNUs) are degraded by monocyte‐derived macrophages (MDM) by a co‐mediated mechanism involving both hydrolytic and oxidative pathways. Since a previous study showed that PCNU pretreatment with H₂O₂ modulated degradation by esterases, human MDM were used to further elucidate this dual pathway mechanism of degradation for ¹⁴C‐radiolabeled PCNUs (synthesized with 1,6‐hexane diisocyanate:polycarbonatediol: butanediol with different stoichiometry (HDI431 and HDI321) or another diisocyanate 4,4′‐methylene bisphenyl diisocyanate (MDI321)). Scanning electron microscopy of PCNU slips pretreated with 20% H₂O₂ showed that HDI431 had visible holes with more radiolabel release than from the other PCNUs. When MDM were seeded on H₂O₂‐treated PCNUs, degradation of HDI321 and MDI321, but not HDI431 was decreased. Esterase activity was inhibited in MDM on all surfaces except MDI321, whereas inhibition of acid phosphatase occurred on all surfaces. The material surface itself, induced H₂O₂ release from live MDM, with more H₂O₂ elicited by phorbol myristate acetate treated MDM when cultured on HDI431 but not the other materials. H₂O₂ pretreatment affected cell function by chemically altering the material surface and MDM‐mediated degradation, known to be dependent on surface chemistry. The findings highlight that both oxidative and hydrolytic mechanisms need to be understood in order to tailor material chemistry to produce desired cell responses for in vivo applications. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007