Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model (original) (raw)

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. Oral functions, including mastication, swallowing and pronunciation, are indispensable for adequate general health, social activity and quality of life 1. These functions are carried out by the teeth, masticatory muscles and temporomandibular joint under the control of the central nervous system 2,3. The tooth is an ectodermal organ whose development is regulated by reciprocal epithelial-mesenchymal interactions, and the tooth comprises both distinctive hard tissue (e.g., enamel, dentin and cementum) and soft connective tissues (e.g., pulp and periodontal ligaments, including peripheral nerve fibres and blood vessels) 4-6. The physiological functions of teeth, such as masticatory potential, response to mechanical stress and perceptive potential for noxious stimuli, are efficiently carried out by the characteristic three-dimensional multicellular structure that establishes functional harmonization with the maxillofacial region 2,3. Tooth loss due to dental caries, periodontal disease and traumatic injury causes fundamental oral and general health problems related to oral function and associated general health issues.