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Porcine Allograft Mandible Revitalization Using Autologous Adipose-Derived Stem Cells, Bone Morphogenetic Protein-2, and Periosteum

Runyan, Christopher M. M.D., Ph.D.; Jones, Donna C. Ph.D.; Bove, Kevin E. M.D.; Maercks, Rian A. M.D.; Simpson, David S. B.S.; Taylor, Jesse A. M.D.

Plastic and Reconstructive Surgery: May 2010 - Volume 125 - Issue 5 - p 1372-1382
doi: 10.1097/PRS.0b013e3181d7032f
Experimental: Original Articles

Background: Critical defects of the craniomaxillofacial region are often treated with vascularized osteocutaneous free flaps. These lengthy operations may be associated with considerable donor-site morbidity and suboptimal functional and aesthetic results. To overcome these issues, this study investigates an engineered vascularized bone flap using allograft bone, adipose-derived stem cells, and recombinant human bone morphogenic protein (rhBMP)-2 and compares two alternative blood supplies.

Methods: Edentulous porcine hemimandibles were commercially sterilized, packed with rhBMP-2-soaked absorbable collagen sponge and autologous, culture-expanded adipose-derived stem cells, and implanted into two locations within 10 pigs: (1) an intercostal-based periosteal envelope (thoracic) and (2) within the rectus abdominis muscle with insertion of the superficial inferior epigastric vascular pedicle into the medullary cavity (abdominal). The constructs were incubated in vivo for 7 to 8 weeks and harvested to assess de novo bone formation.

Results: Radiographic, micro–computed tomographic, and histologic assessments of harvested constructs were performed. Abdominal constructs had a thin rim of new, cancellous bone surrounding a fibrotic core with little allograft remaining. Thoracic allografts were absorbed completely and replaced with new, full-thickness, cancellous bone. Calcitic tissue content was significantly higher in thoracic (474.16 ± 75.93 ml) compared with abdominal (143.20 ± 46.39 ml) constructs (p < 0.006). New bone in both groups contained Haversian systems, but only thoracic constructs contained marrow elements and blood vessels resembling normal bone.

Conclusions: These data demonstrate revitalization of large-volume allograft bone, and have positive implications for bone tissue engineering. Allograft revitalization in thoracic but not abdominal constructs reinforces the critical role of the periosteum in the process.


Cincinnati, Ohio

From the Department of Surgery, Division of Plastic Surgery, and the Department of Pediatrics, Division of Pathology, Cincinnati Children's Hospital Medical Center.

Received for publication August 7, 2009; accepted November 24, 2009.

Presented at the 88th Annual Meeting of the American Association of Plastic Surgeons, in Rancho Mirage, California, March 21 through 25, 2009; the Ohio Valley Plastic Surgery Society Annual Conference, in Indianapolis, Indiana, May 17 through 19, 2009; and the 54th Annual Meeting of the Plastic Surgery Research Council, in Pittsburgh, Pennsylvania, May 27 through 30, 2009.

Disclosures: This work was supported by funds from the Division of Plastic Surgery, at the Cincinnati Children's Hospital Medical Center. Medtronic donated recombinant human bone morphogenetic protein-2 protein and collagen sponge used in the experiment. The processing of allograft bone was performed, as a free service, by RTI Biologics. None of the authors has a financial interest either in Medtronic or in RTI Biologics.

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Jesse A. Taylor, M.D. Division of Plastic Surgery; Cincinnati Children's Hospital Medical Center; 3333 Burnet Avenue, ML 2020; Cincinnati, Ohio 45229;

©2010American Society of Plastic Surgeons