重组人骨形态发生蛋白2/纤维蛋白胶植入联合髓芯减压治疗兔股骨头缺血性坏死

Effect of recombinant human bone morphogenetic protein-2/fibrin sealant implantation combined with core decompression on treating avascular necrosis of the femoral head in a rabbit

背景:大量实验证明骨形态发生蛋白2不但对骨组织来源的细胞有刺激分化作用,还可诱导非骨组织来源的细胞株分化为成骨细胞。但是,许多学者在研究中发现,将骨形态发生蛋白直接用于骨的修复效果不理想。目的:将重组人骨形态发生蛋白2/纤维蛋白胶复合物植入髓芯减压后的兔激素性股骨头坏死区,观察股骨头坏死区域的新骨形成情况.设计、时间及地点:随机对照动物实验,于2005-01/2007-12在武警医学院完成。材料:在纤维蛋白胶的抑肽酶溶液内加入重组人骨形态发生蛋白2形成胶冻状的生物材料,最终聚合材料中重组人骨形态发生蛋白2的质量浓度1mg/L。方法:制造激素型股骨头缺血性坏死的动物模型,将实验动物分为3组全部进行股骨头钻孔减压,在重组人骨形态发生蛋白2/纤维蛋白组和单纯重组人骨形态发生蛋白2组孔道内植入相应材料,髄芯减压组钻孔后不植入材料。主要观察指标:MRI检查股骨头软骨及软骨下骨质信号改变,光镜下观察新骨生长情况,原子吸收分光光度仪测定钙含量。结果:MRI观察显示,植入重组人骨形态发生蛋白2/纤维蛋白胶8周后原骨缺损孔道消失,被新生骨所取代。单纯植入重组人骨形态发生蛋白2可见少量新生骨,髄芯减压组仍为纤维组织。组织形态学观察可见重组人骨形态发生蛋白2/纤维蛋白胶组术后8周原骨缺损区基本消失,有大量相对较成熟的骨小梁及板状骨并存。单纯重组人骨形态发生蛋白2组骨缺损区明显缩小,周边亦有少量骨小梁存在,新生毛细血管少见,缺损区有大量纤维组织填充。髄芯减压组术后8周缺损区缩小,周边有少量新骨形成,中心部仍为纤维组织。重组人骨形态发生蛋白2/纤维蛋白胶组钙含量显著高于另外2组(P<0.01)。结论:骨形态发生蛋白在缺血坏死的股骨头内可诱导新骨形成,与纤维蛋白胶复合后,骨形态发生蛋白诱导新骨形成的质量和数量均明显增强。

BACKGROUND： Bone morphogenetic protein-2 has been previously proved to not only stimulate and different bone tissue-derived cells, but also induce differentiation from cell strain into osteoblasts; however, direct application of bone morphogenetic protein has poor effects on repairing bone defects. OBJECTIVE： To study new bone formation in a rabbit model of avascular necrosis of the femoral head （ANFH） following recombinant human bone morphogenetic protein-2 （rhBMP-2）/fibrin sealant （FS） implantation combining with core decompression. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Affiliated Hospital of Medical College of Chinese People＇s Armed Police Force from January 2005 to December 2007. MATERIALS： Composite was made by rhBMP-2 and FS, and the final concentration of rhBMP-2 was 1 mg/L. METHODS： Animal models of ANFH were made by injecting hormone. The rabbits were randomly divided into three groups, including rhBMP-2/FS implantation group, rhBMP-2 implantation group, and core decompression alone group. MAIN OUTCOME MEASURES： Signal changes of femoral head and sclerotin were detected using MRI method; new bone formation was observed under optic microscopy; calcium content was measured using atomic absorrtion spectrophotometer. RESULTS： MRI indicated that new bone replaced primary bone defect channel at week 8 after rhBMP-2/FS implantation. A few of new bones were observed in the rhBMP-2 implantation group, and fiber tissue was still observed in the core decompression alone group. Morphology suggested that a great quantity of mature bone trabecula and plate-shaped bone replaced primary bone defect channel at week 8 after rhBMP-2/FS implantation. Bone defect was decreased in the rhBMP-2 implantation group, accompanying with a few of bone trabecula and blood capillary but a large quantity of fiber tissues. At week 8 after core decompression alone, bone defect was decreased, and a few of new bones were observed. Fiber tissue still existed in the center, and any bone tissue did not fill in it. Calcium content in the rhBMP-2/FS implantation group was greater than rhBMP-2 implantation group and core decompression alone group （P 〈 0.01）. CONCLUSION： Bone morphogenetic protein can induce new bone formation in ischemic and necrotic femoral head; in addition, the rhBMP-2/FS composite can significantly induce and improve new bone formation.