人重组骨形态发生蛋白2及碱性成纤维细胞因子纤维蛋白复合物修复兔陈旧性关节软骨缺损：18周组织学观察

背景：纤维蛋白的天然网状结构为骨髓细胞黏附、增殖提供了良好的三维空间环境，且同时又限制了人重组骨形态发生蛋白2和碱性成纤维细胞生长因子的快速扩散，使两者随着纤维蛋白的逐渐降解而缓慢释放，最终诱导间充质细胞向软骨转化。 目的：观察人重组骨形态发生蛋白2和碱性成纤维细胞生长因子分别复合纤维蛋白后，修复兔陈旧性关节软骨缺损的效果。 设计、时间及地点：组织形态学观察，于2005-07/2006-02在石河子大学医学院完成。 材料：清洁级健康8周龄新西兰大白兔18只36膝，随机分为3组：人重组骨形态发生蛋白2组、碱性成纤维细胞生长因子组、对照组，6只12膝/组。人重组骨形态发生蛋白2，碱性成纤维细胞生长因子为英国BioSource产品；冻干人纤维蛋白原为上海莱士血制品有限公司产品。 方法：各组兔均于双侧膝关节股骨髌股关节面制备直径4 mm、深3 mm的全层软骨缺损，4周后在原切口再次开腔，清除缺损区内的纤维组织，钻通骨髓腔，成为陈旧性关节损伤。人重组骨形态发生蛋白2组用注射器注入人重组骨形态发生蛋白2+冻干人纤维蛋白原，使复合物添满缺损区；碱性成纤维细胞生长因子组同法注入碱性成纤维细胞生长因子+冻干人纤维蛋白原；对照组单纯注入等量的冻干人纤维蛋白原。 主要观察指标：光镜及电镜观察骨缺损区组织修复及软骨再生情况，并进行组织学评分。 结果：18只兔（36膝）均进入结果分析。人重组骨形态发生蛋白2组修复后10，14周，软骨缺损被白色半透明坚硬组织平滑修复，富有光泽，与正常软骨边界清楚，至18周时修复组织与正常软骨边界模糊，质地坚硬，表面平滑光润；碱性成纤维细胞生长因子组修复后10，14，18周时均有1膝关节缺损区未能完全修复；对照组全程均未见软骨修复。与对照组比较，人重组骨形态发生蛋白2组、碱性成纤维细胞生长因子组再生软骨组织学评分均明显降低（P < 0.01），且前组下降幅度优于后组（P < 0.05）。 结论：人重组骨形态发生蛋白2纤维蛋白复合物可有效修复兔陈旧性关节软骨缺损，且短期效果优于碱性成纤维细胞生长因子纤维蛋白复合物。

Effects of recombinant human bone morphogenetic protein-2 versus basic fibroblast growth factor on the repair of articular cartilage defect in rabbits: A histological observation of 18 weeks

BACKGROUND: Natural network structure of fibrinogen provides good three-dimensional environment for the adherence and proliferation of bone marrow cells, meanwhile, it restrains the diffusion of recombinant human bone morphogenetic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF). BMP-2 and bFGF will release and induce bone marrow mesenchymal cells transform into cartilages with the gradual degradation of the fibrinogen. OBJECTIVE: To observe the effect of repairing articular cartilage defects with the fibrinogen compounded with rhBMP-2 or bFGF in rabbits. DESIGN, TIME AND SETTING: The experiment, a histological observation, was performed at the Medical College of Shihezi University from September 2005 to January 2006. MATERIALS: Eighteen healthy New Zealand white rabbits (36 knees) were randomly divided into three groups: rhBMP-2 group, bFGF group and control group. rhBMP-2 and bFGF were purchased from BioSource Company (England); fibrinogen was a product of Shanghai RAAS Blood Products Co., Ltd (China). METHODS: Full-thickness defects of 4 mm in diameter and 3 mm in depth were created over the patellofemoral joint surface of both the femoral condoles by operation. After 4 weeks, the joints was opening again and the fibrous tissues in the cavity were cleaned. Medullary canal was drilled to create old injury. Fibrinogen was injected in the control group. The rhBMP-2/fibrinogen was injected into the knee cavity in rhBMP-2 group, and bFGF/fibrinogen was injected into the bFGF group. MAIN OUTCOME MEASURES: Tissue repairing and cartilage regeneration in the bone defect area were observed under light microscope and electron microscope. At the same time, the histological scores were evaluated. RESULTS: All 18 rabbits (36 knees) were involved in the final analysis. In the rhBMP-2 group, the cartilage defects were smoothly repaired by white translucent tissues, with obviously boundary to the normal joint surface after 10 and 14 weeks, and the defects boundary was hard to identify at 18weeks. In the bFGF group, the cartilage defects were smoothly repaired by white translucent tissue, but there was one knee not entirely repaired when the rabbit was been killed after 10, 14 and 18weeks. In the control group, the defect was not repaired. The rhBMP-2 group and bFGF group got a significantly reduction of histological score compared with control group (P < 0.01). The rhBMP-2 group was better than bFGF group with regard to the reducing extent (P < 0.05). CONCLUSION: The rhBMP-2/fibrinogen composites can promote the repair of old articular cartilage defects in rabbits, and it is superior to bFGF/fibrinogen in a short term.