title: The Efficacy of Cyclic Injection of Bone Morphogenetic Protein-2 in Large-Scale Calvarial Bone Defects.
abstract: Bone morphogenetic protein-2 (BMP-2) appears to be one of the most potent growth factors thus far studied. However, recent publications on the clinical application of BMP-2 revealed that its correct control is the paramount issue in clinical practice. For improving BMP-2 delivery, the cyclic administration might be an alternative. Accordingly, the authors cyclically injected BMP-2 in a cyclic injection model of large cranial defects to maintain the proper dosage during the bone healing process. A 10-mm diameter calvarial bone defect was produced using a round drill in 8-week-old Sprague-Dawley rats. Silk-hydroxyapatite scaffolds soaked in the appropriate concentration of BMP-2 were implanted into the defect. The animals were split into 4 single-injection groups and 3 multiple-injection groups; the latter groups received weekly subcutaneous injections of BMP-2 solution (1, 5, and 10 μg/mL) for 4 weeks, whereas the former groups received a single injection of BMP-2 at these concentrations. Each rat underwent computed tomography at 8 weeks. In terms of total volumes of the new bone, the 5 μg/mL multiple-injection BMP-2 group had significantly greater increases in bone volume than the single-injection groups. In terms of bone thickness, the multiple-injection groups had better outcomes than the single-injection groups. Thus, the cyclic injection protocol restored the original thickness without overgrowth. Cyclic injection of BMP-2 permits more accurate dosage control than single injection and improves thickness and dense bone regeneration. Therefore, it may represent a promising approach for future clinical trials. Further investigation using a greater number of animals is required.
authors.affiliation: Department of Plastic and Reconstructive Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Jin Mi
authors.initials: JM
authors.lastname: Choi
authors.forename: Woo Shik
authors.initials: WS
authors.lastname: Jeong
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Choi
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D004334:Drug Administration Schedule; D017886:Durapatite / Q000008:administration & dosage; D007267:Injections; D008297:Male; D017207:Rats, Sprague-Dawley; D047011:Silk / Q000008:administration & dosage; D012886:Skull / Q000601:surgery; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects
chemical_list: D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D047011:Silk; D017886:Durapatite