title: Novel animal model of calvarial defect: part III. Reconstruction of an irradiated wound with rhBMP-2.
abstract: BACKGROUND
  Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to be an effective therapy in the acute calvarial defect wound and in calvarial defects complicated by chronic scar. The authors compared the effectiveness of rhBMP-2 with the accepted standard of autologous graft for repair of irradiated calvarial defects.
  
  
  METHODS
  Nineteen adult New Zealand White rabbits underwent subtotal calvariectomy. Four days postoperatively, animals received 15 Gy to their wound. Six weeks postoperatively, scars were débrided and defects reconstructed in one of four groups: empty (n = 3), vehicle (buffer solution/absorbable collagen sponge; n = 3), cryopreserved autograft, (n = 3), or rhBMP-2 repair (rhBMP-2/absorbable collagen sponge, n = 10). Animals underwent computed tomography imaging at 0, 2, 4, and 6 weeks, followed by euthanization and histological analysis. Percent healing was determined and a 4 × 3 mixed model analysis of variance was performed on healing versus treatment group/postoperative time.
  
  
  RESULTS
  According to radiopacity, rhBMP-2/sponge and autografts were statistically equivalent, with 99 and 89 percent healing at 6 weeks. Empty and vehicle treatment groups, with 35 and 34 percent healing, were inferior to the rhBMP-2/sponge and autograft groups (p < 0.05). Histologically, bone in the surgical control (autograft) group was less cellular and trabecular than bone formed after rhBMP-2/sponge treatment.
  
  
  CONCLUSIONS
  rhBMP-2 therapy was as effective in reconstructing calvarial defects in the unfavorable irradiated wound as in the acute, favorable calvarial wound. Compared with cryopreserved autologous graft, rhBMP-2-regenerated bone resulted in equal defect coverage, similar thickness, and greater cellularity. Further studies are necessary to demonstrate the long-term viability and remodeling rhBMP-2/sponge-generated bone.
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: Zoe M
authors.initials: ZM
authors.lastname: MacIsaac
authors.forename: James J
authors.initials: JJ
authors.lastname: Cray
authors.forename: Darren M
authors.initials: DM
authors.lastname: Smith
authors.forename: S Alex
authors.initials: SA
authors.lastname: Rottgers
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: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D015925:Cryopreservation; D004195:Disease Models, Animal; D008297:Male; D011817:Rabbits; D011829:Radiation Dosage; D011994:Recombinant Proteins / Q000627:therapeutic use; D019651:Plastic Surgery Procedures; D012886:Skull / Q000000981:diagnostic imaging / Q000293:injuries* / Q000528:radiation effects / Q000601:surgery / Q000637:transplantation; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D014945:Wound Healing / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2