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Endo Journal Review

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    Endodontic Journal Review

    Presenter: PGY1

    Date: 2013.07.30

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    RevascularizationOdontoblastic

    layersInnervation

    Pulp Regeneration

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    Stem/ProgenitorCells

    ScaffoldGrowthFactors

    Principles of

    Tissue

    Engineering

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    Regenerative Endodontic Treatment of

    Permanent Teeth

    after Completion of Root Development:A Report of Two Cases

    Paryani et al, J Endod 2013

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    CASE PRESENTATION

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    Case 1 Case 2

    General

    Data

    14 y/o girl presented on

    August 5, 2010

    11 y/o girl presented on

    September 2, 2010

    Chief

    Complain

    Pain on her upper front

    tooth for 3 or 4 days.

    The pain was constant

    but not severe

    Pain on her upper front

    tooth

    Present

    Illness

    Emergency treatment

    was done

    Emergency patient

    Medical

    History

    Noncontributory Noncontributory

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    Case 1 Case 2

    ExtraoralExamination

    Non significant Non significant

    Intraoral

    Examination

    Tooth 11

    Uncomplicated crown

    fracture with a largetemporary restoration

    on palatal surface

    Cold test: (-)

    Percussion (+)

    Palpation (-) PD: 5 mm in palatal

    gingiva

    Mobility: normal

    Tooth 21

    Uncomplicated crown

    fracture with anexisting composite

    restoration

    Cold test: (-)

    Percussion (-)

    Palpation (-) PD: WNL

    Mobility: normal

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    Case 1 Case 2X-ray Periradicular

    rarefaction along mesial

    aspect of the root with

    closed apex

    Periradicular

    rarefaction

    approximately 5x5 mm

    in size around the

    mature apex

    Diagnosis Previously initiated Symptomatic apical

    periodontitis

    Pulp necrosis

    Asymptomatic apical

    periodontitis

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    Treatment Course

    First appointment

    Second appointment

    First appointment

    Second appointment

    1 week

    22 days

    Case 1

    Case 2

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    First Appointment

    Case 1 Case 2

    Informed consent

    Anesthetized with 2% lidocaine

    (1:100,000 epinephrine) and RD

    isolation

    No bleeding observed in the

    root canal on removal of the

    temporary restoration

    Irrigation with 5.25% sodium

    hypochlorite and drying with

    paper points Methyline blue dye application

    to check for fractures but none

    detected under microscope

    Take working length radiograph

    Informed consent

    Anesthetized with 2% lidocaine

    (1:100,000 epinephrine) and RD

    isolation

    Access cavity preparation

    performed under a microscope

    Take working length radiograph

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    Case 1 Case 2

    Mechanical instrumentation by

    step-back technique and

    copious 5.25% sodium

    hypochlorite irrigation

    Canal cleaned and shaped to

    the radiographic apex

    Apical foramen enlarged to 0.6mm with #60 K-file

    Canal dried and medicated with

    a paste form calcium hydroxide

    to the root apex

    Temporized with Cavit

    Mechanical instrumentation by

    step-back technique and

    copious irrigation with 5.25%

    sodium hypochlorite and 17%

    EDTA

    Apical foramen enlarged to 0.6

    mm with #60 K-file Canal partially dried with paper

    points and dusted with

    ciprofloxacin powder with a mini

    amalgam carrier

    The powder carried down to theapex with a hand plugger

    Canal coated with the powder

    by using hand files

    Temporized with Cavit

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    Second Appointment

    Case 1 Case 2

    Asymptomatic: percussion (-),palpation (-)

    Anesthetized with 2% lidocaine

    (1:100,000 epinephrine) and RD

    isolation

    Calcium hydroxide completely

    removed with 5.25% sodium

    hypochlorite

    Canal irrigated with 17% EDTA

    for 1 minute and dried withpaper points

    Asymptomatic: percussion (-),palpation (-)

    Anesthetized with 3%

    mepivacaine and RD isolation

    Canal irrigated with 5.25%

    sodium hypochlorite

    Canal irrigated with 17% EDTA

    for 1 minute and dried with

    paper points

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    Case 1 Case 2

    Bleeding induced in the canal by

    passing #40 sterile K-file 3 mmbeyond the apex

    Collacote placed in the canal

    after dusted with ciprofloxacin

    powder

    MTA placed 2 mm below

    cementoenamel junction

    against Collacote

    Tooth restored with GI

    Bleeding induced in the canal by

    passing #30 sterile H-file 3 mmbeyond the apex

    Collacote placed in the canal

    MTA placed 4 mm below

    cementoenamel junction

    against Collacote

    Tooth restored with GI

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    Follow-up

    Case 1 Case 2

    2-week Asymptomatic

    Percussion (-), palpation (-),

    Cold test (-)

    1-month

    Asymptomatic

    Percussion (-), palpation (-)

    Decrease in size of

    radiolucency along the

    mesial side of the root 2-month

    Sensitive to cold drink

    Cold test (-)

    1-month Asymptomatic: percussion (-

    ), palpation (-)

    Reduction in size of

    periradicular radiolucency

    5-month

    Periapical radiolucency had

    almost disappeared

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    Case 1 Case 2

    1 year and 3 months

    Tooth restored by general

    dentist Further decrease in size of

    radiolucency

    Endo-Ice: normal response

    PD: WNL

    EPT: 79/80

    22-month

    Percussion (-), palpation (-)

    Endo-Ice: normal response

    EPT: 34/80

    PD: WNL

    Complete resolution of

    periapical radiolucency with

    thinning of the root canal at

    the apical one-third

    18-month

    Asymptomatic: percussion (-

    ), palpation (-) EPT (-)

    Cold test (-)

    Complete resolution of the

    periapical radioluceny with

    intact lamina dura and

    normal PDL space.

    Thinning of the root canal at

    the apical one-third (-)

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    Case 1

    Post-OP 1 month 15 months 22 months

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    Case 2

    Post-OP 1 month 5 months 18 months

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    DISCUSSION AND CONCLUSION

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    22

    Immature Teeth Mature Teeth

    Challenge 1:

    Stem/Progenitorcells

    More

    Greater regenerationpotential

    Less

    Less regeneration potentialdue to aging

    Challenge 2:Apical pathways

    Open apex allow morestem/progenitor cells to

    migrate into root canals

    Narrower apical pathways

    Challenge 3:Canal disinfection

    Less difficult Greater difficulty

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    SCAP: Stem cells of the

    apical papilla

    Presence in mature teethhas not been reported

    May participate in pulp

    regeneration

    Need to be stimulated to

    migrate into root canal

    space Haynesworth et 1992Seo et al, 2004

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    Immature Teeth Mature Teeth

    Challenge 1:

    Stem/Progenitorcells

    More

    Greater regenerationpotential

    Less

    Less regeneration potentialdue to aging

    Challenge 2:Apical pathways

    Open apex allow more

    stem/progenitor cells to

    migrate into root canals

    Narrower apical pathways

    Challenge 3:Canal disinfection

    Less difficult Greater difficulty

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    Clinical Protocols for Mature Teeth

    Challenge 1

    Necessity toinduce

    bleeding

    Challenge 2

    Proper apicalenlargement

    Challenge 3

    Sufficientdisinfection

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    Induced Bleeding

    Successful revascularization cases by using

    calcium hydroxide without induced bleedingChueh et al, 2009

    The presence of SCAP in immature teeth

    Failed regenerative procedures attributed to

    inability to evoke bleeding into the canalDing et al, 2009

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    600-fold increase in stem cell markers in canal

    blood compared with the level in systemic

    blood when bleeding was induced inimmature teeth

    Lovelace et al, 2011

    Bleeding induced by passing files beyond theapex thought to stimulate the migration of

    adult stem/progenitor cells into the root canal

    Evoked bleeding may be critical in pulprevascularization of mature necrotic teeth

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    Clinical Protocols for Mature Teeth

    Challenge 1

    Necessity toinduce

    bleeding

    Challenge 2

    Proper apicalenlargement

    Challenge 3

    Sufficientdisinfection

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    Critical Apical Size

    Revascularization can be accomplished inimmature teeth with the apical foramen

    greater than about 1 mm in diameter

    Pulp necrosis was observed in 87% ofautotransplanted premolars when the

    diameter of the apical foramen was smaller

    than 1.0 mm Andreasen et al 1990, Kling et al 1990, Cvek et al 1990

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    The apical foramen enlarged only up to 0.6

    mm in the present report Bleeding was not induced in tooth replantation

    studies

    Bleeding evoked to enhance the migration of

    stem/progenitor cells

    No clinical evidence yet with regard to the

    critical apical size in clinical regenerative

    endodontic treatment

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    Clinical Protocols for Mature Teeth

    Challenge 1

    Necessity toinduce

    bleeding

    Challenge 2

    Proper apicalenlargement

    Challenge 3

    Sufficientdisinfection

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    Canal Disinfection

    Mature teeth have more complex root canal

    anatomy than immature teeth

    Disinfection in immature necrotic teeth

    Chemical means: antimicrobial irrigation and

    intracanal medication

    Mechanical (-)

    Disinfection in mature necrotic teeth

    Chemical + Mechanical instrumentation

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    Effect of Chemical Agents

    Ca(OH)2

    Antibiotics

    Combination

    Cirpofloxacin

    EDTA

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    Calcium Hydroxide

    Did not kill human mesenchymal stem cells

    when concentration range between 0.01

    mg/ml~100 mg/mLRuparel et al, 2012

    Calcium hydroxide dressing in Case 1 but not in

    Case 2

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    Antibiotics

    4 different combination antibiotics including

    triple, double, and modified triple antibiotics

    and Augmentin showed detrimental effects on

    survival of the stem cells in all concentrations 1 mg/mL

    Ruparel et al, 2012

    Concentration of pastes used in regenerationsignificantly higher

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    Combination

    Triple antibiotics (metronidazole, ciprofloxacin

    and minocycline)

    Double antibiotics (metronidazole and

    ciprofloxacin)

    Eradicate bacteria isolated from infected

    dentin and pulp in vitro, although complete

    eradication not shown in vivo

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    Combination antibiotics could be more

    effective in immature teeth where no or

    minimal mechanical instrumentation is

    performed

    A combination of antibiotics may not beneeded in mature teeth ifthorough

    chemomechanical instrumentation is

    performed

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    Ciprofloxacin

    Broad-spectrum antibiotic against both gram-

    positive and gram negative bacteria

    Case 1: 7-day Ca(OH)2 dressing and Ciprofloxacin

    dusting after bleeding was evoked

    Case 2: Medicated with ciprofloxacin for 22 days

    Ciprofloxacin dusting procedure might be

    harmful for survival of migratedstem/progenitor cells

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    Concentration of ciprofloxacin used in the

    present report

    Dusted in the wet canal

    Did not show a thick paste-like or slurry-like

    consistency in the canal

    Not strong enough to kill the migrated cells

    Prevent the migrated cells from beingcontaminated by remaining bacteria

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    EDTA

    Suggested to be a single irrigant for pulp

    regeneration in immature necrotic teeth at

    the second appointment

    Promote SCAP survival (89% viability)

    Lower cell viability (74%) was observed when

    both sodium hypochlorite and EDTA were

    used

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    5.25% sodium hypochlorite and 17% EDTA

    used at the second appointment in both cases

    More thorough chemomechanicalinstrumentation required in mature necrotic teeth

    A significant decrease in viability of migrated cells

    was expected

    Final irrigation with EDTA may

    Stimulate the release of growth factors embedded in

    dentin matrix

    Enhance the odontogenic differentiation of migratedcells and angiogenesis

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    Cell Viability Suggested Use

    Ca(OH)2 0.01 mg/ml~100 mg/mL

    Combination

    ABX

    < 1 mg/mL, not necessary in mature teeth

    if thorough chemomechanical

    instrumentation is performed

    Cirpofloxacin < 1 mg/mL, promote almost 100% survivalof SCAP

    EDTA Final irrigation with EDTA

    NaOCl Necessary for more thoroughchemomechanical instrumentation

    required in mature necrotic teeth

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    Outcome Assessment

    Radiographic healing of apical periodontitisand clinical symptoms

    Case 1 and Case 2: complete resolution

    Positive response to pulp vitality test Case 1: EPT (+), cold test (+)

    Case 2: negative

    Thickening of root dentin Case 1: apical third, < immature teeth

    Case 2: not observe, longer f/u required

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    Case 1 Case 2

    Revacularization+ +

    Odontoblastic Layer + (?) -

    Innervation + -

    Other diagnostic tools to detect the presence

    of apical vital tissues in root canals may need

    to be developed for more accurate initial

    outcome assessment

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    Clinical Situations

    Immature teeth with irreversible pulpitis Filled with pulp-like loose connective tissues 3.5

    weeks after regenerative endodontic treatment on

    the basis of histologic observation Shimizu et al 2012

    Immature teeth pulp necrosis

    No histologic findings reported yet

    Mature teeth with pulp necrosis and apical

    periodontitis

    Cell transportation and cell homing might be

    needed

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    Thanks for your attention!

    Presenter: PGY1

    Date: 2013.07.30

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