Abstract
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.
Highlights
IntroductionOsseo-integrated dental implants, which can restore occlusal function without injuring the adjacent teeth, have been used to treat tooth loss[9,10]
To restore occlusal function or address aesthetic problems after tooth loss, conventional dental therapies that replace the tooth with artificial materials, such as fixed dental bridges and removable dentures, are commonly used[7,8]
By contrast, bioengineered tooth generation occurred with a frequency of 100% in the reconstructing conditions of epithelial tissue and mesenchymal tissue, epithelial cells and mesenchymal tissue, and epithelial tissue and mesenchymal cells that were isolated from deciduous third molar and permanent first molar (M1) tooth germs (Table 1 and Supplemental Fig. 1)
Summary
Osseo-integrated dental implants, which can restore occlusal function without injuring the adjacent teeth, have been used to treat tooth loss[9,10] These artificial therapies have been widely applied in dental rehabilitation, further technological developments based on biological findings are necessary to restore the physiological functions of teeth[6]. A fully functional bioengineered tooth replacement with adequate structure, masticatory function, responsiveness to mechanical stress and perceptive potential for noxious stimulation was recently demonstrated in a murine tooth-loss model[21,22]. It is expected that future whole-tooth restoration in humans will be realized via the autologous transplantation of bioengineered tooth germ reconstructed using a patient’s own stem cells[6,22]. This study highlights the feasibility of fully functional tooth restoration by autologous transplantation of bioengineered tooth germ
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