‫‪REGENERTION‬‬

‫‪ENDODONTICS‬‬

‫‪:‬إعداد الطالبات‬
‫مالك المليكي‬
‫منال الجرفي‬
‫ليلى امين‬
‫‪:‬إشراف الدكتور‬
‫خولة نجم الدين‬
‫منال النهاري‬
‫مختار اآلنسي‬
‫مشاعل الحماطي‬
‫روان الثاليا‬
‫علياء الحوشبي‬ ‫‪1‬‬

‫فاطمة الطيري‬
‫هند المزيجي‬
Regenerative Endodontics: “biologically based procedures designed to re-

place damaged structures, including dentin and root structures, as well as

cells of the pulp-dentin complex .

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Potential methods for regenerating an entire tooth.

The first approach: seeding appropriate stem cells onto scaffolding materials

with the addition of specific growth factors and/or signalling molecules.

The second approach: replicating the natural developmental processes of em-

bryonic tooth formation. Artificial tooth germs are transplanted into the bodies

of animal hosts where there is enough blood flow to support tissue formation.

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 Triad of Regenerative Endodontics

Regenerative Endodontics Control of inflammation Stem

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Stem cells Stem cells Adult /Postnatal Embryonic/Fetal A stem cell is commonly defined

as a cell that has the ability to continuously divide and produce progeny cells that dif-

ferentiate into various other types of cells or tissues

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Adult Stem cells

Autogenic, Allogenic and Xenogenic stem cells Type

• Totipotent • Pluripotent • Multipotent Cell plasticity

• Each cell can develop into a new individual

• Cell can form any cell type (over 200

• Cell differentiated but can form a number of other tissues Source of stem cell

• 1-3 days of embroyonic life • 5-14 days of embruonic life

• Fetal tissue, cord blood, and postnatal stem cells including, dental pulp stem cells

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Pulp Stem Cells A small population of competent progenitor stem cells may exist within

the dental pulp throughout life and are called as pulp stem cells, or, in the case of im-

mature teeth, stem cells from human exfoliated deciduous teeth (SHED) Sometimes

pulp stem cells are called odontoblastoid cells, because these cells appear to synthesize

and secrete dentin matrix like the odontoblast cells they replace.

Source: undifferentiated mesenchymal cells

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One of the most significant obstacles in regenerative endodontics is to ob-

tain stem cells that will continually divide and produce cells or pulp tissues

that can be implanted into root canal systems Possibilities: Development of

an autogenous human pulp stem cell line that is disease- and pathogen-

free:

1. patients do not need to provide their own cells through a biopsy. 2. pulp

tissue constructs can be premade for quick implantation when they are

needed Development of a tissue biopsy transplantation technique (for e.g

using cells from the oral mucosa)

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2. Growth factors: Growth factors are proteins that bind to receptors on the cell and

induce cellular proliferation and/or differentiation GF + Stem cells = increased prolif-

ereation & differentiation For e.g.

TGF Beta and Recombinant human BMP2 stimulates differentiation of adult pulp stem

cells into an odontoblastoid morphology (Roberts-Clark DJ, Smith AJ. Angiogenic

growth factors in human dentine matrix.

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Recombinant BMP-2, -4, and -7 has shown to induce formation of reparative dentin in vivo (

Nakashima M, et al. Regulatory role of transforming growth factor-beta, bone morphogenetic pro-

tein-2, and protein-4 on gene expression of extracellular matrix proteins and differentiation of den-

tal pulp cells. Dev Biol 1994;162:18 –28.) 

The application of recombinant human insulin-like growth factor-1 together with collagen has

been found to induce complete dentin bridging and tubular dentin formation .

This indicates the potential of adding growth factors in regenerative endodontics and also before

pulp capping to stimulate dentin and pulp regeneration.

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Scaffolds: For tissue engineering therapy, pulp stem cells must be organized into a 3

dimensional structure that can support cell organization.

It can be achieved using a porous polymer scaffold seeded with pulp stem cells

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Scaffolds are three-dimensional (3D) porous solid biomaterials designed which

1. Provide a spatially correct position of cell location

2. Promote cell-biomaterial interactions, cell adhesion, and matrix deposition

3. Permit sufficient transport of gases, nutrients, and regulatory factors to allow cell survival, prolifera-

tion, and differentiation

4. Biodegrade at a controllable rate that approximates the rate of tissue regeneration

5. Provoke a minimal degree of inflammation or toxicity in vivo.

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Ideal requirements of a scaffold

1. A high porosity and an adequate pore size are necessary to facilitate cell seeding and diffusion

throughout whole structure of both cells and nutrients

2. Should allow effective transport of nutrients, oxygen, and waste

3. Biodegradability is essential, since scaffolds need to be absorbed by the surrounding tissues without

the necessity of surgical removal.

4. The rate at which degradation occurs has to coincide with the rate of tissue formatiom.

5. Should be biocompatible.

6. Should have adequate physical and mechanical strength.

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Types of scaffolds:

Scaffolds Natural. (Derivatives of extracellular matrix)

1. Proteolytic

2. 2.polysaccharide Synthetic (Polyster) PLA,PGA,PCL,

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Potential Technologies for Regenerative Endodontics

1. Root Canal Revascularization via Blood Clotting

2. Postnatal Stem Cell Therapy

3. Pulp Implantation

4. Injectable Scaffold Delivery

5. Gene Therapy

6. Three-Dimensional Cell Printing

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Root canal revascularization :Apexification: “method to induce a calcified bar-

rier in a root with an open apex” apexification does not attempt to regain vital

tissue in the canal space. The outcome of an apexification procedure is estab-

lishment of an apical barrier against which an obturating material may be

placed

Apexogenesis: “a vital pulp therapy procedure performed to encourage contin-

ued physiologic development and formation of the root end.” Apexogenesis is

indicated for teeth in which there has been no loss of vascularity, thus no need to

“revascularize” the canal space

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A comparison between regenerative endodontic treatment and other pulp treatment procedures In apex-

ification with Ca(OH)2

1. Chances of root fracture and stem cell toxicity.

2. 2. at least 6 months are required to create an apical barrier, and mulitple visits are needed to replen-

ish calcium hydroxide. Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a

root canal dressing may increase risk of root fracture. Dent Traumatol

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MTA is used in the one or two step apexification procedure, and therefore a fewer

number of appointments are needed. Bose R, Nummikoski P, Hargreaves K. A retro-

spective evaluation of radiographic outcomes in immature teeth with necrotic root

canal systems treated with regenerative endodontic procedures

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Apexification with calcium hydroxide Long time span of the entire treat-

ment Multiple visits Increased risk of tooth fracture due to long-term ap-

plication of Ca(OH)2 Apexification with MTA One- or two-step apexifica-

tion Neither strengthens the root nor promotes further root development

Roots remain thin and fragile Revascularization Promotes further root de-

velopment Causes reinforcement of dentinal walls by deposition of hard tis-

sue (strengthening the root against fracture) the characteristics of three

treatment procedures for immature root formation

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Revascularization Apexification with MTA Apexification with calcium hydroxide

Root width 28.2% 0.00% 1.52% Root length 14.9% 6.1% 0.4% The percentage

increase in root width and root length after the treatment procedure Jeeruphan T,

Jantarat J, Yanpiset K, Suwannapan L, Khewsawai P, Hargreaves KM. Mahidol

study 1: comparison of radiographic and survival outcomes of immature teeth

treated with either regenerative endodontic or apexification methods: a retrospec-

tive study. J Endod.

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Pulp revascularization = induction of angiogenesis in endodontically-

treated root canal

Pulp regeneration = pulp revascularization + restoration of functional

odontoblasts and/or nerve fibers

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Revascularization protocol

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Case selection  “This treatment should be considered for the incompletely developed

permanent tooth that has an open apex and is negative to pulpal responsiveness testing

Although the ultimate goal of this approach is to develop a tissue engineering–based

method of pulpal regeneration in the fully developed permanent tooth, it should be rec-

ognized that current revascularization protocols have not been developed or evaluated

for these more challenging cases.” Cohen 10th edition

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During the first appointment  Minimal instrumentation by the use of a small file (de-

termine the working length)  Copious and slow irrigation with 20 ml of NaOCl (lower

concentration) followed by 20 ml of 0.12% to 2% chlorhexidine (CHX), slow irrigatin

with closed end side vented needle kept at the apex .  The root canal system is then

dried with sterile paper points, and the antimicrobial medicament is delivered into the

root canal space.

The best available evidence supports the use of either a triple antibiotic paste or

Ca(OH)2. Both medicaments have been shown to be effective .

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The triple antibiotic paste has the advantage of being a very effective antibiotic combination

against odontogenic microorganisms but carries a potential for minocycline staining of the

crown. Sato I, Ando-Kurihara N, Kota K, Iwaku M, Hoshino E: Sterilization of infected root-

canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocy-

cline in situ. Int Endod J 29:118, 1996  Alternatively, Ca(OH)2 has the advantage of being

widely available and is a commonly used medicament, but it may be cytotoxic to stem cells.

Lai WH, Chen YH, Chiang CP: Regenerative endodontic treatment for necrotic immature

permanent teeth. J Endod 35:160, 2009  After antimicrobial medicament is placed, the tooth

is then sealed with a sterile spon…

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On the second visit:  patient is evaluated for resolution of any signs or symptoms of an acute infection

(e.g., swelling, sinus tract, pain, etc.) that may have been present at the first appointment. The antimi-

crobial treatment is repeated if resolution has not occurred.  Since revascularization-induced bleeding

will be evoked at this appointment, the tooth should not be anesthetized with a local anesthetic contain-

ing a vasoconstrictor. Instead, 3% mepivacaine can be used, which will facilitate the ability to trigger

bleeding into the root canal system  the tooth should be copiously and slowly irrigated with 20 ml

NaOCl, together with gentle agitation with a small hand file to remove the antimicrobial medicament.

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After drying the canal system with sterile paper points, a file is placed a few mm beyond the apical

foramen, and the apical tissue is lacerated with bleeding up to 3 mm from the CEJ.  A small piece of

Colla-Plug (resorbable matrix) may be inserted into the root canal system to serve as a resorbable ma-

trix to restrict the positioning of the MTA.  About 3 mm of MTA is then placed, followed by a restora-

tion. 

A 12- to 18-month recall should be considered as the earliest time point to conduct the clinical examina-

tion and evaluate continued radiographic improvement in root development. Bose R, Nummikoski P,

Hargreaves K: A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root

canal systems treated with regenerative endodontic procedures. J Endod 35:1343, 2009.

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Medicaments being used in cases of revascularization

1. Triple antibiotic paste (1 : 1 : 1 mixture of ciprofloxacin/metronidazole/minocycl

2. 2. Ca(OH)2 alone or in combination with antibiotics,

3. Formocresol

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