title: BMP-2-mediated regeneration of large-scale cranial defects in the canine: an examination of different carriers.
abstract: BACKGROUND
  Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge is a U.S. Food and Drug Administration-approved therapy shown to be an effective means of generating bone formation in multiple clinical settings. However, the optimum dose and delivery of rhBMP-2 to the calvaria are undetermined. The aim of the authors' study was to investigate the use of rhBMP-2 in addressing calvarial defects in a large-animal model through a variety of modifications to this U.S. Food and Drug Administration-approved therapy.
  
  
  METHODS
  Twenty-three adult canines underwent the creation of a standard calvarial defect and received either no treatment, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with corticocancellous chips, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules, or 0.4 mg/ml rhBMP-2 in a compression-resistant matrix carrier. Direct comparisons of defect radiopacity were performed at 0, 8, 16, and 24 weeks postoperatively before the animals were euthanized. All specimens were evaluated qualitatively with histology.
  
  
  RESULTS
  Surgical control animals had an average defect radiopacity of 32.7 percent at study completion compared with an average of 99.95 percent across all treatment groups. Ectopic bone formation was found consistently in all treatment groups with varying degrees of severity. Regenerated bone thickness, compactness, and organization varied qualitatively between groups.
  
  
  CONCLUSIONS
  Treatment with 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules showed the least amount of ectopic bone formation and the most compact bone formation within the defect, and produced reasonably consistent bony thickness across the defect. Future studies should focus on spatial regulation of rhBMP-2 to minimize unwanted bone formation.
authors.affiliation: Pittsburgh, Pa. From the Division of Plastic Surgery and the Departments of Oral Biology, Anthropology, Orthodontics, and Bioengineering, University of Pittsburgh.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Kinsella
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bykowski
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Lin
authors.forename: James J
authors.initials: JJ
authors.lastname: Cray
authors.forename: Emily L
authors.initials: EL
authors.lastname: Durham
authors.forename: Darren M
authors.initials: DM
authors.lastname: Smith
authors.forename: Gary E
authors.initials: GE
authors.lastname: DeCesare
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
mesh_terms: D000287:Administration, Topical; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis*; D001861:Bone Regeneration / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012887:Skull Fractures / Q000503:physiopathology*; D015503:Surgical Sponges; D016896:Treatment Outcome
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins