title: Reduction of the in vitro pro-inflammatory response by macrophages to poly(3-hydroxybutyrate-co-3-hydroxyvalerate).
abstract: This study evaluates the pro-inflammatory response to the thermoplastic biopolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) through the analysis of cellular responses in vitro. The murine macrophage RAW264.7 cell line was cultured on solvent cast PHBV films, which was found to induce pro-inflammatory activity that required direct contact between the material and the macrophages. The identity of the pro-inflammatory stimulus was determined by culturing bone marrow-derived macrophages from bacterial lipopolysaccharide (LPS) hyporesponsive C3H/HeJ mice and CpG non-responsive TLR9-/- mice on PHBV. The lack of a pro-inflammatory response by the C3H/HeJ cells indicates that the pro-inflammatory agent present within PHBV is predominately LPS while the TLR9-/- macrophages confirmed that CpG-containing bacterial DNA is unlikely to contribute to the activity. A series of purification procedures was evaluated and one procedure was developed that utilized hydrogen peroxide treatment in solution. The optimized purification was found to substantially reduce the pro-inflammatory response to PHBV without adversely affecting either the molecular structure or molecular weight of the material thereby rendering it more amenable for use as a biomaterial in vivo.
authors.affiliation: Institute for Molecular Bioscience and Co-operative Research Centre for Chronic Inflammatory Diseases, The University of Queensland, ST LUCIA 4072, Australia.
authors.forename: Andy C K
authors.initials: AC
authors.lastname: Wu
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Grøndahl
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Jack
authors.forename: Michelle X
authors.initials: MX
authors.lastname: Foo
authors.forename: Matt
authors.initials: M
authors.lastname: Trau
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
authors.forename: Alan I
authors.initials: AI
authors.lastname: Cassady
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011091:Polyesters / Q000737:chemistry*; D000094122:Polyhydroxybutyrates
chemical_list: D001672:Biocompatible Materials; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D011091:Polyesters; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates