Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model

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.

A new perspective to push forward a stagnated dental world

“…14,15 In addition, the transplantation of bioengineered teeth has also been achieved in several animals, proving it is possible and feasible to have an engineered tooth germ to develop into a vital, fully-formed tooth with periodontal ligament in situ. 16…”

Three‐dimensional printing biotechnology for the regeneration of the tooth and tooth‐supporting tissues

“…Reconstruction of the tooth germ has shed light on the potential of whole‐tooth regeneration (Ikeda et al, ; Nakao et al, ). The bioengineered tooth germ reconstructed by the group of Takashi erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of natural teeth in postnatal mice and canine models (Nakao et al, ; Ikeda et al, ; Ono et al, ; Oshima & Tsuji, ; Oshima et al, ). Additionally, mimicking such an epithelial–mesenchymal interface that naturally occurs in the early stages of tooth formation has been proven to be the fundamental step in tooth germ regeneration (W. Zhang, Ahluwalia, & Yelick, ; W. Zhang, Vazquez, Oreadi, & Yelick, ).…”

Dental mesenchymal stem cell research—How much will it translate to clinical orthodontics?

“…Until recently, the concept of tooth bioengineering had been limited to rodent models; however, this technique has now been used in a Beagle dog model 46 . This investigation has demonstrated that functional tooth development can be achieved in higher mammals using epithelial and mesenchymal cells; not only derived from embryos, but also from postnatal tooth germs.…”

“…This investigation has demonstrated that functional tooth development can be achieved in higher mammals using epithelial and mesenchymal cells; not only derived from embryos, but also from postnatal tooth germs. This represents an exciting potential model because it offers the possibility of autologous transplantation of engineered teeth in humans, which avoids the problems of immune rejection 46 .…”