title: Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase.
abstract: Growth factor delivered with implantable biomaterials has been used to both accelerate and ensure healing of open fractures in human patients. However, a major limitation of implantable biomaterials is the requirement for open surgical placement. Here, we developed an injectable collagen material-based bone formation system consisting of injectable collagen powder with fibril morphology and collagen triple helix conformation, and basic fibroblast growth factor (bFGF) fused to the collagen-binding domain (CBD) of Clostridium histolyticum collagenase. The affinity of the CBD towards collagen was confirmed by the results of collagen-binding assays. Moreover, the combination of the collagen binding-bFGF fusion protein (CB-bFGF) with injectable collagen powder induced bone formation at protein concentrations lower than those required for bFGF alone in mice fracture models. Taken together, these properties suggest that the CB-bFGF/collagen powder composite is a promising injectable material for bone repair in the clinical setting.
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Kanagawa, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Saito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Uchida
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsushita
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nishi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ogura
authors.forename: Shunji
authors.initials: S
authors.lastname: Hattori
authors.forename: Hisako
authors.initials: H
authors.lastname: Fujimaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Takaso
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000033:anatomy & histology / Q000187:drug effects; D003013:Clostridium / Q000201:enzymology*; D003094:Collagen / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D003012:Microbial Collagenase / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D003012:Microbial Collagenase
keywords: Basic fibroblast growth factor; collagen-binding domain; collagenase; fracture healing; injectable collagen power