体外冲击波联合增强型纤维蛋白胶负载骨生长因子治疗兔骨不连的研究

摘要

Objective:To evaluate the effect of Extracorporeal Shock Wave combined percutaneous injection of enhanced fibrin glue loaded bone growth factor in accelerating the bone nonunion healing and promoting osteogenesis process .Methods: 48 radius model rabbits were randomly divided into four groups.Group A rabbits were treated with ESW;Group B rabbits were treated with ESW combined with FG;Group C rabbits were treated with ESW combined with FG/rhBMP-2/rhbFGF;Group D rabbits were treated with ESW combined with FG/rhBMP-2/rhbFGF/rhVEGF.After a combination therapy of 8 week,conventional X-ray radiography,optical in-spection organization form and biomechanical test were applied to evaluate the therapeutic effect .Results:Compared with the group B , the X-ray group C showed that the fracture line was fuzzy ,bony callus area began to increased ,fracture end range reduced.The histo-morphology showed that cartilage began to form , cartilage cell began to proliferate actively , and new blood vessels were forming surrounding fibrous connective tissue.Biomechanical determination found there was no statistical significance between the two groups ( P>0.05 ).FG/rhBMP-2/rhbFGF+ESW group showed the fracture line was still fuzzy , bony callus disappeared and apparent proliferative bone trabecula ,and biomechanical results showed that there was statistical significance between the two groups compared to the group B(P<0.01).FG/rhBMP-2/rhbFGF/rhVEGF+ESW group showed the fracture line was slightly fuzzy ,apparent proliferative bone trabecula in 4 week,and in 8 week,the fracture line was disappeared and moulding of healing was good.The histomorphology showed that the distribution was filled with fibrous connective tissue and many bone tissue .Biomechanical results showed that it could resistance to bending ,there was statistical significance between the two groups compared to the group C ( P<0.01 ).Conclusion: ESW therapy combined percutaneous injection of enhanced fibrin glue loaded bone growth factor can promote fracture healing and the method of combination is expected to be a good choice of non-surgical treatment of bone nonunion.%目的：欲评价体外冲击波联合增强型纤维蛋白胶负载骨生长因子经皮直接注射入骨折断端加速骨不连愈合、促进成骨过程的作用。方法：48只兔使用单纯随机抽样的方法分为4组，制备共48侧桡骨模型，并行不同方案的治疗：A组12只骨不连兔只给予ESW治疗；B组12只骨不连兔给予ESW联合纤维蛋白胶（ Fibrin Glue，FG）治疗；C组12只骨不连兔给予ESW联合 FG／骨形态发生蛋白-2（ Bone morphogenetic protein-2 rhBMP-2）／重组人碱性成纤维生长因子（ recombinant human basic fibroblast growth factor ，rhbFGF）治疗；D组12只骨不连兔给予ESW联合FG／rhBMP-2／rhbFGF／人重组血管内皮细胞生长因子（ recombinant human vsacular endothelial growth factor ，rhVEGF）治疗。联合治疗后，应用常规X线摄片、组织形态光学检查及生物力学试验等方法检测冲击波联合药物治疗后的骨折愈合情况。结果：与A组单纯体外冲击波治疗相比，B组FG＋体外冲击波治疗组骨折线稍模糊，骨痂面积开始增多，骨折断端距离缩短。组织形态学显示大片软骨形成，软骨细胞增生活跃，周围纤维结缔组织中可见新生血管形成。生物力学测定结果发现两组之间并没有差距，无统计学意义（ P＞0.05）。 C组FG／rhBMP-2／rhbFGF＋体外冲击波治疗组骨折线模糊，纤维骨痂消失，可见明显增生的骨小梁。与B组：FG＋体外冲击波治疗组相比，C组：FG／rhBMP-2／rhbFGF＋体外冲击波治疗组生物力学明显有差异，且具有显著性统计学意义（ P＜0.01）。 D组：FG／rhBMP-2／rhbFGF／rhVEGF＋体外冲击波治疗组4周时骨折线明显模糊，骨小梁明显增多。8周时骨折线消失，且愈合后塑形好。组织形态学显示以纤维结缔组织为主，中间见大量成骨细胞。与C组FG／rhBMP-2／rhbFGF＋体外冲击波治疗组相比，差异具有显著性统计学意义（P＜0.01），说明更能够提高抗弯曲力度。结论：体外冲击波联合经皮注射增强型纤维蛋白胶负载骨生长因子具有促进骨折愈合作用，有望成为一种非手术治疗骨不连的良好方法。