骨形态发生蛋白-2基因修饰的组织工程化骨修复羊胫骨干骨缺损

目的 评价腺病毒介导的人骨形态发生蛋白2(Adv-hBMP-2)基因转染的组织工程化人工骨对大动物长骨干骨缺损的修复效果。方法 建立羊胫骨干骨缺损模型(2．6cm),单侧(右)植人体外构建的组织工程化骨,26只羊分为5组：(1)Adv-hBMP-2转染的骨髓间充质干细胞(BMSC)加煅烧骨(CB)组(9侧);(2)腺病毒介导的β-半乳糖苷酶(Adv-βgal)基因转染的BMSC加CB组(6侧);(3)未转染的BMSC加CB组(6侧);(4)单纯CB组(3侧);(5)未治疗组(2侧)。分期行X线、计量组织学检查和生物力学测定。结果 X线：4～8周,Adv-hBMP-2转染组的羊胫骨干骨缺损内有明显骨痂形成;26周,(1)、(2)、(3)、(4)和(5)组的完全愈合率,分别为5／8、1／5、0／5、0／2、0／1。计量组织学示,与其他组相比,1组的新生骨量最多,并有皮质骨形成;第1组移植骨的压缩载荷和弹性模量明显大于其他各组。结论 hBMP-2基因修饰的组织工程化人工骨可以修复大动物(羊)负重骨(胫骨)的节段性缺损。

BMP-2 gene modified tissue-engineered bone repairing segmental tibial bone defects in goats

OBJECTIVE: To evaluate the effectiveness of the tissue-engineered bone substitute loaded with adenovirus mediated human bone morphogenetic protein-2 gene (Adv-hBMP-2) transfected bone marrow derived mesenchymal stem cells (BMSC) in the repair of diaphyseal segmental bone defect of large animal. METHODS: The right tibial bone defects (2.6 cm) model of 26 goats were established and divided into 5 groups: I. Adv-hBMP-2 transfected BMSC/calcined bone (CB) group (n = 9); II. adenovirus-beta-galactosidase (Adv-betagal) gene transfected BMSC/CB group (n = 6); III. untransfected BMSC/CB group (n = 6); IV. single CB group (n = 3); VI. untreated group (n = 2). The above tissue-engineered bone substitutes were implanted in the bone defects respectively except group VI. Roentgenography, histomorphometrical analysis and biomechanical measurement were studied at various times. RESULTS: X-ray: at 4 - 8th weeks after implantation, more bony callus was found in the bone defects of group I. The complete healing rates of group I, II, III, IV, and V were 5/8, 1/5, 0/5, 0/2, 0/1 respectively at 26th week after implantation. Histomorphometrical analysis showed much more new bony callus including cortical bone formed in group I than those of other groups. The compression strength of the implanted bone substitute of group I is significantly higher than those of group II and III. CONCLUSION: The tissue-engineered bone substitute loaded with human BMP-2 gene transfected BMSC can repair diaphyseal segmental bone defect of large animal (goat).