title: Pulsed Electromagnetic Fields Enhance Bone Morphogenetic Protein-2 Dependent-Bone Regeneration.
abstract: 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, 10 μg) of rhBMP-2 was implanted at the defect area. One week after surgery, PEMF was applied for 8 h/day over 5 days in an experimental group of animals (n = 28) using a width of 12 μs, a pulse frequency of 60 Hz, 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 5 μg rhBMP-2 (p < 0.05). In contrast, administration of 10 μg 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 10 μg 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 10 μg rhBMP-2. Therefore, our data demonstrate that PEMF can promote bone regeneration in animals treated with a low concentration of rhBMP-2.
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Dental Research Institute, Seoul National University Dental Hospital, School of Dentistry, BK 21 Plus, Seoul National University , Seoul, Korea.
authors.forename: Hoon Joo
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: 2 Department of Maxillofacial Cell and Developmental Biology, Dental Research Institute, School of Dentistry, BK 21 Plus, Seoul National University , Seoul, Korea.
authors.forename: Ri Youn
authors.initials: RY
authors.lastname: Kim
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Dental Research Institute, Seoul National University Dental Hospital, School of Dentistry, BK 21 Plus, Seoul National University , Seoul, Korea.|2 Department of Maxillofacial Cell and Developmental Biology, Dental Research Institute, School of Dentistry, BK 21 Plus, Seoul National University , Seoul, Korea.
authors.forename: Soon Jung
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001861:Bone Regeneration / Q000502:physiology*; D004574:Electromagnetic Fields; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2