Pulsed Electromagnetic Fields Enhance Bone Morphogenetic Protein-2 Dependent-Bone Regeneration

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the purpose of promoting bone regeneration is emerging; however, the high dose of rhBMP-2 required in humans is accompanied by several limitations, including bone resorption and swelling. To reduce the dose of rhBMP-2 required, the applicability of pulsed electromagnetic fields (PEMF) was evaluated using a rat calvarial defect model. After creating an 8-mm-diameter calvarial bone defect, a collagen sponge soaked in different concentrations (0, 2.5, 5, 10g) of rhBMP-2 was implanted at the defect area. One week after surgery, PEMF was applied for 8h/day over 5 days in an experimental group of animals (n = 28) using a width of 12s, a pulse frequency of 60Hz, and a magnetic intensity of 10 G. Animals were sacrificed 4 weeks after surgery and assessed by microcomputed tomography and histological and immunohistochemical analyses. In the absence of application of PEMF, bone volume, bone mineral density, trabecular thickness, trabecular number, and trabecular separation, all showed statistically significant differences, depending on the concentration of rhBMP-2 utilized (p < 0.001). PEMF accelerated bone regeneration in the groups that received 0, 2.5, and 5g rhBMP-2 (p < 0.05). In contrast, administration of 10g rhBMP-2 resulted in no additive effect on bone regeneration in combination with PEMF. Groups receiving no rhBMP-2 showed distinct bone regeneration in the central zone of the bone defect when treated with PEMF, whereas they failed to bridge the defect space without PEMF. Among the groups without PEMF, soft tissue infiltrations from the outer surface on the skin side were common. Among groups with PEMF, the groups receiving 5 and 10g rhBMP-2 displayed denser bone with significantly reduced dead spaces. The application of PEMF did not result in an accelerated effect on bone regeneration in groups treated with 10g rhBMP-2. Therefore, our data demonstrate that PEMF can promote bone regeneration in animals treated with a low concentration of rhBMP-2.