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tooth units, is required for the functional recovery of perceptive potential against
noxious stimuli in future tooth regenerative therapy (Luukko et al. 2005 ). Our stud-
ies have demonstrated that sensory and sympathetic nerve fibres can innervate both
the pulp and the PDL region of an engrafted bioengineered tooth (Ikeda et al. 2009 ;
Oshima et al. 2011 ) (Fig. 5.6). Bioengineered teeth offer the potential for pain stim-
uli perception due to pulp injury and orthodontic movement and the potential to
properly transduce these peripheral stimulations to the central nervous system
through c-Fos immunoreactive neurons (Ikeda et al. 2009 ; Oshima et al. 2011 ).
These findings indicate that bioengineered teeth can restore the proprioceptive
responses to noxious stimuli within the maxillofacial region (Fig. 5.7).
Regenerated teeth developed from bioengineered germs or transplanted bio-
engineered mature tooth units have successfully demonstrated the physiological
tooth functions in cooperation with the maxillofacial region such as sufficient
masticatory performance, biological connections via periodontal tissues and afferent
Dental pulp Periodontal ligamentScale bar : 50 μmPDLABD DP
PDLD ABPDLABDPDLABDPDLABDPDLABDD
PD P
D
PD
P
D
PNF/ NPY NF/ CGRP NF/ NPY NF/ CGRPNatural toothErupted bioengineered toothEngraftedBioengineeredtooth unitFig. 5.6 Neural innervation in a bioengineered tooth. The peripheral nerve innervation of the
dental pulp and periodontal ligament area in the natural and bioengineered teeth were represented
by the immunostaining for neurofilament H. Neuropeptide Y (NPY), which is synthesised in sym-
pathetic nerves, was detected in the pulp and the PDL neurons. Furthermore, calcitonin gene-
related peptide (CGRP), which is synthesised in sensory nerves and is involved in sensing tooth
pain, was also observed in both the pulp and the PDL neurons. D dentin; P pulp; PDL periodontal
ligament; AB alveolar bone
M. Oshima and T. Tsuji