Comparison of BMP‐2 and ‐4 for rat mandibular bone regeneration at various doses1

Abstract

To compare mandibular bone regeneration with bone morphogenetic proteins-2 and -4 (BMP-2 and -4) at varying doses. Defects were created in the left hemi-mandibles of 82 Sprague-Dawley rats. The defects were filled with a hyaluronic acid polymer loaded with 0.01, 0.1, 1, or 10 microg of BMP-2 or -4. Control groups consisted of animals with unfilled defects, or with defects filled with the hyaluronic acid sponges loaded with growth factor dilution buffer. Animals were killed after 8 weeks, and the hemi-mandibles were analyzed histologically using stereologic techniques. Mandibles implanted with carriers containing 10 microg of BMP-2 or -4 differed significantly from controls in terms of new bone area (p = 0.01 and p = 0.0001, respectively). Marrow space development occurred in a dose-dependent fashion (p < 0.0001 for both growth factors), and this effect was more pronounced for BMP-2 at larger doses (p < 0.0001 at 1 and 10 microg doses). New bone areas and volumes did not differ significantly between the growth factors. While defects implanted with BMP-4 tended to have thicker cortical bone and more trabecular bone, at least partial defect bridging was achieved in a greater number of defects implanted with BMP-2 (47%) than with BMP-4 (35%). Although similar areas and volumes of new bone were induced with BMP-2 and -4, differences were noted in the quality of bone generated with each growth factor. The results indicate a threshold dose for acute administration between 1 and 10 mug BMP-2 for bony union in this model, and > or =10 microg for BMP-4. These findings suggest that differences in bone growth factor osteogenic potential deserve further study and may have an impact on the translation of osteoinductive protein therapy into clinical practice.