Functional tooth regeneration using a bioengineered tooth unit

Objective: To achieve the functional replacement of missing teeth, the strategy has been proposed to develop a bioengineered tooth germ by reproducing the developmental process. We have reported a novel three-dimensional cell processing method to generate bioengineered organ germs (Nature Methods 2007). We further reported fully functioning bioengineered tooth replacement through the transplantation of a bioengineered tooth germ (PNAS 2009). In this study, we also provide a proof of concept that successful tooth replacement through the transplantation of the bioengineered tooth unit.

Methods: We have generated a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone. We investigated whether a bioengineered tooth unit could be engrafted into a properly-sized bony hole in the alveolar bone. We investigated whether an engrafted bioengineered mature tooth unit can also restore physiological tooth functions in vivo, and regenerate the alveolar bone volume of the recipient by extensive bone defect model.

Result: The shape and length of the bioengineered tooth unit could be controlled in three-dimensions using a size-controlling device. The bioengineered teeth could be engrafted into regions of tooth loss through bone integration through natural bone remodeling in the recipient. Engrafted bioengineered tooth restored tooth functions such as masticatory potential, functional responsiveness including bone remodeling of periodontal tissue to accommodate mechanical stress, and the proper responsiveness to noxious stimulations via both peripheral sensory and sympathetic nerves in vivo. Furthermore, transplantation of a bioengineered tooth could be regenerated the alveolar bone significantly in a vertical direction into an extensive bone defect.

Conclusion: These findings indicate the transplantation of a bioengineered tooth unit has the potential for future clinical use to treat tooth loss associated with a serious alveolar bone defect. This study thus represents a substantial advance and demonstrates the potential for bioengineered tooth replacement as a future tooth regenerative therapy.