title: Functional tooth restoration utilising split germs through re-regionalisation of the tooth-forming field.
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.
authors.affiliation: Department of Maxillofacial Orthognathics, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8510, JAPAN.|Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.
authors.forename: Naomi
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, JAPAN.|Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.
authors.forename: Chie
authors.initials: C
authors.lastname: Tanaka
authors.affiliation: Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.|Organ Technologies Inc., Tokyo, 108-0074, JAPAN.|RIKEN Center for Developmental Biology, Kobe, Hyogo, 650-0047, JAPAN.
authors.forename: Miho
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.|Department of Clinical Pathophysiology, Tokyo Dental College, Chiyoda-ku, Tokyo, 101-0061, JAPAN.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.|Department of Physics and Mathematics, College of Science and Engineering, Aoyama Gakuin University, Sagamihara, Kanagawa, 252-5258, JAPAN.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Department of Maxillofacial Orthognathics, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8510, JAPAN.
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.|Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, JAPAN.|Organ Technologies Inc., Tokyo, 108-0074, JAPAN.|RIKEN Center for Developmental Biology, Kobe, Hyogo, 650-0047, JAPAN.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000235:genetics / Q000502:physiology; D003793:Dental Restoration, Permanent / Q000379:methods*; D003794:Dental Restoration, Temporary / Q000379:methods*; D015870:Gene Expression / Q000235:genetics; D017403:In Situ Hybridization; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009805:Odontogenesis / Q000235:genetics / Q000502:physiology*; D010513:Periodontal Ligament / Q000378:metabolism / Q000502:physiology / Q000601:surgery; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014070:Tooth / Q000378:metabolism / Q000502:physiology* / Q000601:surgery; D014083:Tooth Germ / Q000378:metabolism / Q000502:physiology* / Q000601:surgery