Previous studies have shown that tyrosine based E1001-1K scaffolds can promote mineralized tissue formation. Here we will test whether E1001-1K scaffolds can support the formation of alveolar bone, the specialized type of jaw bone that supports dentition. Our approach involves seeding E1001-1K scaffolds with cultured dental stem cells (DSCs) derived from extracted human wisdom teeth, followed by developmental in vitro and in vivo characterizations of alveolar bone, dentin, pulp, periodontal ligament, and enamel tissue formation. Our approach is unique in that we use neural crest cell (NCC) derived dental pulp stem cells that naturally form alveolar jaw bone and tooth tissues. In contrast, mesenchymal stem cells (MSCs), commonly used for craniofacial reconstructions, are derived from the embryonic mesoderm, and do not naturally form alveolar bone, whose specialized architecture can withstand the strong mechanical forces of mastication. The ability to successfully engineer functional, durable alveolar jaw bone would be a significant improvement over current craniofacial repair techniques using bone grafts from non-NCC derived bone (fibula, rib, etc.), which eventually resorb over time. To date we have performed in vitro characterizations of DSC-seeded E1001-1K scaffolds. To continue these promising studies, here we propose studies to validate the formation of alveolar jaw bone and tooth tissues in situ, using a rat, and a rabbit mandible critical sized defect repair model. The successful completion of the proposed studies will allow us to move forward to a large animal mini-pig mandibular defect repair model, prior to pre-clinical human trials.
Supported by the Osteo Science Foundation