Saito Hiroki, Shoji Shintaro, Kuroda Akiyoshi, Inoue Gen, Tazawa Ryo, Sekiguchi Hiroyuki, Fukushima Kensuke, Miyagi Masayuki, Takaso Masashi, Uchida Kentaro
Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Japan.
Shonan University of Medical Sciences Research Institute, Chigasaki City, Japan.
Biomed Mater Eng. 2023;34(6):537-544. doi: 10.3233/BME-230021.
A combination of synthetic porous materials and BMP-2 has been used to promote fracture healing. For bone healing to be successful, it is important to use growth factor delivery systems that enable continuous release of BMP-2 at the fracture site. We previously reported that in situ-formed gels (IFGs) consisting of hyaluronan (HyA)-tyramine (TA), horseradish peroxidase and hydrogen peroxide enhance the bone formation ability of hydroxyapatite (Hap)/BMP-2 composites in a posterior lumbar fusion model.
We examined the effectiveness of IFGs-HyA/Hap/BMP-2 composites for facilitating osteogenesis in refractory fracture model mice.
After establishing the refractory fracture model, animals were either treated at the site of fracture with Hap harboring BMP-2 (Hap/BMP-2) or IFGs-HyA with Hap harboring BMP-2 (IFGs-HyA/Hap/BMP-2) (n = 10 each). Animals that underwent the fracture surgery but did not receive any treatment were considered the control group (n = 10). We determined the extent of bone formation at the fracture site according to findings on micro-computed tomography and histological studies four weeks following treatment.
Animals treated with IFGs-HyA/Hap/BMP-2 demonstrated significantly greater bone volume, bone mineral content and bone union than those treated with vehicle or IFG-HyA/Hap alone.
IFGs-HyA/Hap/BMP-2 could be an effective treatment option for refractory fractures.
合成多孔材料与骨形态发生蛋白-2（BMP-2）联合使用已被用于促进骨折愈合。为使骨愈合成功，使用能够在骨折部位持续释放BMP-2的生长因子递送系统很重要。我们之前报道过，由透明质酸（HyA）-酪胺（TA）、辣根过氧化物酶和过氧化氢组成的原位形成凝胶（IFG）在腰椎后路融合模型中增强了羟基磷灰石（Hap）/BMP-2复合材料的骨形成能力。
我们研究了IFG-HyA/Hap/BMP-2复合材料在难治性骨折模型小鼠中促进成骨的有效性。
建立难治性骨折模型后，动物在骨折部位分别接受含BMP-2的Hap（Hap/BMP-2）或含BMP-2的Hap与IFG-HyA（IFG-HyA/Hap/BMP-2）治疗（每组n = 10）。接受骨折手术但未接受任何治疗的动物作为对照组（n = 10）。治疗四周后，根据微型计算机断层扫描和组织学研究结果确定骨折部位的骨形成程度。
与接受载体或单独的IFG-HyA/Hap治疗的动物相比，接受IFG-HyA/Hap/BMP-2治疗的动物表现出明显更大的骨体积、骨矿物质含量和骨愈合。
IFG-HyA/Hap/BMP-2可能是难治性骨折的一种有效治疗选择。
