Abstract
The tooth is an ectodermal organ that arises from a tooth germ under the regulation of reciprocal epithelial-mesenchymal interactions. Tooth morphogenesis occurs in the tooth-forming field as a result of reaction-diffusion waves of specific gene expression patterns. Here, we developed a novel mechanical ligation method for splitting tooth germs to artificially regulate the molecules that control tooth morphology. The split tooth germs successfully developed into multiple correct teeth through the re-regionalisation of the tooth-forming field, which is regulated by reaction-diffusion waves in response to mechanical force. Furthermore, split teeth erupted into the oral cavity and restored physiological tooth function, including mastication, periodontal ligament function and responsiveness to noxious stimuli. Thus, this study presents a novel tooth regenerative technology based on split tooth germs and the re-regionalisation of the tooth-forming field by artificial mechanical force.
Highlights
The two split tooth germs were equivalent to two tooth germs that are associated during natural tooth development, except that the crown width of each split tooth germ was about half that of natural tooth germs (Fig. 1c)
Tooth germs that were ligated at ED14.5 were able to develop into correctly divided tooth germs that resulted in natural tooth development (Supplementary Fig. 1a,b)
We demonstrated the generation of multiple teeth by splitting tooth germs based on a re-regionalisation of the tooth-forming field, which is controlled by a reaction-diffusion model under artificial manipulation
Summary
Acquired tooth loss in adults from dental caries, periodontal disease or trauma can be managed using conventional dental treatments involving artificial teeth, such as fixed dental bridges, removable dentures and dental implants[19,20] These artificial dental therapies have been widely applied to correct tooth loss, further technological improvements based on biological findings are expected to restore physiological tooth function[21]. Previous studies of autologous tooth germ transplantation, showing that this process prevented immunological rejection after transplantation, have reported successful tooth eruption into the oral cavity and restoration of physiological tooth function[22,23,24] Another method of functional tooth replacement has been demonstrated and is attractive: bioengineered tooth germs have been reconstructed using transplanted tooth-germ-derived stem cells[25,26]. This study reports a technological development based on biological mechanisms that can increase the number of available tooth germs for tooth germ transplantation
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