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Regenerative Surgery in Cranioplasty Revisited: The Role of Adipose-Derived Stem Cells and BMP-2

Smith, Darren M. M.D.; Cooper, Gregory M. Ph.D.; Afifi, Ahmed M. M.D.; Mooney, Mark P. Ph.D.; Cray, James Ph.D.; Rubin, J. Peter M.D.; Marra, Kacey G. Ph.D.; Losee, Joseph E. M.D.

Plastic and Reconstructive Surgery: November 2011 - Volume 128 - Issue 5 - p 1053–1060
doi: 10.1097/PRS.0b013e31822b65e4
Experimental: Original Articles

Background: Reconstruction of the pediatric calvaria is frequently complicated by a shortage of bone. This problem is most apparent between 2 and 10 years of age, when the osteogenic potential of the dura is diminished and the diploic space has not matured to the point that split-thickness calvarial grafting is practical. In this article, the authors evaluate and compare the relative efficacy of adipose-derived stem cells, bone morphogenetic protein (BMP)-2, and adipose-derived stem cells osteoinduced with BMP-2 in addressing these defects.

Methods: Cranial defects measuring 15 × 15 mm were created in New Zealand White rabbits. Five treatment modalities were compared: no repair (surgical control); untreated acellular collagen sponge (vehicle control); BMP-2 on acellular collagen sponge; adipose-derived stem cells on acellular collagen sponge; and osteoinduced adipose-derived stem cells on acellular collagen sponge. Osteogenesis was assessed with radiology and histology. Statistical significance was determined by analysis of variance.

Results: No significant difference in osseous healing was observed among empty controls (32.8 percent), acellular collagen sponge alone (34.4 percent), adipose-derived stem cells on acellular collagen sponge (33.9 percent), and osteoinduced adipose-derived stem cells on acellular collagen sponge (40.2 percent). Defects reconstructed with recombinant human BMP-2/acellular collagen sponge were on average 96.9 percent ossified, significantly (p < 0.05) more than the defects in all other groups.

Conclusions: BMP-2–based tissue engineering is a viable approach to craniofacial reconstruction. Adipose-derived stem cells did not significantly augment this process as modeled here. Advances in the understanding of craniofacial biology, and of protein- and cell-based therapies, will enhance the efficacy of tissue-engineering strategies for this problem in the future.

Pittsburgh, Pa.

From the Division of Plastic Surgery, University of Pittsburgh.

Received for publication December 7, 2010; accepted May 18, 2011.

Disclosure:The authors have no financial disclosures.

Joseph E. Losee, M.D.; Division of Pediatric Plastic Surgery, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Suite Floor 3, Pittsburgh, Pa. 15224,

©2011American Society of Plastic Surgeons