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Novel Animal Model of Calvarial Defect: Part III. Reconstruction of an Irradiated Wound with rhBMP-2

Kinsella, Christopher R. Jr. M.D.; MacIsaac, Zoe M. M.D.; Cray, James J. Ph.D.; Smith, Darren M. M.D.; Rottgers, S. Alex M.D.; Mooney, Mark P. Ph.D.; Cooper, Gregory M. Ph.D.; Losee, Joseph E. M.D.

Plastic and Reconstructive Surgery: November 2012 - Volume 130 - Issue 5 - p 643e–650e
doi: 10.1097/PRS.0b013e318267d412
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. 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.

Pittsburgh, Pa.

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

Received for publication March 19, 2012; accepted May 25, 2012.

Presented at the 58th Annual Meeting of the Robert H. Ivy Society of Plastic Surgeons, in Philadelphia, Pennsylvania, March 9 through 10, 2012, and at the 91st Annual Meeting of the American Association of Plastic Surgeons, in San Francisco, California, April 14 through 17, 2012.

Disclosure: This study was funded by an industry grant (to Dr. Losee) from Medtronic Inc. (Minneapolis, Minn.), the makers of Infuse (rhBMP-2/ACS). The authors have no other financial interest to declare.

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

©2012American Society of Plastic Surgeons