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