75Sharpe and Young 2005 ). It is anticipated that whole-tooth replacement therapy will
be established in the near future as a novel treatment that contributes to functional
recovery by meeting aesthetic and physiological requirements (Volponi et al. 2010 ;
Sharpe and Young 2005 ). Many approaches to replace missing teeth have been
evaluated in the past three decades, including three-dimensionally bioengineered
teeth and tooth germ generation using biodegradable materials and cell aggregation
methods (Volponi et al. 2010 ; Sharpe and Young 2005 ; Duailibi et al. 2006 ; Liu
et al. 2014 ). The first report of a fully functioning bioengineered tooth replacement
with the correct tissue structure, masticatory function, responsiveness to mechanical
stress and perceptive potential following transplantation into a tooth-loss region was
published (Nakao et al. 2007 ; Ikeda et al. 2009 ; Oshima et al. 2011 ). In this chapter,
we will describe the recent findings and technologies for partial tooth-tissue repair
and whole-tooth regeneration in future that can provide functional recovery and
ultimately replace the current dental treatments using artificial materials.
5.2 Tooth Organogenesis
Ectodermal organs, such as the teeth, hair and mammary glands, arise from their
respective organ germs through reciprocal epithelial-mesenchymal interactions.
This interaction is the principal mechanism that regulates almost all organogenesis
via signalling molecules and transcription factors (Bei 2009 ; Nakatomi et al. 2010 ;
Thesleff 2003 ). During early craniofacial development in mice, tooth-forming fields
are specified at embryonic day (ED) 10.5–11.5 by the expression of homeobox
genes, such as Lhx8, Msx1, Msx2 and Barx1, and secretory molecules including
bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs), in the
embryonic jaw (Nakatomi et al. 2010 ; Thesleff 2003 ; Jernvall and Thesleff 2012 ).
At ED 11.5, the oral epithelium elongates into the mesenchymal tissue region, and
then a tooth bud is formed by the condensation of neural crest-derived mesenchymal
tissue (Nakatomi et al. 2010 ; Thesleff 2003 ; Jernvall and Thesleff 2012 ). At
ED13.5–14.5, the first enamel knot, which acts as a transient signalling centre to
orchestrate tooth developmental process by controlling the gene expression of vari-
ous signalling molecules and transcription factors, appears in the dental epithelium.
This signalling centre is thought to regulate individual cell fate and epithelial-
mesenchymal interactions. The secondary enamel knots are formed; these regions
play an important role in regulating the position and number of tooth cusps at
ED16.5 (Nakatomi et al. 2010 ; Thesleff 2003 ; Jernvall and Thesleff 2012 ). After
ED18.5, the epithelial and mesenchymal cells in the tooth germ terminally differen-
tiate into the tooth tissue-forming cells such as ameloblasts and odontoblasts,
respectively. These cells secrete a collagenous extracellular matrix to mineralise
into the enamel or dentin matrix at the interface between epithelium and mesen-
chyme (Fukumoto and Yamada 2005 ). In the same period, the outer mesenchymal
cells around tooth germ form the dental follicle tissue that can generate periodontal
tissue including cementum, periodontal ligaments and alveolar bone (Saito et al. 2009 ).
5 Functional Tooth Regeneration