Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene

This study evaluated the ability of gene transfer to enhance bone healing. Segmental defects were created surgically in the femora of New Zealand whit e rabbits. First generation adenoviruses were used as vectors to introduce into the defects genes encoding either human bone morphogenetic protein-2 ( BMP-2) or, as a negative control, firefly luciferase. Representative specim ens were evaluated histologically after 8 weeks. Healing of the defects was monitored radiographically for 12 weeks, after which time the repair tissu e was evaluated biomechanically. By radiological criteria, animals receivin g the BMP-2 gene had healed their osseous lesions after 7 weeks, whereas th ose receiving the luciferase gene had not. Histologic examination of repres entative rabbits at 8 weeks confirmed ossification across the entire defect in response to the BMP-2 gene, whereas the control defect was predominantl y fibrotic and sparsely ossified. At the end of the 12-week experiment, the control femora still showed no radiological signs of stable healing. The d ifference in radiologically defined healing between the experimental and co ntrol groups was statistically significant (P < 0.002). Biomechanical testi ng of the femora at 12 weeks demonstrated statistically significant increas es in the mean bending strength (P < 0.005) and bending stiffness (P < 0.05 ) of the animals treated with the BMP-2 gene. Direct, local adenoviral deli very of an osteogenic gene thus led to the healing of an osseous lesion tha t otherwise would not do so. These promising data encourage the further dev elopment of genetic approaches to enhancing bone healing.