Acceleration of callus formation during fracture healing using basic fibroblast growth factor-kidney disease domain-collagen-binding domain fusion protein combined with allogenic demineralized bone powder

Wataru Saito, Kentaro Uchida, Osamu Matsushita, Gen Inoue, Hiroyuki Sekiguchi, Jun Aikawa, Hisako Fujimaki, Masashi Takaso

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: To repair fractures with large bone defects or gaps, demineralized allogenic bone matrix (DBM) is often applied to the fracture site. However, studies have shown that the use of DBM alone has limited efficacy for repairing fractures. In the present study, we developed an allogenic demineralized bone powder (DBP) with basic fibroblast-derived growth factor containing a polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) from Clostridium histolyticum collagenase (ColH) and investigated the stimulatory effects of bFGF-PKD-CBD combined with allogenic DBP on bone growth in a mouse femur fracture model. Methods: DBP mixed with either phosphate-buffered saline (PBS) (DBP/PBS), 0.58 nmol basic fibroblast growth factor (bFGF) (0.58 nmol DBP/bFGF), 0.058 nmol bFGF-PKD-CBD (0.058 nmol DBP/bFGF-PKD-CBD), or 0.58 nmol bFGF-PKD-CBD (0.58 nmol DBP/bFGF-PKD-CBD) was grafted into fracture sites. Results: bFGF-PKD-CBD/DBP composite accelerates callus formation in a bone fracture model in mice and clearly showed that the composite also increases bone mineral density at fracture sites compared to bFGF/DBP. In addition, bFGF-PKD-CBD/DBP increased callus volume and bone mineral content to similar levels in fractures treated with a tenfold higher amount of bFGF at 4 weeks. Conclusions: Our results suggest that bFGF-PKD-CBD/DBP may be useful for promoting fracture healing in the clinical setting.

Original languageEnglish
Article number59
JournalJournal of Orthopaedic Surgery and Research
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 12 2015

Fingerprint

Fracture Healing
Bony Callus
Kidney Diseases
Fibroblast Growth Factor 2
Powders
Polycystic Kidney Diseases
Collagen
Bone and Bones
Bone Matrix
Protein Domains
Bone Density
Microbial Collagenase
Fibroblast Growth Factor 4
Phosphates
Bone Development
Bone Fractures
Femur

Keywords

  • Allogenic demineralized bone matrix
  • Basic fibroblast growth factor
  • Bone powder
  • Collagen-binding domain
  • Fracture healing

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Acceleration of callus formation during fracture healing using basic fibroblast growth factor-kidney disease domain-collagen-binding domain fusion protein combined with allogenic demineralized bone powder. / Saito, Wataru; Uchida, Kentaro; Matsushita, Osamu; Inoue, Gen; Sekiguchi, Hiroyuki; Aikawa, Jun; Fujimaki, Hisako; Takaso, Masashi.

In: Journal of Orthopaedic Surgery and Research, Vol. 10, No. 1, 59, 12.12.2015.

Research output: Contribution to journalArticle

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abstract = "Background: To repair fractures with large bone defects or gaps, demineralized allogenic bone matrix (DBM) is often applied to the fracture site. However, studies have shown that the use of DBM alone has limited efficacy for repairing fractures. In the present study, we developed an allogenic demineralized bone powder (DBP) with basic fibroblast-derived growth factor containing a polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) from Clostridium histolyticum collagenase (ColH) and investigated the stimulatory effects of bFGF-PKD-CBD combined with allogenic DBP on bone growth in a mouse femur fracture model. Methods: DBP mixed with either phosphate-buffered saline (PBS) (DBP/PBS), 0.58 nmol basic fibroblast growth factor (bFGF) (0.58 nmol DBP/bFGF), 0.058 nmol bFGF-PKD-CBD (0.058 nmol DBP/bFGF-PKD-CBD), or 0.58 nmol bFGF-PKD-CBD (0.58 nmol DBP/bFGF-PKD-CBD) was grafted into fracture sites. Results: bFGF-PKD-CBD/DBP composite accelerates callus formation in a bone fracture model in mice and clearly showed that the composite also increases bone mineral density at fracture sites compared to bFGF/DBP. In addition, bFGF-PKD-CBD/DBP increased callus volume and bone mineral content to similar levels in fractures treated with a tenfold higher amount of bFGF at 4 weeks. Conclusions: Our results suggest that bFGF-PKD-CBD/DBP may be useful for promoting fracture healing in the clinical setting.",
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AU - Saito, Wataru

AU - Uchida, Kentaro

AU - Matsushita, Osamu

AU - Inoue, Gen

AU - Sekiguchi, Hiroyuki

AU - Aikawa, Jun

AU - Fujimaki, Hisako

AU - Takaso, Masashi

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AB - Background: To repair fractures with large bone defects or gaps, demineralized allogenic bone matrix (DBM) is often applied to the fracture site. However, studies have shown that the use of DBM alone has limited efficacy for repairing fractures. In the present study, we developed an allogenic demineralized bone powder (DBP) with basic fibroblast-derived growth factor containing a polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) from Clostridium histolyticum collagenase (ColH) and investigated the stimulatory effects of bFGF-PKD-CBD combined with allogenic DBP on bone growth in a mouse femur fracture model. Methods: DBP mixed with either phosphate-buffered saline (PBS) (DBP/PBS), 0.58 nmol basic fibroblast growth factor (bFGF) (0.58 nmol DBP/bFGF), 0.058 nmol bFGF-PKD-CBD (0.058 nmol DBP/bFGF-PKD-CBD), or 0.58 nmol bFGF-PKD-CBD (0.58 nmol DBP/bFGF-PKD-CBD) was grafted into fracture sites. Results: bFGF-PKD-CBD/DBP composite accelerates callus formation in a bone fracture model in mice and clearly showed that the composite also increases bone mineral density at fracture sites compared to bFGF/DBP. In addition, bFGF-PKD-CBD/DBP increased callus volume and bone mineral content to similar levels in fractures treated with a tenfold higher amount of bFGF at 4 weeks. Conclusions: Our results suggest that bFGF-PKD-CBD/DBP may be useful for promoting fracture healing in the clinical setting.

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KW - Collagen-binding domain

KW - Fracture healing

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