rhBMP-4 gene therapy in a juvenile canine alveolar defect model.

BACKGROUND

Autologous bone grafts have the disadvantages of donor-site pain and morbidity, finite supply, increased costs, and prolonged hospitalizations. Using a juvenile canine model, the authors hypothesized that recombinant human (rh) bone morphogenetic protein (BMP)-4 gene therapy-treated alveolar defects would promote bone healing and canine tooth eruption equal to their autografted counterparts.

METHODS

Sixty-five maxillary alveolar defects were created in juvenile foxhound dogs with a mean age of 80.8 days. Nineteen defects were treated with DNA plasmid encoding rhBMP-4, 16 defects were autografted, 15 defects contained scaffold only, and 15 defects were left unrepaired. At 4 and 12 weeks after surgery, bone density and tooth eruption were measured, respectively. Data were subjected to one-way analysis of variance testing with statistical significance established at p < 0.05.

RESULTS

At 4 weeks, the bone densities in the rhBMP-4, autografted, scaffold-only, and defect-only groups were 31.2 +/- 6.5, 30.5 +/- 8.1, 18.4 +/- 3.8, and 15.2 +/- 4.0 percent, respectively. A significant effect (p < 0.05) was observed between the rhBMP-4 gene therapy-treated and autografted groups compared with the scaffold-only and defect-only groups. At 12 weeks, the rates of tooth eruption measured in the rhBMP-4, autografted, scaffold-only, and defect-only groups were 67.4 +/- 15.8, 58.3 +/- 18.8, 52.7 +/- 16.2, and 45.0 +/- 13.3 percent, respectively. A significant effect (p < 0.05) was observed between the rhBMP-4 gene therapy-treated and defect-only groups.

CONCLUSIONS

In the present studies, rhBMP-4 gene therapy was equivalent to autografting and superior to the scaffold-only and unrepaired defect in bone regeneration and tooth eruption. With decreased morbidity and cost, rhBMP-4 gene therapy may ultimately become an alternative to autografting to repair bony defects.