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.
Portland, Ore.; and Simi Valley, Calif. From the Department of Surgery, Division of Plastic and Reconstructive Surgery, School of Medicine, and the Department of Restorative Dentistry, Division of Biomaterials and Biomechanics, School of Dentistry, Oregon Health and Science University, and the Westlake Surgical Center.
Joyce C
JC
Chen
Shelley R
SR
Winn
Xi
X
Gong
Wayne H
WH
Ozaki
D000367:Age Factors; D000539:Alveolar Process / Q000601:surgery*; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D004285:Dogs; D015316:Genetic Therapy; D008437:Maxilla / Q000601:surgery*; D011994:Recombinant Proteins / Q000627:therapeutic use*
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins