title: Responses in vivo to purified poly(3-hydroxybutyrate-co-3-hydroxyvalerate) implanted in a murine tibial defect model.
abstract: Effective bone biomaterials provide structural support for bone regeneration and elicit minimal inflammatory or toxic effects in vivo. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a bacterially derived biodegradable polymer that possesses suitable mechanical strength for use as a bone biomaterial and has a slow rate of degradation in biological environments. Our previous in vitro study showed that many PHBV preparations are contaminated with bacterial lipopolysaccharide, and we developed a purification procedure to substantially remove it. Here, we have evaluated the in vivo biocompatibility of PHBV purified by H(2)O(2) treatment and solvent extraction. We utilized a murine tibial defect model consisting of a hole drilled through the diameter of the tibial diaphysis into which nonporous cylindrical plugs of purified PHBV were implanted. The animals were sacrificed at 1 week and 4 weeks postsurgery, and tibiae were examined using histological staining. The PHBV implant induced a mild inflammatory response 1 week after injury, which persisted for 4 weeks. Granuloma type tissues formed only when the implant protruded into the overlaying tissue. Woven bone formation occurred adjacent to the implant, which gave rise to lamellar bone and stabilized the implant indicating that the PHBV did not affect this process. Our data validated the murine defect model and indicate that solid PHBV induces a mild tissue reaction with bone deposition adjacent to the implant with no fibrous tissue present at 4 weeks post surgery.
authors.affiliation: Institute for Molecular Bioscience and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Ck A
authors.initials: CA
authors.lastname: Wu
authors.forename: A R
authors.initials: AR
authors.lastname: Pettit
authors.forename: S
authors.initials: S
authors.lastname: Toulson
authors.forename: L
authors.initials: L
authors.lastname: Grøndahl
authors.forename: E J
authors.initials: EJ
authors.lastname: Mackie
authors.forename: A I
authors.initials: AI
authors.lastname: Cassady
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry*; D001861:Bone Regeneration; D018786:Bone Substitutes; D001842:Bone and Bones / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009092:Mucous Membrane / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry*; D019736:Prostheses and Implants; D012997:Solvents / Q000737:chemistry; D013977:Tibia / Q000378:metabolism*; D000094122:Polyhydroxybutyrates
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D006861:Hydrogen Peroxide; D008070:Lipopolysaccharides; D011091:Polyesters; D012997:Solvents; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates