Whole Tooth Regeneration Using a Bioengineered Tooth - New Trends in Tissue Engineering and Regenerative Medicine - page 112

Figure 2. Strategies for whole tooth replacement via regenerative therapies. Functioning teeth can now be regenerat‐
ed in vivo by transplanting bioengineered tooth germ generated from epithelial and mesenchymal cells via the organ
germ method, or bioengineered tooth units with periodontal ligament and alveolar bone developed from bioengi‐
neered tooth germ.
In addition, the cell aggregation method, which aims to reconstitute a bioengineered organ
germ, has been applied for the transplantation of cell aggregates constructed from dental
epithelial and mesenchymal cells, and it has been reported that this approach can generate
appropriate tooth formation (Hu et al., 2006). It has also been reported that mixed cell aggre‐
gates of tooth germ-derived epithelial and mesenchymal cells can develop into a tooth with
the correct structure, following epithelial cell sorting and subsequent self-organisation of the
epithelial and mesenchymal cells (Song et al., 2006). However, these approaches suffer from
critical limitations, including a low frequency of tooth formation and irregularity of the
resulting tooth tissue structures, for example with enamel-dentin complex formation and the
arrangements of the ameloblast/odontoblast cell lineages.
To achieve precise replication of the processes in organogenesis, an in vitro three-dimensional
novel cell manipulation method designated as the bioengineered organ germ method has been
developed (Nakao et al., 2007). This innovative method is based on compartmentalisation of
the epithelial and mesenchymal cells at a high-cell density in a type I collagen gel (Fig. 3A).
Bioengineered tooth germ created by this technique, which could allow for large-scale organ
development, mimics the multicellular assembly underlying epithelial-mesenchymal interac‐
tions during natural tooth development. This bioengineered tooth germ generates a correct
tooth structure after transplantation in an organ culture in vitro as well as following placement
into a subrenal capsule in vivo . The bioengineered tooth germ generated by this method was
also found to develop in the oral cavity to form the proper tooth structure (Nakao et al.,
2007). Furthermore, this unique technology can successfully generate a size-controlled