title: Synthetic alginate is a carrier of OP-1 for bone induction.
abstract: Bone morphogenetic proteins (BMPs) can induce bone formation in vivo when combined with appropriate carriers. Several materials, including animal collagens and synthetic polymers, have been evaluated as carriers for BMPs. We examined alginate, an approved biomaterial for human use, as a carrier for BMP-7. In a mouse model of ectopic bone formation, the following four carriers for recombinant human OP-1 (BMP-7) were tested: alginate crosslinked by divalent cations (DC alginate), alginate crosslinked by covalent bonds (CB alginate), Type I atelocollagen, and poly-D,L-lactic acid-polyethyleneglycol block copolymer (PLA-PEG). Discs of carrier materials (5-mm diameter) containing OP-1 (3-30 microg) were implanted beneath the fascia of the back muscles in six mice per group. These discs were recovered 3 weeks after implantation and subjected to radiographic and histologic studies. Ectopic bone formation occurred in a dose-dependent manner after the implantation of DC alginate, atelocollagen, and PLA-PEG, but occurred only at the highest dose implanted with CB alginate. Bone formation with DC alginate/OP-1 composites was equivalent to that with atelocollagen/OP-1 composites. Our data suggest DC alginate, a material free of animal products that is already approved by the FDA and other authorities, is a safe and potent carrier for OP-1. This carrier may also be applicable to various other situations in the orthopaedic field.
authors.affiliation: Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nanno
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Sugiyasu
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Myoui
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009999:Ossification, Heterotopic / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D010012:Osteogenesis / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility
chemical_list: D000464:Alginates; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D004343:Drug Implants; D006603:Hexuronic Acids; D007773:Lactates; D011994:Recombinant Proteins; C059821:atelocollagen; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D020723:Glucuronic Acid; D003094:Collagen; D000469:Alkaline Phosphatase