Fully functional bioengineered tooth replacement as an organ replacement therapy

doi:10.1073/pnas.0902944106

Fully functional bioengineered tooth replacement as an organ replacement therapy

^aDepartment of Biological Science and Technology, Faculty of Industrial Science and Technology, and
^cResearch Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan;
^bOrgan Technologies Inc., Tokyo 101-0048, Japan;
^dDivision of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi 980-8575, Japan; and
^eOral and Maxillofacial Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8510, Japan

↵¹E.I. and R.M. contributed equally to this work.
Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved June 30, 2009 (received for review March 17, 2009)

Abstract

Current approaches to the development of regenerative therapies have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs which work in cooperation with surrounding tissues to replace organs that were lost or damaged as a result of disease, injury, or aging. Here, we report a successful fully functioning tooth replacement in an adult mouse achieved through the transplantation of bioengineered tooth germ into the alveolar bone in the lost tooth region. We propose this technology as a model for future organ replacement therapies. The bioengineered tooth, which was erupted and occluded, had the correct tooth structure, hardness of mineralized tissues for mastication, and response to noxious stimulations such as mechanical stress and pain in cooperation with other oral and maxillofacial tissues. This study represents a substantial advance and emphasizes the potential for bioengineered organ replacement in future regenerative therapies.

Footnotes

²To whom correspondence should be addressed. E-mail: t-tsuji{at}rs.noda.tus.ac.jp
Author contributions: T.T. designed research; E.I., R.M., and K.N. performed research; E.I., K.N., T.T.-Y., and S.K. contributed new reagents/analytic tools; E.I., R.M., K.N., K.I., T.N., M.O., and M.M. analyzed data; and E.I., R.M., K.N., and T.T. wrote the paper.
Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved June 30, 2009
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Freely available online through the PNAS open access option.