title: Long-term stability of bone tissues induced by an osteoinductive biomaterial, recombinant human bone morphogenetic protein-2 and a biodegradable carrier.
abstract: The long-term stability of bone tissues induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) and poly[L-lactide-co-glycolide] copolymer-coated gelatin sponge (PGS) was examined. In 16 dogs, 2.5 cm unilateral bone defects were created in the left tibial diaphyses. Tibia was fixed with metal plate, and PGS impregnated with (0.4 mg/cm(3)) or without rhBMP-2 was implanted into 15 or one defects, respectively. The metal plates of rhBMP-2-treated limbs were removed 16 weeks after the implantation. The bilateral tibiae of five animals each of the rhBMP-2-treated group were harvested at 32, 52 or 104 weeks, and served for biomechanical testing and histology. Although the defect that received PGS alone resulted in nonunion at 16 weeks, all defects treated with rhBMP-2 achieved radiographic bony union by 8 weeks. Biomechanical properties of the regenerated bones restored to the levels of intact tibiae at 32 weeks, but torsional stiffness was significantly higher. No statistical significances were detected in all parameters between regenerated and intact tibiae at 104 weeks. No radiographic and histological findings suggesting enhanced resorption to the regenerated bones were observed. These results suggest the long-term stability of the bone tissues induced by rhBMP-2, and the usefulness of rhBMP-2-impregnated PGS as a biomaterial for long bone defect filling.
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: Manabu
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Teruo
authors.initials: T
authors.lastname: Ito
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nozaki
authors.forename: Takaya
authors.initials: T
authors.lastname: Iwai
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shoji
authors.initials: S
authors.lastname: Yokota
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyata
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects*; D016025:Bone Transplantation / Q000379:methods*; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage; D005500:Follow-Up Studies; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology*; D019344:Lactic Acid; D008297:Male; D008422:Materials Testing; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013718:Tensile Strength; D013978:Tibial Fractures / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid