Tissue Engineering Strategies to Improve Osteogenesis in the Juvenile Swine Alveolar Cleft Model.

Alveolar (gumline) clefts are the most common congenital bone defect in humans, affecting 1 in 700 live births. Treatment to repair these bony defects relies on autologous, cancellous bone transfer from the iliac crest. This harvest requires a second surgical site with increased surgical time associated with potential complications, while providing only limited cancellous bone. Improvements in treatment protocols that avoid these limitations would be beneficial to patients with clefts and other craniofacial bone defects. There have been steady advances in tissue-engineered (TE) solutions for long-bone defects and adult patients, but advances for the pediatric craniofacial skeleton have been slower to emerge. This study utilizes a previously established juvenile swine model with a surgically created, critical size alveolar defect to test the efficacy of umbilical cord (UC) mesenchymal stem cells (MSCs) treatments on nano-microfiber scaffolds. At 1 month after implanting our TE construct, mineralized tissue in the surgical gap was quantified through computed tomography (CT), and histology, and excised tissue was subjected to mechanical testing. Both undifferentiated and predifferentiated (toward an osteogenic lineage) UC MSCs generated bone within the cleft on a scale comparable to iliac crest cancellous bone, as evidenced by histology and CT scans. All of the pigs treated with scaffold/stem cell combinations had mineralized tissue within the defect, although without filling the entire defect. Several of the experimental animals exhibited poor and/or asymmetric maxillary growth 1 month after the initial surgery, especially if the surgical defect was located on the smaller side of an already asymmetric pig. Our results demonstrate that tissue engineering approaches using UC MSCs are a promising alternative for repair of the alveolar cleft. Data in the pig model demonstrate that implanted scaffolds are at least as good as the current gold standard treatment based on harvesting cancellous bone from the iliac crest, regardless of whether the cells seeded on the scaffold are precommitted to an osteogenic fate.