hBMP-2基因修饰的组织工程化骨修复兔下颌骨正中缝的实验研究

Repair of mandibular central fissures in rabbits with hBMP-2 gene modified tissue engineered bone

目的:评价腺病毒介导的人骨形成蛋白-2(Ad-hBMP-2)基因转染的组织工程化人工骨对兔下颌骨正中缝的修复效果。方法:健康成年新西兰大白兔45只,随机分为5组,去除下颌骨正中缝的软组织,分别植入如下人工骨:Ⅰ组,Ad-hBMP-2转染的成骨细胞复合倍骼生(Bioglass)(10只);Ⅱ组,腺病毒介导的增强型绿色荧光蛋白(Ad-EGFP)基因转染的成骨细胞复合倍骼生(10只);Ⅲ组,未转染的成骨细胞复合倍骼生(10只);Ⅳ组,单纯倍骼生(10只);Ⅴ组,空白对照(5只)。于术后第2、4、8、12周末行大体观察、X线检查、组织学检查、新生骨量分析和生物力学测定。应用单因素方差分析和多样本均数两两比较的q(Newman-Keuls)检验对实验结果进行统计学分析。结果:大体观察见,4周时,Ⅰ组的兔下颌骨正中缝被新生骨组织代替,表面有皮质骨生成。X线检查,第4、8周,Ⅰ组的下颌骨正中缝内有明显骨痂形成。新生骨量分析显示,与其他组相比,Ⅰ组的新生骨量最多(P<0.01)。Ⅰ组移植骨的最大抗弯曲负荷、弯曲刚度值显著大于其他各组(P<0.01)。结论:hBMP-2基因修饰的组织工程化人工骨可以较好地修复兔下颌骨正中缝,有可能用于牙槽突裂的骨性修复。

PURPOSE： To evaluate the effectiveness of the tissue engineered bone substitute loaded with periostealderived osteoblasts （POBs） transfected by adenovirus mediated human bone morphogenetic protein-2 gene （Ad-hBMP-2） in the repair of rabbit mandibular central fissures. METHODS： 45 rabbits with the soft tissue in the mandibular central fissures removed were randomly divided into 5 groups,group I：Ad-hBMP-2 transfected POBsPoioglass group （n=10）;group Ⅱ：adenovirus mediated enhanced green fluorescent protein （Ad-EGFP） gene transfected POBsPoioglass group （n=10）;group Ⅲ：untransfected POBs/bioglass group （n=10）;group Ⅳ：single bioglass group （n=10）;group Ⅴ：control group （n=5）.The above bone substitutes were implanted in the rabbit mandibular central fissures respectively except group Ⅴ.The samples were studied by gross,X-ray, histomorphology,histomorphometrical analysis and biomechanics after 2,4,8,12 weeks respectively. One-way ANOVA was used for statistical analysis. RESULTS： In gross view, the rabbit mandibular central fissures in group Ⅰ were replaced by new bone including cortical bone from the 4th week.X-ray examination showed that the higher bone density was found in the rabbit mandibular central fissures of group Ⅰ 4 to 8 weeks after implantation. Histomorphometrical analysis showed much more new bony callus in group Ⅰ than in other groups （P〈0.01）. The maximal anti-bending load and bending rigidity of the implanted bone substitute of group Ⅰ were significantly higher than those of group Ⅱ,Ⅲ and Ⅳ（P〈0.01）.CONCLUSION：The tissue engineered bone substitute loaded with POBs transfected by human BMP-2 gene could get the best result in the repair of rabbit mandibular cemtral fissures,therefore,it is likely to be used in the repair of alveolar clefis.Supported by National Natural Science Foundation of China（30271349）.