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Novel Animal Model of Calvarial Defect: Part IV. Reconstruction of a Calvarial Wound Complicated by Durectomy

MacIsaac, Zoe M. M.D.; Levine, Benjamin A. B.A.; Smith, Darren M. M.D.; Cray, James J. Ph.D.; Shaw, Melissa B.S.; Naran, Sanjay M.D.; Kinsella, Christopher M.D.; Mooney, Mark P. Ph.D.; Cooper, Gregory M. Ph.D.; Losee, Joseph E. M.D.

Plastic and Reconstructive Surgery: April 2013 - Volume 131 - Issue 4 - p 512e–519e
doi: 10.1097/PRS.0b013e3182818b4c
Experimental: Original Articles

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 and radiation. The authors assessed the effectiveness of rhBMP-2–mediated bone regeneration in calvarial defects complicated by durectomy.

Methods: Sixteen adult New Zealand White rabbits underwent subtotal calvariectomy and dural removal, followed by dural repair and reconstruction in one of four groups: empty (n = 3), vehicle (buffer solution on an absorbable collagen sponge, n = 2), autologous graft (n = 3), or rhBMP-2 repair (rhBMP-2/absorbable collagen sponge, n = 8). Animals underwent computed tomographic imaging at 0, 2, 4, and 6 weeks postoperatively, followed by euthanasia and histologic analysis. Percent healing was determined by three-dimensional analysis. A 4 × 3 mixed model analysis of variance was performed on healing versus treatment group/postoperative time.

Results: The rhBMP-2/absorbable collagen sponge and autograft repair groups had 51.4 and 37.3 percent healing, respectively, at 6 weeks; empty and vehicle control groups had 7.8 and 17.9 percent healing, respectively, at 6 weeks. Compared with immediate favorable reconstruction (96.8 percent healing), rhBMP-2 in this setting was significantly less effective (p = 0.001). Bone in the rhBMP-2/absorbable collagen sponge group was compact and cellular but appeared only over the intact sagittal sinus and irregularly within the absorbable collagen sponge.

Conclusions: Although promising in the acute calvarial wound and other complex defects, rhBMP-2 therapy is less effective in reconstruction following dural compromise. Future studies using additional growth factors and cell therapy may improve results in this especially difficult scenario.

Pittsburgh, Pa.; and Augusta, Ga.

From the Departments of Plastic Surgery, Oral Biology, Anthropology, Orthodontics, and Bioengineering, University of Pittsburgh, and the Georgia Health Sciences University.

Received for publication July 12, 2012; accepted October 25, 2012.

Disclosure: The authors have no conflicts of interest to disclose. This study was funded by an industry grant from Medtronic, Inc., the makers of Infuse (rhBMP-2/absorbable collagen sponge) (to J.E.L.).

Joseph E. Losee, M.D.; Division of Pediatric Plastic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Children's Hospital Drive, 45th and Penn, Pittsburgh, Pa. 15201,

©2013American Society of Plastic Surgeons