title: Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers.
abstract: The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues.
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan. saitoko@hsp.md.shinshu-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Horiuchi
authors.forename: H
authors.initials: H
authors.lastname: Ota
authors.forename: J
authors.initials: J
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Nawata
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Nozaki
authors.forename: K
authors.initials: K
authors.lastname: Takaoka
mesh_terms: D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D024042:Collagen Type I / Q000008:administration & dosage; D004337:Drug Carriers; D006801:Humans; D007773:Lactates / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D010012:Osteogenesis; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011161:Porifera; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D004337:Drug Carriers; D007773:Lactates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C088513:poly(lactic acid-ethylene glycol); C499469:recombinant human bone morphogenetic protein-2; D011092:Polyethylene Glycols