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Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement

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Abstract

Oral and general health is compromised by irreversible dental problems, including dental caries, periodontal disease and tooth injury. Regenerative therapy for tooth tissue repair and whole-tooth replacement is currently considered a novel therapeutic concept with the potential for the full recovery of tooth function. Several types of stem cells and cell-activating cytokines have been identified in oral tissues. These cells are thought to be candidate cell sources for tooth tissue regenerative therapies because they have the ability to differentiate into tooth tissues in vitro and in vivo. Whole-tooth replacement therapy is regarded as an important model for the development of an organ regenerative concept. A novel three-dimensional cell-manipulation method, designated the organ germ method, has been developed to recapitulate organogenesis. This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial–mesenchymal interactions. A bioengineered tooth germ can generate a structurally correct tooth in vitro and erupt successfully with the correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was successfully engrafted into an adult jawbone through bone integration. Such bioengineered teeth were able to perform normal physiological tooth functions, such as developing a masticatory potential in response to mechanical stress and a perceptive potential for noxious stimuli. In this review, we describe recent findings and technologies underpinning tooth regenerative therapy.

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Acknowledgments

This work was partially supported by Health and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare (no. 21040101) to Akira Yamaguchi (Tokyo Medical and Dental University), a Grant-in-Aid for Scientific Research (A) (no. 20249078) to T. Tsuji (2008–2010) and a Grant-in-Aid for Young Scientists (B) to M. Oshima from the Ministry of Education, Culture, Sports and Technology, Japan. This work was also partially supported by Organ Technologies Inc.

Conflict of interest

M. Oshima and T. Tsuji have no competing interest.

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Authors and Affiliations

  1. Department of Oral Rehabilitation and Regenerative Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan

    Masamitsu Oshima

  2. RIKEN Center for Developmental Biology, Kobe, Hyogo, 650-0047, Japan

    Takashi Tsuji

  3. Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, 278-8510, Japan

    Takashi Tsuji

  4. Organ Technologies Inc., Tokyo, 101-0048, Japan

    Takashi Tsuji

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  1. Masamitsu Oshima
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Correspondence to Takashi Tsuji.

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Oshima, M., Tsuji, T. Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement. Odontology 102, 123–136 (2014). https://doi.org/10.1007/s10266-014-0168-z

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