Awa. Baltzer et al., Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene, GENE THER, 7(9), 2000, pp. 734-739
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.