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Polycarbonate-urethane hard segment type influences esterase substrate specificity for human-macrophage-mediated
Rosalind S Labow1, Danne Sa, Loren A Matheson
1University of Ottawa Heart Institute, University of Ottawa, ON, Canada. rlabow@ottawaheart.ca
Journal of Biomaterials Science. Polymer Edition
|October 20, 2005
Summary
The type of diisocyanate in polycarbonate-based polyurethanes influences degradation by macrophages. Different esterases contribute to material breakdown, depending on the polyurethane chemistry and cellular response.
Area of Science:
- Biomaterials Science
- Cell Biology
- Biochemistry
Background:
- Esterase activity is known to degrade polyurethanes (PUs).
- Monocyte-derived macrophages (MDM) synthesize and secrete esterases like cholesterol esterase (CE) and monocyte-specific esterase (MSE).
- Polycarbonate-based PUs (PCNUs) can be synthesized with different diisocyanates, such as hexane diisocyanate (HDI) and 4,4'-methylene-bis-phenyl diisocyanate (MDI).
Purpose of the Study:
- To investigate how different diisocyanate chemistries in PCNUs affect degradation mediated by MDM.
- To determine the specific roles of CE and MSE in the degradation of PCNUs with varying diisocyanate components.
- To compare the effects of esterase inhibitors and stimulators on PCNU degradation and esterase activity.
Main Methods:
- MDM were cultured on PCNUs synthesized with HDI (HDI321) or MDI (MDI321).
- Degradation was measured by radiolabel release (RR).
- The effects of phenylmethylsulfonyl fluoride (PMSF), sodium fluoride (NaF), and sodium taurocholate (NaT) on RR and esterase activity were assessed.
Main Results:
- Sodium fluoride (NaF) inhibited both carboxyl esterase (CXE)- and MDM-mediated RR similarly for both PCNU types.
- MDM-mediated RR from MDI321 was significantly higher (1.8-fold) than from HDI321 when stimulated with sodium taurocholate (NaT) (P = 0.005).
- This suggests differential contributions of CE and MSE to the degradation of HDI- and MDI-based PCNUs.
Conclusions:
- Diisocyanate chemistry in PCNUs plays a crucial role in determining the extent and mechanism of their degradation by macrophages.
- The substrate specificity of esterases and the cellular induction of specific esterase synthesis influence biomaterial degradation.
- Understanding these interactions is key for designing more stable or degradable polyurethane-based medical devices.