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Expanding Therapeutic Boundaries: Regenerative Endodontics Dr. Ashok Ayer Department of Conservative Dentistry & Endodontics CODS, BPKIHS, Dharan

Expanding therapeutic boundaries: Regenerative Endodontics

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Regenerative Endodontics

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Page 1: Expanding therapeutic boundaries: Regenerative Endodontics

Expanding Therapeutic Boundaries: Regenerative Endodontics

Dr. Ashok AyerDepartment of Conservative Dentistry & EndodonticsCODS, BPKIHS, Dharan

Page 2: Expanding therapeutic boundaries: Regenerative Endodontics

Introduction

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.

Page 3: Expanding therapeutic boundaries: Regenerative Endodontics

Caries, pulpitis, and apical periodontitis ultimately result in premature tooth loss and therefore diminishing the quality of life

Regeneration of parts of the tooth structure can prevent or delay the loss of the whole tooth.

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The major domains of research required to develop regenerative endodontic procedures.

The key ingredients for tissue engineering [1].

Proteins that bind on receptors on the cell and induce cellular proliferation &

differentiation.

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Stem cell: ability to; Continuously divide to either replicate itself

(self-renewing), or

Produce specialized cells than can differentiate into various other types of cells or tissues

(multilineage differentiation)

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

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DPSCs: multipotency, high proliferation rates and accessibility (2)

(Gronthos et al., 2000) (3)

(Miura et al., 2003) (4)

(Seo et al., 2004) (5)

[6]

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The key elements of tissue engineering and dentin regeneration[7]

/Growth factors

The scaffold provides a 3D environment for cells to attach and grow,

(Therefore mimicking the in vivo condition)

collagen, gelatin, dextran and fibronectin.

Polylactic acid (PLA), Polyglycolic acid (PGA), Poly lactic-co-glycolic acid (PLGA

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Laino and co-workers [8] isolated a selected subpopulation of DPSCs called;Stromal bone producing dental pulp

stem cells (SBP-DPSCs) Which roughly represent 10% of dental

pulp cells

These cells display a great capability of self-expanding and differentiating in pre-osteoblasts;

which are able to self-maintain and renew for long time.

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Role of DPSCs in regenerative dentistryPulp tissue is exposed

I. Calcium hydroxide and mineral trioxide aggregate (MTA), promotes the activity of reparative dentinogenesis

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

and Replaced with regenerated pulp tissues

To revitalize the teeth.

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The two main strategies for pulp therapy to regenerate dentin: in vivo and ex vivo methods by application of BMP gene. [7]

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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. [9]

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Developmental approaches for regenerative endodontic techniques [1]

(J Endod 2007;33:377-90)

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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.

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Conclusion:

These results together raise the possibility that a protocol for pulp tissue regeneration and new dentin formation for clinical therapeutic purposes could be established.

It may offer an alternative approach to save teeth that may have compromised structural integrity.

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References:1. Peter E. Murray et al. Regenerative endodontics: A review

of current status and a call for action J Endod 2007;33:377-90. doi:1o.1016/j.joen.2006.09.013

2. 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)

3. 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 0027-8424

4. 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 0027-8424

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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. 2005;16(3):369-76

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 1359-6101

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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:10.1186/1746-160X-2-16

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):13475-80.

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Thank You