Organ Regeneration Based on Developmental Biology

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(Finkelman et  al. 1990 ; Cassidy et  al. 1997 ; Roberts-Clark and Smith 2000 ;
Zhao et al. 2000 ; Sloan and Smith 1999 ; Dobie et al. 2002 ; Lovschall et al. 2001 ;
Tziafas et  al. 1998 ; Tziafas and Papadimitriou 1998 ; Hu et  al. 1998 ; Rutherford
et al. 1993 ; Jepsen et al. 1997 ; Cooper et al. 2010 ) (Fig. 5.2a).
Periodontal tissue often suffers irreversible inflammation caused by periodontal
disease or excessive occlusal force; however, the effective treatments for periodon-
tal tissue regeneration have not yet been established. Several molecular approaches
can be administered via the local application of human recombinant cytokines, such
as platelet-derived growth factor (PDGF), IGFs, brain-derived neurotrophic factor
(BDNF) and bFGF, to accelerate periodontal regeneration (Marcopoulou et  al.
2003 ; Raja et al. 2009 ; Dereka et al. 2006 ). Furthermore, periodontal tissue is com-
posed of an extracellular matrix that contains collagen fibres and microfibrils, which
play a critical role in periodontal tissue formation. Recently, it was reported that the
local administration of a fibrillin-1-associated protein, ADAMTSL6β, accelerated
wound healing in periodontal tissues by accumulating microfibrils (Tsutsui et  al.
2010 ; Saito et al. 2011 ) (Fig. 5.2a).


5.3.3 Bioengineered Root Regeneration by Tissue Engineering


Technology


Dental implants, which can be stand alone in the jawbone unlike conventional den-
tal treatments with the invading adjacent teeth, have been widely applied for the
rehabilitation of tooth loss (Burns et al. 2003 ; Petrie et al. 2009 ). However, because
of the absence of the natural periodontal tissue, the currently available dental
implant that is directly connected to the surrounding alveolar bone cannot exhibit
biological tooth functions, such as the reduction of excessive occlusal force, orth-
odontic tooth movement via bone remodelling and the ability to perceive noxious
stimuli (Brenemark and Zarb 1985 ; Burns et  al. 2003 ). In order to regenerate the
tooth root including periodontal tissues for maintaining physiological tooth func-
tions, a stem cell-based tissue engineering application has been attempted. A unique
approach for tooth root regeneration employing a root-shaped hydroxyapatite/tri-
calcium phosphate (HA/TCP) carrier loaded with gelfoam/PDLSC-covered SCAP
cells has been reported (Sonoyama et  al. 2006 ; Wei et  al. 2013 ) (Fig. 5.2b). This
tissue engineering technology generated a bioengineered tooth root using a combi-
nation of tooth root and periodontal tissues, and it may contribute to establish the
next-generation dental regenerative technology that will integrate stem cell-
mediated tissue regeneration, biomaterial engineering and current dental treatment.
The root regeneration approach is expected to be applied in the clinic more early
compared to the whole-tooth regeneration methods.


M. Oshima and T. Tsuji
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