牛松质骨植骨体复合骨形态发生蛋白修复贵州小型猪下颌骨缺损

Bovince cancellous bone graft and bone morphogenetic protein composite material for repairing mandibular defects of minipigs

背景:建立贵州小型猪人造下颌骨骨缺损动物模型,期望利用植骨材料的骨诱导和骨传导作用来修复缺损部位。目的:探讨骨形态发生蛋白复合牛松质骨植骨体修复下颌骨缺损的可行性。设计、时间及地点:随机对照动物实验,于2006-09/2007-07在贵阳中医学院动物研究所、遵义医学院中心实验室、四川大学组织工程实验室完成。材料:天津中津生物发展有限公司提供棒状复合骨形态发生蛋白的牛松质骨植骨体及单纯牛松质骨,规格:1.0g;0.6cm×2.5cm,其中每块植骨体骨形态发生蛋白的含量为4mg。方法:选用贵州小型猪16只,人工制造0.5cm×0.6cm×2.5cm大小的下颌骨缺损,随机分为复合材料组和单纯材料组,分别植入骨形态发生蛋白复合植骨体和单纯牛松质骨。主要观察指标:术后1周开始,用二甲酚橙、荧光素钠、四环素荧光标记物依次连续给药,通过X射线、组织学、激光共聚焦显微镜观察成骨情况。结果:①X射线片显示:10周时复合材料组植骨区和宿主骨密度基本相近,原缺损区所形成的新骨骨小梁明显,新骨改建良好;单纯材料组缺损区面积缩小,但中间仍见有周边较毛糙的透射区,宿主骨边缘所形成的新骨密度与宿主骨之间差别较大。②组织学和激光共聚焦显微镜显示:术后4周复合材料组胶原纤维丰富,成骨明显,8,10周时成骨继续增加,骨诱导明显,植骨区有大量的荧光标记物;单纯材料组4周时有少量的胶原纤维生成,10周时有少量的新骨形成,荧光标记物较弱,量少。结论:骨形态发生蛋白复合植骨体能较好地修复下颌硬骨组织缺损。

BACKGROUND： A minipig model of mandibular defect was established for repairing research using induction and conduction of bone graft materials. OBJECTIVE： To investigate the feasibility of bone morphogenetic protein and bovince cancellous bone graft composite material for repairing mandibular defects. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed in Animal Research Institute of Guiyang College of Traditional Chinese Medicine, Central Laboratory of Zunyi Medical College, and Laboratory of Tissue Engineering of Sichuan University from September 2006 to July 2007. MATERIALS： Bovince cancellous bone graft rod compositing with bone morphogenetic protein （sized 1.0 g, 0.6 cm × 2.5 cm; content of bone morphogenetic protein 4 mg） and single bovince cancellous bone graft were provided by Zimbabwe Biology Development Co., Ltd., Tianjin. METHODS： A total of 16 Guizhou miniature pigs, with artificial mandibular defect of 0.5 cm × 0.6 cm ×2.5 cm, were randomly divided into composite material group and single material group. Bovince cancellous bone graft compositing with bone morphogenetic protein and single bovince cancellous bone graft were individually implanted into the two groups. MAIN OUTCOME MEASURES： At 1 week after operation, xylenol orange, fluorescein sodium, and tetracycline fluorescent labeling drugs were given continuously, and osteogenesis was observed using X-ray examination, histological test, and confocal laser scanning microscopy. RESULTS： （1） X-ray examination demonstrated that at 10 weeks after operation, density of bone graft was similar to host bone in the composite material group, new bone trabeculae formed in original defect area was obvious, and new bone was well remodeled; in the single material group, defect area was decreased, but there was still transmission between zones, density of new bone formed by the edge of host bone was different from the host bone. （2） Histology and confocal laser scanning microscopy showed that at 4 weeks after operation, collagen fibers were rich and osteogenesis was obvious in the composite material group; at 8 and 10 weeks after operation, osteogenesis was increased, bone induction was obvious, and there were a large quantity of fluorescent markers in bone grafting area. In the single material group, at 4 weeks after operation, there was a small amount of collagen fiber formation; at 10 weeks after operation, a small quantity of new bones were formed, and the fluorescent markers were weak and less. CONCLUSION： The bovince cancellous bone graft compositing with bone morphogenetic protein can effectively repair the mandibular defect.