An insufficient fracture healing process causes bone nonunion at fracture sites, resulting in dysfunction. In racehorses, fractures can cause large economic losses because repair requires long-term rest; thus, affected horses are prevented from entering races. Fractures in horses are currently treated with external fixation by means of a cast or with internal fixation by use of metal plates and screws. These treatment strategies basically depend on the biogenic healing ability of bone. Bone regeneration methods that make use of various biogenic cytokines combined with surgical procedures have been proposed to enhance the process of fracture healing.1 Growth factors that enhance bone metabolism include acidic fibroblast growth factor,2–4 bFGF,5 bone morphogenic proteins,6–8 transforming growth factor-β1,4,9,10 insulin-like growth factor-1,1,11 and platelet-derived growth factor-BB.12,13 Among these factors, bFGF is recognized as a potent mitogen for various mesenchymal cells14,15 and reportedly induces vascularization11,16 and bone regeneration.17–19 This growth factor is also believed to regulate bone formation because of its ability to stimulate osteoblast cells to differentiate and proliferate.19 Therefore, treatment of horses with bFGF should theoretically shorten the rest period needed for fracture healing.
Generally, it is difficult for a saline (0.9% NaCl) solution containing a cell growth factor to exert the desired effect via injection into the target site because cell growth factors, including bFGF, are unstable and have a short intravital half-life. In fact, in a study20 in which rats were treated with bFGF, a solution of bFGF mixed with fibrin gel rapidly diffused away from the injection site and was metabolized. It has been suggested that drug delivery systems can be used to accurately deliver agents that have short intravital half-lives. With bFGF injection, a prolonged intravital effect can be achieved via sustained release of the growth factor. Various biodegradable polymers that act as carriers when combined with bFGF reportedly provide that sustained release.21–23 Cell growth factors combined with biodegradable carriers, such as collagen or gelatin, are continuously released by gradual hydrolysis of carriers, resulting in prolonged effects at the injection site.
Among available carriers, biodegradable hydrogel microspheres purified from gelatin have attracted great interest. Gelatin hydrogel microspheres do not degrade by simple hydrolysis but rather by proteolysis.23 Furthermore, speed of degradation of these microspheres is affected by their water content and can, therefore, be controlled.23 Use of gelatin hydrogel microspheres containing bFGF to treat bone fractures leads to vascularization24 and bone regeneration.19,25 The purpose of the study reported here was to evaluate the effect of intra-articular injection of gelatin hydrogel microspheres containing bFGF on experimentally induced defects in MC3s of horses, in vivo.
Basic fibroblast growth factor
Third metacarpal bone
Multidetector-row computed tomography
Isoelectric point, version 5.0, Nitta Gelatin Co, Kyoto, Japan.
Ultrafree-0.5, Millpore, Kyoto, Japan.
Trafermin Fiblast Spray 250, Kaken Pharmaceutical Co Ltd, Tokyo, Japan.
Domitor (0.1%), Nippon Zenyaku Kougyou Co Ltd, Osaka, Japan.
Horizon (0.5%), Astellas Inc, Tokyo, Japan.
Veterinary Ketalar 50, Sankyo Yell Yakuhin Co Ltd, Tokyo, Japan.
ALPS Pharmaceutical Industries Co Ltd, Tokyo, Japan.
Furosen, Takeda Pharmaceutical Industry Co Ltd, Tokyo, Japan.
Retamex (2%), Sankyo Yell Yakuhin Co Ltd, Tokyo, Japan.
Coaxin, Tobishi Pharmaceutical Co Ltd, Tokyo, Japan.
Banamine (5%), Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan.
2-0 Vicryl, Johnson & Johnson, Tokyo, Japan.
2-0 Ethilon, Johnson & Johnson, Tokyo, Japan.
Melolin, Smith & Nephew, Tokyo, Japan.
Coban, 3M, Tokyo, Japan.
Blesin tablet, Sawai Pharmaceutical Co Ltd, Tokyo, Japan.
XG-1V, Fuji Film Co, Tokyo, Japan.
Asterion 4, Toshiba, Tokyo, Japan.
Virtual Place Advance, AZE, Tokyo, Japan.
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