Dr. Ashok Ayer
Department of Conservative Dentistry &
CODS, BPKIHS, Dharan
Regenerative endodontics: is a biologically based
procedure designed to replace damaged structures,
Dentin and root structures
Cells of the pulp-dentin complex
Vital pulp therapy with pulp stem/progenitor cells
might regenerate dentin-pulp complex without the
removal of the whole pulp.
Caries, pulpitis, and apical periodontitis ultimately
result in premature tooth
diminishing the quality of life
Regeneration of parts of the tooth structure can
prevent or delay the loss of the whole tooth.
The key ingredients for tissue engineering .
Proteins that bind on receptors
on the cell and induce cellular
proliferation & differentiation.
The major domains of research required to develop regenerative endodontic procedures.
Stem cell: ability to;
Continuously divide to either replicate itself
Produce specialized cells than can differentiate into
various other types of cells or tissues
Embryonic stem cells derive from the early mammalian
embryo at the blastocyst stage and have the capability to
give rise to all kinds of cells.(Pluripotent)
Adult /Postnatal stem cells are just multipotent
because their differentiation potential is restricted to
certain cell lineages
DPSCs: multipotency, high proliferation rates and accessibility (2)
(Gronthos et al., 2000) (3)
(Miura et al., 2003) (4)
(Seo et al., 2004) (5)
The scaffold provides a 3D environment
for cells to attach and grow,
(Therefore mimicking the in vivo
collagen, gelatin, dextran and fibronectin.
Polylactic acid (PLA),
Polyglycolic acid (PGA),
Poly lactic-co-glycolic acid (PLGA
The key elements of tissue engineering and dentin regeneration
Laino and co-workers  isolated a selected
subpopulation of DPSCs called;
Stromal bone producing dental pulp stem cells
Which roughly represent 10% of dental pulp cells
These cells display a great capability of selfexpanding and differentiating in pre-osteoblasts;
which are able to self-maintain and renew for long
Role of DPSCs in regenerative dentistry
Pulp tissue is exposed
I. Calcium hydroxide and mineral trioxide aggregate
(MTA), promotes the activity of reparative
II. Bigger traumas or advanced caries are clinically treated
with root canal therapy.
III. Regenerative approaches:
In which diseased or necrotic pulp tissues are removed
Replaced with regenerated pulp tissues
To revitalize the teeth.
The two main strategies for pulp therapy to regenerate dentin: in vivo and ex vivo
methods by application of BMP gene. 
Dentin-pulp complex formation with optimal orientation for clinical application of regenerative therapy. The pulp
stem cells are transduced with BMP gene and attached to a defined scaffold to differentiate into odontoblasts. The
tubular dentin-pulp complex can be transplanted on the exposed or amputated pulp in the cavity. 
Ikeda et al. (2009)
Reported a successful fully functioning tooth replacement in an adult mouse
achieved through the transplantation of bioengineered tooth germ into the alveolar
bone in the lost tooth region.
These results together raise the possibility that a
protocol for pulp tissue regeneration and new dentin
formation for clinical therapeutic purposes could be
It may offer an alternative approach to save teeth that
may have compromised structural integrity.
Peter E. Murray et al. Regenerative endodontics: A review of current
status and a call for action J Endod 2007;33:377-90.
Yamada, Y., Ito, K., Nakamura, S., Ueda, M. & Nagasaka, T. (2010).
Promising cell-based therapy for bone regeneration using stem cells
from deciduous teeth, dental pulp, and bone marrow. Cell
Transplantation. (October 2010)
Gronthos, S., Mangani, M., Brahim, J., Robey, PG. & Shi, S. (2000).
Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.
Proceedings of the National Academy of Sciences of the United States
of America, Vol.97, No.25, (December 2000), pp. 13625- 13630, ISSN
Miura, M., Gronthos, S., Zhao, M., Lu, B., Fisher, LW., Robey, PG. &
Shi, S. (2003). SHED: stem cells from human exfoliated deciduous
teeth. Proceedings of the National Academy of Sciences of the United
Stases of America, Vol.100, No.10, (May 2003), pp.5807-5812, ISSN
5. Seo, BM., Miura, M., Gronthos, S., Bartold, PM., Batouli, S., Brahim, J.,
Young, M., Robey,PG., Wang, CY. & Shi, S. (2004). Investigation of
multipotent postnatal stem cells from human periodontal ligament.
Lancet, Vol.364, No.9429, (July 2004), pp.149-155, ISSN 0140-6736
6. George T.-J. Huang Dental pulp and dentin tissue engineering and
regeneration: advancement and challenge Frontiers in Bioscience E3,
788-800, January 1, 2011
7. Nakashima M. Bone morphogenetic proteins in dentin regeneration
for potential use in endodontic therapy. Cytokine growth factor Rev.
8. Laino, G., D'Aquino, R., Graziano, A., Lanza, V., Carinci, F., Naro, F.,
Pirozzi, G., & Papaccio, G. (2005). A new population of human adult
dental pulp stem cells: a useful source of living autologous fibrous
bone tissue (LAB). Journal of Bone and Mineral Research, Vol.20,
No.8, (August 2005), pp.1394-1402, ISSN 0884-0431
9. The Application of Tissue Engineering to Regeneration of Pulp and
Dentin in Endodontics Misako Nakashima, PhD, DDS, and Akifumi
Akamine, PhD, DDS
10. Nakashima, M. (2005). Bone morphogenetic proteins in dentin
regeneration for potential use in endodontic therapy. Cytokine &
Growth Factor Reviews, Vol.16, No.3, (June 2005), pp.369-376 ISSN
11. Paul C Edwards et al. Gene-enhanced tissue engineering for dental
hard tissue regeneration: (2) dentin-pulp and periodontal
regeneration. Head & Face Medicine 2006, 2:16 . doi:10.1186/1746-160X2-16
12. D’aquino R, De Rosa A, Laino G, Caruso F, Guida L, Rullo R, Checchi V,
Laino L, Tirino V, Papaccio G. 2008. Human dental pulp stem cells:
from biology to clinical applications. J. Exp. Zool. (Mol. Dev. Evol.) 310B
13. Ikeda E, Morita R, Nakao K, Ishida K, Nakamura T, Takano-Yamamoto
T et al. Fully functional bioengineered tooth replacement as an organ
replacement therapy. Proc Natl Acad Sci USA. 2009 Aug;106(32):1347580.