title: Bone regeneration by recombinant human bone morphogenetic protein-2 and a novel biodegradable carrier in a rabbit ulnar defect model.
abstract: The effects of recombinant human bone morphogenetic protein (rhBMP)-2 and a novel carrier, PLGA-coated gelatin sponge (PGS), on bone defect repair was examined. A 1.5 cm unilateral segmental bone defect was created in the ulnar diaphysis of a Japanese white rabbit. In an initial study, defects were either treated with PGS impregnated with various concentrations of rhBMP-2 (0, 0.1, 0.4 and 1 mg/cm(3)) or left untreated. Defect healing was assessed by radiographic union rate, and biomechanical properties of regenerated bones were determined at 16 weeks postoperatively. In a second study, defects were implanted with PGS with or without rhBMP-2, and histologically observed at postoperative weeks 8 and 16. Radiographic union rate increased the dose-dependently at an early time point. All defects treated with rhBMP-2 (0.4 and 1 mg/cm(3)) were radiographically repaired. Mechanical properties of regenerated bones were restored in a dose-dependent manner. Neither ulnae left untreated nor implanted PGS alone showed radiographic union. Longitudinal alignment of lamellar structure was observed histologically at 16 weeks, indicating that remodeling of regenerated bone was complete. Implanted PGS was almost completely resorbed by 8 weeks, and no abnormalities were observed in the surrounding soft tissue. These results suggest that PGS is a promising carrier for rhBMP-2.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki, Japan. kokubo@yamanouchi.co.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokubo
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Fujimoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Yokota
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nozaki
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyata
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics*; D001673:Biodegradation, Environmental; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology*; D005780:Gelatin; D006801:Humans; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D014457:Ulna / Q000187:drug effects / Q000293:injuries*
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin