Changes in macrophage function and morphology due to biomedical polyurethane surfaces undergoing biodegradation.
Monocytes are recruited to the material surface of an implanted biomedical device recognizing it as a foreign body. Differentiation into macrophages subsequently occurs followed by fusion to form foreign body giant cells (FBGCs). Consequently, implants can become degraded, cause chronic inflammation or become isolated by fibrous encapsulation. In this study, a relationship between material surface chemistry and the FBGC response was demonstrated by seeding mature monocyte-derived macrophages (MDMs) on polycarbonate-based polyurethanes that differed in their chemical structures (synthesized with poly(1,6-hexyl 1,2-ethyl carbonate) diol, and either (14)C-hexane diisocyanate and butanediol (BD) (referred to as HDI) or 4,4'-methylene bisphenyl diisocyanate and (14)C-BD (referred to as MDI)) and material degradation assessed. At 48 h of cell-material interaction, the FBGC attached to HDI were more multinucleated (73%) compared to MDI or the polystyrene (PS) control (21 and 36%, respectively). There was a fivefold increase in the synthesis and secretion of a protein with an approximate molecular weight of 48 kDa and a pI of 6.1 (determined by two-dimensional gel electrophoresis) only from cells seeded on HDI. Immunoprecipitation confirmed that MSE and CE were synthesized and secreted de novo. Immunoblotting also showed an increase in secreted monocyte-specific esterase (MSE) and cholesterol esterase (CE) from cells seeded on HDI relative to PS and MDI. Significantly more radiolabel ((14)C) release and esterase activity were elicited by MDMs on HDI than MDI (P < 0.05). The material that was more degradable (HDI), elicited greater protein synthesis and esterase secretion as well as more multinucleated MDMs than MDI, suggesting that the material surface chemistry modulates the function of MDM at the site of an inflammatory response to an implanted device.
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Loren A
LA
Matheson
J Paul
JP
Santerre
Rosalind S
RS
Labow
D020341:Absorbable Implants / Q000009:adverse effects; D003485:Cyanates / Q000378:metabolism / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004950:Esterases / Q000096:biosynthesis; D015743:Giant Cells, Foreign-Body / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D017953:Isocyanates / Q000378:metabolism / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D011140:Polyurethanes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011233:Precipitin Tests; D002787:Sterol Esterase / Q000096:biosynthesis; D013499:Surface Properties; D020298:U937 Cells; D001559:Benzhydryl Compounds
D003485:Cyanates; D004950:Esterases; D017953:Isocyanates; D011140:Polyurethanes; D002787:Sterol Esterase; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds; C413962:monocyte-specific esterase