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

doi:10.1186/s13018-015-0201-0

Wataru Saito, Gen Inoue + Show 6 more

Open Access

https://doi.org/10.1186/s13018-015-0201-0

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Abstract

BackgroundTo 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.MethodsDBP 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.ResultsbFGF-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.ConclusionsOur results suggest that bFGF-PKD-CBD/DBP may be useful for promoting fracture healing in the clinical setting.

Highlights

To repair fractures with large bone defects or gaps, demineralized allogenic bone matrix (DBM) is often applied to the fracture site
Effect of basic fibroblast growth factor (bFGF)-polycystic kidney disease (PKD)-collagen-binding domain (CBD)-loaded demineralized bone powder (DBP) on callus formation Callus formation at fracture sites in mice femurs grafted with DBP in phosphate-buffered saline (PBS) (PBS/DBP) or DBP loaded with bFGF or bFGF-PKD-CBD (0.058 nmol and 0.58 nmol bFGF-PKD-CBD/DBP) was evaluated after 2, 4, and 6 weeks by micro-CT imaging (Figure 2A–F)
After 6 weeks, the callus volume and bone mineral content in fracture sites grafted with 0.58 nmol bFGF-PKD-CBD/DBP were significantly higher than those found in the other three groups of treated femurs

Summary

Introduction

To repair fractures with large bone defects or gaps, demineralized allogenic bone matrix (DBM) is often applied to the fracture site. Allogenic demineralized bone matrix (DBM) is a useful bone-filling material because it serves as biologic osteoconductive scaffold that retains the trabecular collagenous structure of the original tissue, and has bone. To overcome this limitation, strategies for the repair of large fractures with DBM should include boneinducing growth factors. In practice, bone-inducing factors rapidly diffuse in body fluid and fall below therapeutic concentrations at defect sites For this reason, large doses and/or repeated administrations of growth factors are required for sustained therapeutic effect, but such dosing regimens may be clinically impractical and expensive and can lead to adverse side effects [15,16]. To increase the osteogenic potential of bone-inducing growth factors, they should ideally be combined with a carrier, such as collagen or DBM, to promote their retention at fracture sites

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