ImmatureTeethWithPeriradicularPeriodontitisorAbscessUndergoingApexogen - PDF document

ImmatureTeethWithPeriradicularPeriodontitisorAbscessUndergoingApexogenesis:AParadigmShiftLing-HueyChueh,DDS,MS,*andGeorgeT.-J.Huang,DDS,MSD,DScFourclinicalcasesofimmatureteeththatdevelopedperiradicularperiodontitisorabscessunderwentaservativetreatmentapproach,i.e.withoutcanalin-strumentation.Instead,onlycopious2.5%NaOClirrigationwasperformed.Allcasespresentedhereindevelopedmatureapicesafter7monthsto5yearsaftertheinitialtreatmentwithoutcomplications,althoughnarrowingcanalspacewasobserved.Ourclinicalobservationssupportashiftingparadigmto- Fromthe*EliteDentalClinic,Taipei,Taiwan;andtheUniversityofMaryland,CollegeofDentalSurgery,Dental CaseReport/ClinicalTechniques JOE—Volume32,Number12,December2006ApexogenesisinImmatureTeethWithPeriradicularPeriodontitis/Abscess treatment,patientpresentedasymptomatic.HardbarrierwasdetectedafterremovalofCa(OH)paste.AnewmixtureofCa(OH)wasplacedandtheaccessclosedwithCaviton/IRM.Sevenmonthsafterthefirstvisit,thetoothremainedasymptomaticbutstillshowedanopenapexFig.2).Theperiapicalradiographmade11monthsaftertheinitialtreatment(Fig.2)demonstratedamorenarrowedrootcanalcom-paredtothatshowninFig.2.Therefore,theIRMandpartoftheCavitonwereremovedandreplacedwithamalgam.At20monthsaftertheinitialtreatment,theradiographicexaminationshowedhealingoftheperi-apicalboneandmorereductionoftherootcanalspace(Fig.2).At35monthsaftertheinitialtreatment,theradiographicexaminationrevealedamarkedreductionoftherootcanalspaceandmaturationoftherootapexFig.2Case2A10-year-oldAsianboycomplainedoftoothacheinthemandib-ularposteriorregion4daysbeforetheappointmentandtheconditiongraduallybecameworsewiththedevelopmentofswellingontherightcheek2daysbefore.Accordingtothepatient’sstatement,ice-packingwashelpfulinpainrelief.Thepatient’spastmedicalhistorywasunre-markable.Intraoralexaminationrevealedaswellingatthebuccalgin-givaandalveolarmucosabetweenteeth#28and#29andcentralcuspfractureoftooth#29(Fig.3).Tooth#29showedagradeImobility,anegativeresponsetocoldtestandasensitivitytopalpationandpercus-sion.Radiographicfindingsshowedimmaturerootwithopenapex.Extensiveradiolucencywasobservedintheperiradicularregionex-tendingcoronallyonthemesialaspectoftheroot(Fig.3).Theclinicaldiagnosiswaspulpnecrosiswithacuteperiradicularabscess.Withoutanesthesia,thetoothwasaccessed.Patientfeltmildpainuponreachingthepulpchamberandcopioushemorrhagewasnoted(Fig.3).Asperformedincase1,pulpchamberwasirrigatedwithNaOCl,dried,paste(Merck)placedintothepulpchamberandthecanal,andtheaccesssealedwithglass-ionomercement.Atthe4thweekaftertheinitialvisitandtreatment,thetoothwasasymptomaticandthesofttissuehadhealed.Hemorrhagefromthecanalwasobserveduponac-cessing.Thecanalwasagainirrigated,Ca(OH)placed,andtheaccesssealedasbefore.Periapicalradiographmadeafterthesecondtreatmentshowedpartiallyhealedperiradicularbonewithanopenapexoftooth#29(Fig.4).At8weeksthepatientreturnedasymptomatic.Afteraccessing,calcifiedbarrierwasdetectedbyprobingwithaperiodontalprobe.Ca(OH)wasrefreshedandthetoothsealed.At7monthsthepatientreturnedwithnosymptoms.Radiographicexaminationrevealednearlycompletematurationoftherootapexandhealingoftheperira-dicularboneexceptminorradiolucencyaroundtheapicalbone,likelytheresultofhealedbonewithlesstrabeculardensity.Therewasasignificantincreaseofhardtissuethicknessoftherootwithreducedcanalspace.Thecoronalthirdofthecanalappearedtobefilledwithcalcifiedtissue(Fig.4).ThetoothwasthensealedwithCaviton/Ketac-silver.Patientdidnotreturnforsubsequentfollow-ups.Case3A10-year-oldAsiangirlsufferedfromanacutetoothacheandwasreferredbyaprosthodontist.Theperiapicalradiographbroughtbythepatientshowedamesiallytiltedtooth#20withanopenapex(Fig.5Anemergencytreatment,formocresolpulpotomy,wasperformed9daysbeforeatthereferringclinic.Initialperiapicalradiographmadeaftertheemergencytreatmentrevealedaradiolucentlesion(mm)attheperiradicularareaoftooth#20withanopenapex(Fig.5Clinicaldiagnosiswaschronicperiradicularperiodontitisoftooth#20withpossiblepartialnecrosisofthepulp.Centralcuspfracturewassuspectedasthecauseofpulpinfection.Afteraccessing,nohemor-rhagewasobserved.Thecanalwasirrigatedwith2.5%NaOCl,medi-catedwithCa(OH)(Merck),andsealedwithIRM.Periapicalradiographtakenaftertheinitialtreatmentshowedanopen-apextooth#20witharadiolucentlesionattheperiradicularareaoftooth#20().Onemonthlater,theperiapicalradiographmadebeforetreatmentshowedacalcifiedbarrierinthemiddleportionoftherootcanal().Afirmmid-rootstopwasnotedbyprobing.FreshCa(OH) Figure1.Clinicalphotographandperiapicalradiographofcase1.,Photographshowingasinustractatthealveolarmucosabetweenteeth#20and#19andinsertionofagutta-perchapointintothesinustract(arrow).Thefracturedcentralcuspisevident.,Radiographshowingaradiolucentlesionattheperiapicalareaoftooth#20withawideopenapex.CaseReport/ClinicalTechniques ChuehandHuang—Volume32,Number12,December2006 placedandthetoothwastemporizedwithIRM.Anothermonthlaterandsubsequentlyevery2to3months,Ca(OH)wasrefreshedandaccesssealedwithCaviton/glass-ionomercement.Theperiapicalradiographmade4monthsaftertheinitialtreatmentshowedhealingoftheperia-picalbone(Fig.6)andthattaken10monthsaftertheinitialtreatmentdemonstratedagradualhard-tissuedepositiononthecanalwallandreductionofrootcanalspaceattheapicalhalfoftheroot(Fig.6Noendodonticprocedurewasmadeatthispoint(sixtreatments)onward.Atthe11thmonthaftertheinitialtreatment,patientcom-plainedofsensitivityofthetoothwhileundertakingorthodontictreat-ment.Periapicalradiographmadeatthattimeshowedamaturedapexoftooth#20withawell-formedlaminadura(Fig.7).Furtherhard-tissuedepositionofcanalwallandreductionoftherootcanalspaceattheapicalhalfoftherootwasobserved13.5monthsaftertheinitialtreatment(Fig.7).At18.5monthsaftertheinitialtreatment,therewasradiographicevidenceoffurtherdepositionofcalcifiedtissueattheapicalhalfoftherootcanal(Fig.7),thusthecoronalhalfoftherootcanalandthecoronalpulpchamberwerefilledwithamalgam().Atthe34thmonthaftertheinitialtreatment,thetoothwasasymp-tomaticwithcompleterootformationandanalmostcompletelycalci-fiedapicalhalfoftherootcanal(Fig.7).Fourandahalfyearsaftertheinitialtreatment,thetoothremainedasymptomaticbuttheapicalhalfoftherootcanalwascompletelycalcified(Fig.7Case4A9-year-oldAsianboyhadatoothachein#29for5daysandwentforanemergencytreatment,afterwhichthetoothwasleftopen.Pa-tient’smotherwastoldthatanendodontictreatmentwasneeded.Atthefirstendodonticappointment,periapicalradiographwasmadeandre-vealedanopenapexoftooth#29withoutnoticeableperiradicularra-diolucency(Fig.8).Thetooth,withoutspontaneouspain,wassensi-tivetopercussionandtheclinicaldiagnosiswaspulpnecrosiswithchronicperiradicularpathosis.Thepatientwasapprehensive,there-fore,thetestresultsmaynotreflecttheactualtissueresponse.Withoutanesthesia,therubberdamwasplacedandthecanalirrigatedwith40ml2.5%NaOCl.Noinstrumentationwasperformed,thecanalwasfilledwithCa(OH),andtheaccesssealedwithIRM.Twoweekslater,thesameprocedureswereperformed.Avisit5-weeksafterthefirstend-odontictreatment,thesameprocedureswereperformed,andafirmstopatmid-rootwasdetected.At5months,thesameprocedureswereperformed,andtheperiapicalradiographshowedprogressingapicalmaturationoftooth#29withanextensionoftherootlength(Fig.8At11,17,24(Fig.8),and32monthsaftertheinitialtreatment,sameprocedureswereperformedateachvisit.Threeyearsafterthefirsttreatment,rootformationwascomplete.Thecanalspacewasfilledwithamalgamtothepointofthecalcifiedbridge(Fig.8).At5yearsthere Figure2.Follow-upperiapicalradiographsofcase1.,Radiographmade7monthsaftertheinitialtreatmentshowinganasymptomatictooth#20withanopenapex.,Elevenmonthsaftertheinitialtreatmentdemonstratingaslightlynarrowedrootcanal.,Twentymonthsaftertheinitialtreatmentshowinghealingoftheperiapicalboneandmorereductionoftherootcanalspace.,Thirty-fivemonthsaftertheinitialtreatmentrevealingamarketreductionoftherootcanalspaceandmaturationoftherootapex.CaseReport/ClinicalTechniques JOE—Volume32,Number12,December2006ApexogenesisinImmatureTeethWithPeriradicularPeriodontitis/Abscess werenosymptoms,butevidenceofseverenarrowingofcanalspaceFig.8).Intraoralexaminationrevealedasoundtooth#29withoutdiscoloration(Fig.8Herewereportedfourclinicalcases,allofwhichhavebeencon-ventionallyconsideredasindicationsforapexificationtreatment.In-steadofutilizingendodonticfilestocleanandshapetheinfectedandpartiallyortotallynecroticpulp,thesecasesweretreatedwiththemostconservativeapproach,namelynoinstrumentationofthecanalbesidesirrigationwith2.5%NaOCl.Thetreatmentperiodsofthesecasesspanbetween1988and2000.Iwayaetal.()reportedanunconventionaltreatmentofanim-maturepermanenttooth(mandibular2premolar)withperiradicularabscessandasinustract.Thetoothwasinstrumentedbutnottoitsfulllengthbecausethepatientfelttheinsertionofasmoothbroach.InthefirstvisitthetoothwasleftopenandatthefollowingvisitsthecanalwasonlyirrigatedwithNaOClandhydrogenperoxidewithoutanyinstru-mentation.Antimicrobialagents(metronidazolandciprofloxacin)wereplacedinthecanalandatthenextvisitvitaltissuewasvisualized5mmapicaltothecanalorifice.Thirty-fivemonthslatertherootapexformationwascompletealongwiththickenedrootstructureastheresultofsignificantlyreducedcanalsizecomparedtotheadjacentnor-malfirstpremolar.Thetoothrespondedtoelectricalpulptest.Later,BanchsandTrope()reportedacaseofsimilarconditionbutwithmoreextensiveperiradicularboneloss.Theyappliedasimilartreat-mentprocedureexceptsomehemorrhagewasinducedtoallowbloodclotformationinthecanal.AremarkableresultcomparabletothereportbyIwayaetal.wasalsoachieved.Theyalsonotedthepositiveresponsetocoldtestattherecall.Inbothreports,theauthorsconsiderthattherewasaregainofvascularizationinthecanaltissue,possiblypulptissue.AlthoughIwayaetal.appliedCa(OH)atthe6thvisit,BanchsandTropeemphasizednottouseCa(OH)topreserveanyremainingviablepulptissueandHertwigepithelialrootsheath.Ourclinicalobservationssupportthisnotionasdemonstratedbycases3Figs.5)and4(Fig.8)inwhichplacementofCa(OH)fardownintocanalsmayhaveatleastpreventedthedepositionofhard-tissueforma-tioninthecoronalhalfofthecanals.Inthetraditionalapexificationtreatment,apicalbarrierisestab-lishedbytheformationofcementum-liketissueofvariousthicknesses. Figure3.Clinicalphotographsandperiapicalradiographofcase2.,Photographrevealingaswellingatthebuccalgingivaandalveolarmucosabetweenteeth#28and#29andcentralcuspfractureoftooth#29.,Radiographshowinganimmaturerootoftooth#29withanopenapexandanextensiveradiolucencyattheperiapicalandmesialregionsoftherootoftooth#29.,Photographdemonstratingcopioushemorrhageuponaccessingthepulpchamber.CaseReport/ClinicalTechniques ChuehandHuang—Volume32,Number12,December2006 ArecentreviewbyRafter()summarizesthehistologicalcharacteris-ticsreportedintheliterature.Thehardtissuebarrierhasbeende-scribedasacap,bridge,oringrownwedgethatmaybecomposedofcementum,dentin,bone,orso-calledosteodentinthatcandepositontheinnerwallsofthecanal(6–11).Cementumformationcanproceedfromtheperipheryoftheapextowardsthecenterindecreasingcon-centriccircles.Incontrasttoapexogenesis,apexificationtreatmentdoesnotgenerallyleadtoanadditionalformationofrootdentinoranextensionofrootlength.Theundesirableoutcomeisaweakrootsus-ceptibletofracture.Fillingthecanalfrommid-roottocoronalthirdwithresinbondingtostrengthentheroothasbeenadvocatedafterthecom-pletionofapexification().Conservativeapproachtoreserveanyremainingvitalpulptissuemayprovidehopeforabetteroutcome,althoughthecontrolofrootcanalinfectionmaybeadifficultissue.Thedurationoftheinfection,theinvolvedmicrobialspecies,thehostim-munity,andthesizeoftheopenapexallmaytheoreticallyplayaroleintheoutcomeofthisconservativetreatmentapproach.Inthepresentreport,withanutmostconservativeapproach,allcasesshowednoticeableapicalmaturationwithincreasedrootlengthbutasignificantnarrowingofcanalspace.Thequestionis,whetherthethickenedrootwasformedbypulptissuefromtheremainingvitalpulptissueattheapicalregionthatwasresistanttoinfection,capableofregeneratingthepulptissueinthecanalspaceandmakingnewdentin;orthethickenedrootwasformedbyperiodontalligament(PDL)tissue,whichgrewintotherootcanalfromtheapicalforamenanddepositedthecementumontotheinnersurfaceoftherootdentin.Althoughlackinghistologicaldatafromhumanspecimens,onemayspeculatebasedonanimalstudies.ReportsbyNevinsetal.(15,16usingrhesusmonkeysdemonstratedthataftertotalpulptissueremovalinimmatureteeth,eithertreatedwithCa(OH)orcollagengel,therewascementumtissueformationattheapexandinthecanal.PDL-liketissuecanalsobefoundincanaltreatedwithcollagengel.PDLandcementumtissuesformedinthecanalspacecanbeverifiedhistologi-callybythepresenceofSharpey’sfibers(Nevins,unpublisheddata).StudiesbyEllisetal.()andHitchcocketal.,()revealedthatwhenbloodsupplyiscutoffinthemiddleoftherootinmonkeys,thecanalspaceiseventuallyreplacedbycementumandPDLalongtheinnercanaldentinalwall,accompaniedbysomebonetissues.Thesetissuesmay Figure4.Periapicalradiographsofcase2.,Afterthesecondtreatmentshowingpartiallyhealedperiradicularboneandtooth#29withanopenapex.,Sevenmonthsaftertheinitialtreatmentshowingcompletematurationoftherootapex,healingoftheperiradicularbone,asignificantincreaseofthecalcifiedtissueintheroot,asignificantdecreaseofrootcanalspace,andthecalcifiedcoronalthirdoftherootcanal.CaseReport/ClinicalTechniques JOE—Volume32,Number12,December2006ApexogenesisinImmatureTeethWithPeriradicularPeriodontitis/Abscess extendintopulpchamber.Otheranimalstudiesfocusingonthechangesinpulptissueafterreplantationshowedthatvarioushardtis-suesincludingdentin,cementum,andbonemayforminpulpspacedependingonthelevelofpulprecovery(11,15,19–22).Therefore,ifoneassumesthetotallossofpulptissuebutremaininginasterilecondition,theoutcomeistheingrowthofperiodontaltissues.EvidenceofstemcellsinPDLhasrecentlybeenshownandtheformationofnewcementumischaracterizedbythepresenceofSharpey’sfibers(Thispossibilitymayexplaintheincreasedthicknessofthecanalwallandthesevereshrinkageofcanalspace.Thisdepositionofcementumorboneinthecanalmaygraduallyandeventuallyobliteratethespaceasdemonstratedinallfourcasespresentedinthepresentreportandthose Figure5.Periapicalradiographsofcase3.,Radiographbroughtbythepatientfromthereferringclinicshowingamesiallytiltedtooth#20withanopenapex.Radiographmadeaftertheformocresolpulpotomyrevealingaradiolucentlesionattheperiapicalareaoftooth#20withanopenapex. Figure6.Periapicalradiographsofcase3.,Radiographtakenrightaftertheinitialendodontictreatmentoftooth#20.,Radiographmadebeforethesecondtreatmentonemonthafterinitialtreatmentdemonstratingacalcifiedbarrierinthemiddleportionoftherootcanal.,Radiographmadebeforethefourthtreatment4monthsafterinitialtreatmentshowingahealingoftheperiapicalbone.,Radiographmadebeforethesixthtreatment10monthsafterinitialtreatmentdemonstratingagradualdepositionofcalcifiedstructureoftherootandreductionoftherootcanalspaceattheapicalhalfoftheroot.CaseReport/ClinicalTechniques ChuehandHuang—Volume32,Number12,December2006 reportedbyIwayaetal.()andBanchsandTrope().Tsukamoto-Tanakaetal.()observedhardtissueformationinratdentalpulpduringhealingprocessafterreplantation.Usinghistochemicalandim-munocytochemicalapproach,theyidentifiedspecificcellsandtheiractivitiesinthepulpandperiodontaltissues.Tertiarydentinformationwasobservedbynewlydifferentiatedodontoblasts,whereasosteoclastsassociatedwithbonematrixinpulpwereobservedincaseswheretertiarydentincouldnotberecognized.Thefateofhumanpulptissueafterdentaltraumashasbeenob-servedinclinicalradiographs.Andreasenetal.(25,26)andKlingetal.)showedexcellentradiographicimagesoftheingrowthofboneandPDL(nexttotheinnerdentinalwall)intothecanalspacewitharrestedrootformationafterreplantationofavulsedmaxillaryincisors.Somecasesdemonstratedpartialformationofrootaccompaniedwithin-growthofboneandPDLintothecanalspace.Intheirreports,whenteethcontinuedtodeveloprootstotheircompletion,normallyassoci- Figure7.Follow-upperiapicalradiographsofcase3afterthecompletionofsixtreatments.,Elevenmonthsaftertheinitialtreatmentshowingamatureapexoftooth#20withawell-formedlaminadura.,Thirteenandahalfmonthsaftertheinitialtreatmentdemonstratingfurtherdepositionofhardtissueintherootandreductionofcanalspaceattheapicalhalfoftheroot.,Beforeamalgamfilling18.5monthsaftertheinitialtreatmentexhibitingevidenceofdepositionofmorecalcifiedmaterialattheapicalhalfoftherootcanal.,Afteramalgamfilling18.5monthsaftertheinitialtreatment.,Thirty-fourmonthsaftertheinitialtreatmentshowingcompleterootformationandanalmostcompletelycalcifiedapicalhalfoftherootcanal.,Fifty-fourmonthsaftertheinitialtreatmentrevealingacompletelycalcifiedapicalhalfoftherootcanal.CaseReport/ClinicalTechniques JOE—Volume32,Number12,December2006ApexogenesisinImmatureTeethWithPeriradicularPeriodontitis/Abscess atedwithseverenarrowingofcanalspace,theauthorsconsideredpulpsurvivalafterthereplantation.Saad()reportedaclinicalcaseofamaxillaryincisorwithnonvitalpulpandwithperiradicularpathosisthatunderwentapexogen-esisaftercanalcleaningandshapingwithNaOClandinstrumentsandfilledwithCa(OH),althoughthecanalappearedobliteratedat2.5yearsafterthetreatment.LiebermanandTrowbridge()observedaclinicalcaseofapicalbridgeformationandwasabletoperformhisto-logicalexaminationsafterextraction.Althoughtheauthorsstatedthepresenceofatubulardentinandcementuminthecalcificbarrier,theirdatashowedthattheapicalbarrierisbasicallymadeofcementumthatnotonlyformsabridgebutalsoextendscoronallyalongthedentinalwall.Sharpey’sfibers,notmentionedbytheauthors,appeartoformbetweenthecanalcementumandthesofttissue.Takentogether,ifpulp Figure8.radiographsandclinicalphotographofcase4.,Radiographmadebeforethefirsttreatmentrevealinganopen-apexoftooth#29withoutnoticeableperiradicularradiolucency.,Fivemonthsaftertheinitialtreatmentshowingmoreapicalmaturationoftooth#29withanextensionoftherootlength.Twenty-fourmonthsaftertheinitialtreatmentexhibitinganearlycompleterootendformation.,Threeyearsafterthefirsttreatmentdemonstratingacompleterootformation.Therootcanalwasfilledwithamalgamtothepointofthecalcifiedbridge.,Fiveyearsafterthefirsttreatmentrevealingevidenceofseverenarrowingofthecanalspace.,Clinicalphotographtaken5yearsafterthefirsttreatmentshowingasoundtooth#29withoutdiscoloration.CaseReport/ClinicalTechniques ChuehandHuang—Volume32,Number12,December2006 tissueistotallylost,thecanalspacemaybeoccupiedbycementum,PDL,andbone.Inthissituation,itisdifficulttoidentifyclinicallyviaradiographsbecausethecanalspacemaywellbePDLtissueandthethickenedrootstructurebecementum.Ontheotherhand,iftherewassurvivedpulptissuedespitethedevelopmentofperiradicularabscessbecauseoftherichbloodsupplythroughthewideopenapex,apexogenesiscouldoccur.Eveninmatureteeth,theremayberemainingvitalpulptissueswhenaperiradicularlesionisdeveloped(29,30).Dentalpulpstemcellshavebeenidentifiedtoexistinpermanentteeth().Inthecaseofadevelopingtooth,thedentalpapillaattheapexmaycontainmorestemcellsthanamaturetoothandthereforepossessesagreaterpotentialtorebuildthelostpulptissueandcontinuetherootmaturation.Ifthisisthecase,usingrevas-cularizationtodescribethisphenomenondoesnotencompassthescopeofregenerationofpulptissueinwhichgenuinepulpcontainingfunctionalodontoblastsiscapableoflayingdownnewdentintocom-pletetherootdevelopment.Pulpstemcellsseededontoexistingdentinmaydifferentiateintoodontoblastsandmaydepositnewdentin(34,35Or,thesurvivedpulptissuefragmentsmayformdentininthecenterofthepulpandmixedwithingrowncementum(11,19).Inconclusion,whereasscientificallyitisinterestingtoknowthehistologicalfeatureofthetissuesinvolvedintheformationoftherootaftertreatment,clinicallyourcasereportsshownherealongwiththosebyothersstronglysuggestaparadigmshiftintheclinicalmanagementofthistypeofcases,i.e.provideafavorableconditiontoallownaturaltissueregenerationratherthanreplacementwithartificialmaterials.Furthermore,aconservativetreatmentformatureteethunderthiscircumstancemayevenbeapossibilityinthefuturewithadvancedtissueengineeringtechnologies).Bothbasicandclinicalresearchtowardreachingthisgoalis1.RafterM.Apexification:areview.DentTraumatol2005;21:1–8.2.GoldsteinS,Sedaghat-ZandiA,GreenbergM,FriedmanS.Apexification&apexogen-.NYStateDentJ1999;65:23–5.3.IwayaSI,IkawaM,KubotaM.Revascularizationofanimmaturepermanenttoothwithapicalperiodontitisandsinustract.DentTraumatol2001;17:185–7.4.BanchsF,TropeM.Revascularizationofimmaturepermanentteethwithapicalperiodontitis:newtreatmentprotocol?JEndod2004;30:196–200.5.WeislederR,BenitezCR.Maturogenesis:isitanewconcept?JEndod2003;29:776–8.6.GhoseLJ,BaghdadyVS,HikmatYM.Apexificationofimmatureapicesofpulplesspermanentanteriorteethwithcalciumhydroxide.JEndod1987;13:285–90.7.TorneckCD,SmithJS,GrindallP.Biologiceffectsofendodonticproceduresondevelopingincisorteeth.IV.Effectofdebridementproceduresandcalciumhydrox-ide-camphoratedparachlorophenolpasteinthetreatmentofexperimentallyin-ducedpulpandperiapicaldisease.OralSurgOralMedOralPathol1973;35:541–54.8.SteinerJC,VanHasselHJ.Experimentalrootapexificationinprimates.OralSurgOralMedOralPathol1971;31:409–15.9.WaliaT,ChawlaHS,GaubaK.Managementofwideopenapicesinnon-vitalperma-nentteethwithCa(OH)2paste.JClinPediatrDent2000;25:51–6.10.LiebermanJ,TrowbridgeH.Apicalclosureofnonvitalpermanentincisorteethwherenotreatmentwasperformed:casereport.JEndod1983;9:257–60.11.RitterAL,RitterAV,MurrahV,SigurdssonA,TropeM.PulprevascularizationofreplantedimmaturedogteethaftertreatmentwithminocyclineanddoxycyclineassessedbylaserDopplerflowmetry,radiography,andhistology.DentTraumatol2004;20:75–84.12.RabieG,TropeM,GarciaC,TronstadL.Strengtheningandrestorationofimmatureteethwithanacid-etchresintechnique.EndodDentTraumatol1985;1:246–56.13.PeneJR,NichollsJI,HarringtonGW.Evaluationoffiber-compositelaminateintheresto-rationofimmature,nonvitalmaxillarycentralincisors.JEndod2001;27:18–22.14.GoldbergF,KaplanA,RoitmanM,ManfreS,PiccaM.Reinforcingeffectofaresinglassionomerintherestorationofimmaturerootsinvitro.DentTraumatol2002;18:70–2.15.NevinsA,FinkelsteinF,LaportaR,BordenBG.Inductionofhardtissueintopulplessopen-apexteethusingcollagen-calciumphosphategel.JEndod1978;4:76–81.16.NevinsA,WrobelW,ValachovicR,FinkelsteinF.Hardtissueinductionintopulplessopen-apexteethusingcollagen-calciumphosphategel.JEndod1977;3:431–3.17.EllisE,3rd,CoxCF,HitchcockR,BakerJ.Vitalapicoectomyoftheteeth:a1–4weekhistopathologicalstudyinMacacamulatta.JOralPathol1985;14:718–32.18.HitchcockR,EllisE,3rd,CoxCF,Intentionalvitalroottransection:a52-weekhis-topathologicstudyinMacacamulatta.OralSurgOralMedOralPathol1985;60:2–14.19.NevinsAJ,FinkelsteinF,BordenBG,LaportaR.Revitalizationofpulplessopenapexteethinrhesusmonkeys,usingcollagen-calciumphosphategel.JEndod1976;2:159–65.20.SkoglundA,TronstadL.Pulpalchangesinreplantedandautotransplantedimmatureteethofdogs.JEndod1981;7:309–16.21.SheppardPR,BurichRL.Effectsofextra-oralexposureandmultipleavulsionsonrevascularizationofreimplantedteethindogs.JDentRes1980;59:140.22.KvinnslandI,HeyeraasKJ.Dentinandosteodentinmatrixformationinapicoecto-mizedreplantedincisorsincats.ActaOdontolScand1989;47:41–52.23.SeoBM,MiuraM,GronthosS,etal.Investigationofmultipotentpostnatalstemcellsfromhumanperiodontalligament.Lancet2004;364:149–55.24.Tsukamoto-TanakaH,IkegameM,TakagiR,HaradaH,OhshimaH.Histochemicalandimmunocytochemicalstudyofhardtissueformationindentalpulpduringthehealingprocessinratmolarsaftertoothrep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JOE—Volume32,Number12,December2006ApexogenesisinImmatureTeethWithPeriradicularPeriodontitis/Abscess