Application of Tissue Engineering to Regeneration of Pulp

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Transcript Application of Tissue Engineering to Regeneration of Pulp

J Endod 2008;36:536–541
Before 2004 :
Apexification :
 Apexification has proven to be highly
 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
Stem Cell Therapy
Gene Therapy
stem cells
Morphogens or Signaling molecules
scaffold of extracellular matrix
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.
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
biological three-dimensional
microenvironment for cell growth and
promoting cell adhesion, and migration.
serves as a carrier for morphogen in protein
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
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 in
embryonic tooth development, BMPs appear to be sufficient for tooth
regeneration in adults
BMP2, BMP4, BMP6, BMP7, and Gdf11 are
also expressed during odontoblast
BMP4 and Bmp5 during ameloblast
There are many similarities between morphogenic factors
regulating dentinogenesis and the factors that regulate reparative
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.
interestingly, calcium hydroxide has been shown to solubilize
Dentin and allow The release Of bioactive molecules that can
potentially regenerate dentin.
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
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 cellintrinsic development changes in sensitivity to instructive differentiation signals. Neuron 2001;29:57–71.
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.
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
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.
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
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
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
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
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
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
The patient was recalled yearly
The teeth were not sensitive to percussion and
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