Goshima Kenichi, Nakase Junsuke, Xu Qing, Matsumoto Kunio, Tsuchiya Hiroyuki
Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
J Orthop Sci. 2012 Sep;17(5):639-48. doi: 10.1007/s00776-012-0262-4. Epub 2012 Jul 5.
Segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on bone tissue engineering. Clinical studies are ongoing to address application of hepatocyte growth factor (HGF) for treatment of some diseases; however, the use of HGF in bone tissue engineering has not been addressed. This study was performed to evaluate the effect of HGF in a complex of β-tricalcium phosphate (β-TCP) and collagen in repairing segmental bone defects.
Segmental bone defects 5 mm long were created in the middle of the tibial shafts of rabbits. The defect was stabilized with external fixators and implanted with a complex of β-TCP granules and collagen, with or without 100 μg recombinant human HGF. Biweekly, bone regeneration and β-TCP resorption were assessed radiographically and histologically. At 4 and 8 weeks, bone regeneration was evaluated by use of micro-computed tomography and mechanical tests.
Compared with the bone tissue treated with β-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of β-TCP were promoted 4 weeks postoperatively by treatment with HGF in the β-TCP and collagen group. These changes were associated with promoting biomechanical regeneration. By 8 weeks, the formation of bone marrow in newly generated bone and absorption of the β-TCP granules were completed in a shorter period by combining HGF with β-TCP and collagen, compared with tissues without HGF.
The combined application of HGF in a β-TCP and collagen matrix promoted histological bone healing and augmented mechanical strength of the healing bone, particularly in the early stages. The combined use of HGF and β-TCP for treatment of bone defects made a substantial difference.
节段性骨缺损修复仍然是一项临床和科学挑战，人们越来越关注骨组织工程。目前正在进行临床研究以探讨肝细胞生长因子（HGF）在某些疾病治疗中的应用；然而，HGF在骨组织工程中的应用尚未得到研究。本研究旨在评估HGF在β-磷酸三钙（β-TCP）和胶原蛋白复合物中修复节段性骨缺损的效果。
在兔胫骨干中部制造5毫米长的节段性骨缺损。用外固定器固定缺损，并植入β-TCP颗粒和胶原蛋白复合物，其中有的添加100μg重组人HGF，有的不添加。每两周通过影像学和组织学评估骨再生和β-TCP吸收情况。在4周和8周时，通过微计算机断层扫描和力学测试评估骨再生情况。
与用β-TCP和胶原蛋白治疗的骨组织相比，β-TCP和胶原蛋白组中添加HGF治疗术后4周促进了矿化、血管生成、新骨形成以及β-TCP的吸收。这些变化与促进生物力学再生相关。到8周时，与未添加HGF的组织相比，将HGF与β-TCP和胶原蛋白联合使用可在更短时间内完成新生骨中骨髓的形成和β-TCP颗粒的吸收。
HGF与β-TCP和胶原蛋白基质联合应用可促进组织学骨愈合并增强愈合骨的机械强度，尤其是在早期阶段。HGF与β-TCP联合用于治疗骨缺损有显著差异。
