j endod 2008;36:536–541 before 2004 : apexification : apexification has proven to be highly...

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J Endod 2008;36:536–541

Before 2004 :Apexification : Apexification has proven to be highly

predictable increased susceptibility to cervical

fracture

The artificial apical barrier technique

The material of choice : MTA The technique is predictable and

successful Mineral trioxide aggregate (MTA) was introduced in 1993 by Loma Linda University, the commercial version of MTA introduced in 1998 tooth-colored MTA was

introduced in 2002

first revascularization research efforts :

immature tooth was treated with irrigation and disinfection using two antimicrobial agents (metronidazole and ciprofloxacin) with successful revascularization

Banchs and Trope2004

Application of Tissue Engineering to Regeneration ofPulp and Dentin in Endodontics

Tissue engineering

Stem Cell Therapy

Gene Therapy

Reference

Stem Cell Therapy

key elements of tissue engineering

stem cells

Morphogens or Signaling molecules

scaffold of extracellular matrix

Adult Stem/Progenitor Cells

they exist as undifferentiated cells and maintain this phenotype

they have an ability to self-replicate for prolonged periods

they maintain their multiple differentiation potential throughout the life of the organism

Barry FP. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res Part C, Embryo Today Rev 2003;69:250 –6.

Reference

Stem cell plasticity

capacity and potential for adult stem cells to differentiate into a wider spectrum of phenotypes

fusion of stem cells with endogenous tissue-specifi c cells

Stem cells of dental origin

dental pulp stem cells (DPSCs) stem cells from human exfoliated

deciduous teeth (SHED)

stem cells from the apical papilla

dental follicle progenitor cells

periodontal ligament stem cells

Scaffold

biological three-dimensional microenvironment for cell growth and differentiation

promoting cell adhesion, and migration.

serves as a carrier for morphogen in protein therapy

Scaffold

should be effective for transport of nutrients, oxygen, and waste.

It should be gradually degraded and replaced by regenerative tissue

They should have biocompatibility, nontoxicity, and proper physical and mechanical strength

Signaling molecules

The morphogenetic signaling networks include the five major :

bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs) wingless and int-related proteins (Wnts) Hedgehog proteins (Hhs) tumor necrotic factor (TNF) families

Although five distinct families of morphogens are involved inembryonic tooth development, BMPs appear to be sufficient for toothregeneration in adults

Signaling molecules

BMP2, BMP4, BMP6, BMP7, and Gdf11 are also expressed during odontoblast differentiation

BMP4 and Bmp5 during ameloblast differentiation

Signaling molecules

There are many similarities between morphogenic factors

regulating dentinogenesis and the factors that regulate

reparative dentinogenesis

transforming growth factor ß, (BMPs), platelet-derived

growth factor, fibroblast growth factor, and vascular

endothelial growth factor (VEGF) are incorporated into the

dentin matrix during dentinogenesis and are retained there

As “fossilized” molecules.

Signaling molecules

interestingly, calcium hydroxide has been shown to solubilize Dentin and allow The release Of bioactive molecules that can potentially regenerate dentin.

Sakai VT, Zhang Z, Dong Z, Neiva K, Machado M, Shi S, SantosC, Nör JE. SHED differentiate into functional odontoblasts andendothelium. J Dent Res 2010;89:791–6.

recently observed that SHED have the potential to differentiate into functional vascular endothelial cells via a process that closely resembles that of vasculogenesis

VEGF induces the differentiation of DPSCs (i.e., SHED) into endothelial cells

Vasculogenesis

Reference

Nerve Regeneration

It is noteworthy that members of the BMP family have pronounced effects on neurogenesis

Thus, it is likely BMPs can be used for regenerative pulpal therapy and dentinogenesis may have concurrent beneficial effects on nerve regeneration.

Lein P, Guo X, Hedges AM, Rueger D, Johnson M, Higgins D. The effects of extracellular matrix and osteogenic protein-1 on the morphological differentiation of rat sympathetic neurons. Int J Dev Neurosci 1996;14:203–15.

Adler J, Jayan A, Melia CD. A method for quantifying differential expansion within hydrating hydrophilic matrixes by tracking embedded fluorescent microspheres. J Pharm Sci 1999;88:371–7.

Mabie PC, Mehler MF, Kessler JA. Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype. J Neurosci 1999; 19:7077– 88.

White PM, Morrison SJ, Orimoto K, Kubu CJ, Verdi JM, Anderson DJ. Neural crest stem cells undergo cell-intrinsic development changes in sensitivity to instructive differentiation signals. Neuron 2001;29:57–71.

Refe

renc

es

Complication

There is a risk of unfavorable transformation of the stem cells, and there is also a risk of unwanted contamination of these cells with pathogens during these procedures.

The field of stem cell-based regenerative dentistry is complex and multidisciplinary by nature. Progress will depend on the collaboration between clinicians and researchers from diverse fields (e.g., biomaterials, stem cell biology, endodontics) working together toward the goal of developing biological approaches to regenerate dental and craniofacial tissues.

Treatment procedure

begins with chemical disinfection by copious irrigation of the root canal space with NaOCl, combination of NaOCl/chlorhexidine or NaOCl/hydrogen peroxide

followed by placement of an intracanal medicament at the first visit. Several medicaments like triple antibiotic mixture (metronidazole, ciprofloxacin, and minocycline), calcium hydroxide, and formocresol have been used successfully.

At the next visit

which should be at least 1 week after the initial session or more

in the absence of clinical signs of inflammation, the clinician removes the intracanal medicament

induces bleeding inside the root canal space by irritating the periradicular tissue.

After clot formation, the clinician seals the root canal space by placing an MTA plug over the blood clot

J Endod

2012;38:

1428–

1434

Case Report

An 11-year-old boy

maxillary second premolar tooth had been accidently extracted

and immediately replanted developed pulpal

necrosis and symptomatic apical periodontitis.

After preparing an access cavity, its necrotic pulp was

removed. The canal was irrigated with 5.25% NaOCl solution

and dried with paper points. A triple antibiotic mixed with

distilled water was packed in the canal and left for 22 days.

Twenty milliliters of whole blood was drawn from the

patient’s forearm for preparation of PRP.

After removal of the antibiotic mixture, the PRP was

injected into the canal space up to the cementoenamel

junction level. Three millimeters of grey mineral trioxide

aggregate was placed directly over the PRP clot.

Three days later, the tooth was double-sealed with

permanent filling materials.

RESULTS

Clinical examination 5 1/2 half months later revealed no sensitivity to percussion or palpation tests.

Radiographic examination of this tooth showed resolution of the periapical lesion, further root development, and continued apical closure.

Sensitivity tests with cold and an electric pulp test elicited a positive response similar to those found in the first premolar tooth

Unfavorable outcomes

Discoloration : use of minocycline in the triple antibiotic paste

Treatment Period: The required time for disinfection of the root canal space with triple antibiotic paste or calcium hydroxide and increased number of clinical sessions

J Endod

2012;38:

1428–

1434

Unfavorable outcomes

Challenging Histologic Outcomes: generated tissue inside the root canal space after regenerative endodontic treatment was basically ingrowth of periodontal connective tissue instead of pulpal connective tissue.

No odontoblastic cell layer,dentin-like structure, and pulp-like tissue were detected

3 types of tissues: cementum-like tissue that was responsible for increase in root length and thickness, bone-like tissue and periodontal ligament (PDL)–like tissue inside the canal space

Unfavorable outcomes

Poor Root Development :absence of increase in root wall thickness , or lack of formation of tooth apex

Insufficient Bleeding

Root Canal Calcification/Obliteration

Case report

A healthy 14-year-old female

history of impact trauma to the anterior maxillary teeth 6 years before initial visit

Clinical examinations revealed extensive caries of tooth #8

Both teeth showed normal mobility

Cold test by using Endo-Frost cold spray did not elicit any response in maxillary central incisors

whereas maxillary lateral incisors responded normally to the test

maxillary central incisors were sensitive to percussion and palpation

After local anesthesia with 3% plain mepivacaine

access cavities on teeth #8 and #9 were prepared

Each root canal was passively irrigated with 20 mL NaOCl 5.25% without instrumentation, Canals were gently dried with paper points

A triple antibiotic mixed with distilled water was packed in the canal and left for 4 weeks

A sterile size 40 K-file was overextended and initiate bleeding

approximately 3 mm of MTA was placed in the coronal third of the canals

The patient was recalled yearly

The teeth were not sensitive to percussion and palpation.

The response to the cold test was negative in all follow-up sessions.

In radiographic examinations the radiolucent lesions healed, and the apices formed.

However, there was no increase in the length and thickness of the roots

Six years after initial treatment the patient complained about the appearance of her maxillary central incisors.

severity of discoloration, full crown restoration for both teeth was suggested

root canal therapy of both central incisors

In the present case, passage of a long time (6 years) without any treatment after traumatic impact might be related to damaged Hertwig epithelial root sheath and, subsequently, decreased root development potential

J Endod

2012;38:

1428–

1434

NEW WINDOW FOR FUTURE

Thanks for your attention