Effect of Electroporation-Mediated Transfecting Recombinant Plasmid pIRES-hBMP2-hVEGF165 on Mandibular Distraction Osteogenesis

Distraction osteogenesis requires a long consolidation period and has a low but real failure rate. Bone morphogenetic proteins (BMPs) accelerate bone deposition in fractures and critical-sized bone defects. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing angiogenesis, and is an essential coordinator of extracellular matrix remodeling, angiogenesis, and bone formation in the growth plate. However, their effects on mandibular distraction osteogenesis are unknown. We investigated the effect of local delivery of plasmid pIRES-hBMP-2-hVEGF165 into a distraction area by electroporation-mediated approach. A New Zealand rabbit model were used. Activation of the device was commenced after 3 days of latency period and proceeded at the rate of 0.8 mm per day for 7 days. After the completion of activation, the rabbits were randomly divided into 5 groups: group A: recombinant plasmid 2 mu g (0.1 mu g/mu L) pIRES-hVEGF165-hBMP2 was injected into the distraction area after the completion of activation; group B: recombinant plasmid pIRES-hBMP2 was injected into the distraction area; group C: recombinant plasmid pIRES-hVEGF165 was injected into the distraction area; group D: pIRES was injected into the distraction area, and group E: normal saline was injected into the distraction area. After injection every group used electroporation. Subsequently, the rabbits were examined by quantitative computed tomography, mechanical testing, and histomorphometric analysis. BMD of newly formed bone of the distraction area in groups A, B, and C were remarkably higher than those of groups D and E at different times (P < 0.001). At 4 and 8 weeks of consolidation, the crushing strength of 3 points of the newly formed bone in group A was remarkably higher than those of groups B, C, D, and E (P < 0.01). The results demonstrated statistically remarkable increase in regenerated bone in the gene-transfected groups. Electroporation-mediated transfecting recombinant plasmid pIRES-hVEGF165-hBMP2 could produce a satisfactory proceeding of osteogenesis and calcification, which surpassed that of the control group. This finding indicates that a combination of VEGF and BMP may make osteogenesis and angiogenesis appear at the same time. Furthermore, it may magnify the effect of single growth factor, and promote growth and reparative process of bone.