Regenerative surgery in cranioplasty revisited: the role of adipose-derived stem cells and BMP-2.

Abstract

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. 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. 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. 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.