Porcine allograft mandible revitalization using autologous adipose-derived stem cells, bone morphogenetic protein-2,...

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.

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.

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.

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.