Bone regeneration in rats with BMP-4 and VEGF plasmid DNA

Abstract

Problem: Gene therapy offers a promising new method of bone regeneration. One technique uses bioresorbable polymer scaffolding at the bony defect site that contains plasmid DNA of bone growth factors. Previous studies have demonstrated bone growth using bone morphogenetic protein-4 (BMP-4) plasmid DNA. Research has suggested a synergistic effect of BMP-4 and vascular endothelial growth factor (VEGF) on bone regeneration. The present study aims to confirm bone regeneration with a polymer scaffold containing BMP-4 plasmid DNA in the rat calvarial defect model and to quantify a synergistic effect of BMP-4 and VEGF plasmid DNA in this model. Methods: Calvarial critical-sized defects were created in 100 male Sprague-Dawley rats. The animals were divided into 5 equal groups by treatment: none (negative control); VEGF plasmid DNA; BMP-4 plasmid DNA; VEGF and BMP-4 plasmid DNA; and autograft (positive control). The animals were euthanized at 4 and 8 weeks; calvaria were radiographed and histologically sectioned. Results: Radiomorphometry measured bone growth within the calvarial defects to quantify the bone regeneration effects of BMP-4 and VEGF plasmid DNA alone and in combination. Compared to control groups, significant bone growth was noted in the BMP-4 and BMP-4/VEGF groups, but no bone growth was noted in the VEGF group. No significant difference in bone growth was noted between the BMP-4 and BMP-4/VEGF groups. Microscopy of histologic sections (1 slide/specimen) confirmed the bone growth noted on radiomorphometry. Conclusion: BMP-4 plasmid DNA demonstrates significant bone growth in the rat calvarial defect model. VEGF plasmid DNA alone demonstrates no bone growth. When BMP-4 and VEGF plasmid DNA are combined, no synergistic effect is noted. Significance: Reconstruction of osseous craniofacial defects such as autografting for cleft palate and osteocutaneous free tissue transfer for mandibular defects often requires bone harvest with an associated donor site morbidity. Tissue engineering employing gene therapy for bone regeneration may offer a less morbid alternative. Support: None reported.