Organ Regeneration Based on Developmental Biology

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5.4 Technological Development for Whole-Tooth

Regeneration Utilising a Novel Three-Dimensional

Cell-Manipulation Method

Stem-cell transplantation and cytokine therapy are now considered an effective
approach to restore partial organ functions at local damaged sites. However, these
therapeutic technologies have not yet achieved the ideal goal of reconstructing com-
plex organs which can recover from an extensive organ injury or a severe organ
dysfunction. The ultimate goal of regenerative therapy in future is to develop organ
replacement regenerative therapies that will restore lost or damaged tissues with a
fully functioning bioengineered organ (Oshima and Tsuji 2014 ). Current bioengi-
neering technology for regenerating three-dimensional organs has progressed to the
replication of organogenesis through epithelial-mesenchymal interactions that
occur in the developing embryo, thereby enabling the development of fully func-
tional bioengineered organs using bioengineered organ germs that are generated
from immature stem cells via three-dimensional cell manipulation in vitro (Ikeda
and Tsuji 2008 ; Oshima and Tsuji 2014 ). In the dental field, an attractive concept
involves transplanting a bioengineered tooth germ into the tooth-loss region that
would develop into a functioning mature tooth (Nakao et al. 2007 ; Ikeda et al. 2009 )
(Fig. 5.3, upper panel). It is also expected that it will be possible to transplant a
bioengineered tooth unit including a mature tooth, PDL and alveolar bone that
can be physiologically integrated into the alveolar bone of the recipient’s jaw
(Nakao et al. 2007 ; Oshima et al. 2011 ) (Fig. 5.3, lower panel). For the realisation

Transplantation of a

bioengineered tooth unit

Engraftment of a

bioengineered tooth unit

Functional tooth replacement

Generation of

bioengineered

tooth unit

Bioengineered

tooth unit

Functional tooth regeneration

Transplantation of

a bioengineered tooth germ

Eruption of

a bioengineered tooth

Mesenchymal cells

3-D cell manipulation

Epithelial cells Bioengineered

tooth germ

Fig. 5.3 Regenerative concept for whole-tooth replacement. Fully functioning teeth can be regen-
erated in vivo by transplanting bioengineered tooth germs reconstituted from epithelial and mes-
enchymal stem cells via the organ germ method or by transplanting bioengineered tooth units with
a periodontal ligament and alveolar bone that developed from bioengineered tooth germs

5 Functional Tooth Regeneration