Faculty ofResearch Report
08/09Faculty of
Dentistry
Contents1 Foreword
2 FacultyResearchStrategy
3 StrategicResearchInitiatives
7 GraduateResearchProgrammes
8 GraduateCourseworkProgrammes
10 UndergraduateResearchOpportunitiesProgramme(UROP)
12 ResearchHighlights
17 CompletedResearchProjectsinFY2008/09
26 NewResearchProjectsAwardedforFundinginFY2008/09
33 ResearchCollaborations
34 ResearchAchievements
35 ResearchStatistics
Faculty of Dentistry Research Report 08/09
1Research Report 08/09Faculty of Dentistry
Researchvibrancyis integralforaninstitution’ssustainablegrowthanddevelopment.While thepast twoyearshavewitnessedinfrastructuralconsolidation,AcademicYear2008/09waswheneffortwasfocusedonemergingareasofresearchengagementandmulti-disciplinarycollaboration.
Thesettingupofastate-of-the-artFluorideLaboratoryaswellastheestablishmentofanOralBiofilmAnalysisfacilityincollaborationwiththeUniversityofOtago,undertheCraniofacialClinicalResearchUnit(CCRU)/DentalBiophotonics&BiomaterialsProgramme(DBBP)ResearchInitiativeswillfacilitatethestudyofadiversespectrumofbacteriaandyeasts,andpromisestobringtheFacultytoanotherintellectualparadigm.TheOralTissueRepositoryundertheCentreforCraniofacial&RegenerativeBiology(CCRB)hassupportedthemaidenstepsinthestudyofethicallylesscontroversial,dentalpulpstemcells,whichholdsupthepotentialofbridgingDentistrywithotherlife-sciencerelatedplatforms.
Thepursuitofacademicexcellencewouldonlybepossibleifexistingstrengthsarecapitalizedupon,coupledwithcontinualrecruitmentofglobalresearchtalent.TheFacultyhasprovidedanenginereadytobedriven,workinginconcerttocreateanincubatorthatwouldempowerustotakeontheincreasingresearchchallengesthatareemerging.
CitingArthurSchopenhauer“…thegreatestamountofknowledge,ifnot
elaboratedbyourownthoughts,isworthmuchlessthanafarsmaller
volumethathasbeenabundantlyandrepeatedlythoughtover.”.Excellence
isnotaboutcapacity,it’saboutmindpower.TheFaculty’sresearchenterprise
maybesmall,butifweperseverepositively,wecanmakeanimpact.
AssociateProfessorVarawanSae-LimViceDean(Research)
Foreword
Foreword
Faculty of Dentistry 2 Research Report 08/09
ToimproveOral,DentalandCraniofacialHealthandtheDeliveryofClinicalCare
Faculty Research Strategy
Faculty VisionTobeaDentalInstitutionofInternationalDistinction
Strategic Research Initiatives
Centre for Craniofacial Regenerative Biology (CCRB)
Dental Biophotonics and Biomaterials Programme (DBBP)
Faculty Mission
Research Mission
ToimproveOralHealththroughAcademicExcellence,HighImpactResearchandQualityClinicalService
Craniofacial Clinical Research Unit (CCRU)
Faculty Research Strategy
3Research Report 08/09Faculty of Dentistry
The Centre for Craniofacial and Regenerative Biology (CCRB)Contributed by Ag. Director Assoc Prof Yeo Jin Fei
Overview:Intheacademicsessionreviewed,besidesfacilitatingestablishedresearchprogrammeslikeembryonicstemcellresearchandorofacialpainresearch,CCRBispleasedtoreportthecompletionofthesetupofkeyinfrastructureandcapability,i.e.‘OralTissueDepository[OTR]’whichisessentialtonurturebuddingresearchthatharnessoraltissue-derivedadultstemcells.Withtheacquisitionofthiscapabilityofdentalpulpstemcell,CCRBaimstoadvancecell-basedresearchexploitableincraniofacialtissueregenerationandothertranslationalmedicalresearchentities.TheCCRB-OTRwillthereforepositiontheFoDintheresearchforefrontofthisglobalresearcharena.
Progress in FY 2008/09:TheOralTissueRepository,whichisestablishedasacoreresearchfacilityfollowingtheapprovalofInstitutionalReviewBoard,starteditsinitialoperationbysettingupallthebasicequipmentsandconsumablesrequiredfortissuecollectionandbanking.TheOTR–PatientInformationandConsentform,requiredfortheworkflow,wasrevisedandhadreceivedapprovalfromIRB.OtherOTRformsinclude:
1. OTRDataCollectionForm2. OTRLaboratoryInformationSheet3. OTRInterimsheet4. OTRParticipantContactinformationsheet
AbriefworkflowfortheoperationsofOTRwasintroducedstartingfromtakingpatient’sconsenttocollectionofspecimenfromtheNUHOperationTheatre.Asuccessfultrialrunwascompletedforthecollectionofafewspecimensi.e.thefirstthreetobecollected.Atpresent,OTRisfunctioningsuccessfullywithafewtoothspecimensinstore.Apilotstudyisbeingimplementedonisolationandcryopreservationofdentalpulpcellsfromhealthywisdomteeth.Infuture,weanticipatecollectingandcryopreservinggingivalandPeriodontalligamentcellsalongwithnon-wisdomtoothspecimens.Intheyearunderreview,CCRBhassecuredthreeAcademicResearchFund(AcRF)researchandonestart-upgrant(withatotalgrantamountofS$580,560)andanotherexternalcollaborationgrantwithSIMTechamountingtoS$88,7859.Dr.LiuHuaintheresearchteamunderAPCaoTongwon“TheChinaScholarshipCouncilAward”withaprizemoneyofUS$5000.APCaoTongtogetherwithProfessorYuGuang-yanofPekingUniversityPRCsecuredanInternationalCollaborationgrantamountforRMB2,570000fromtheMinistryofScienceandTechnology,PRC.CCRBthroughitsresearchteamsunderAPCaoTong&APYeoJinFeipublishedfourfull-lengthpapersinpremierjournals.
Strategic Research Initiatives
Faculty of Dentistry 4 Research Report 08/09
The Dental Biophotonics and Biomaterials Programme (DBBP)Contributed by Director: Assoc Prof Stephen Hsu
Overview:Progress in FY 2008/09:ThisyearthemembersofDBBPhaveobtainedtwoAcademicResearchFund(AcRF)research,onestart-upgrantandoneexternalgrant(withatotalofS$427,414.47),13articles(withninepublishedinthepremierjournals)andtworegionalresearchawards.Thethematicprogressissummarizedbelow:
Tooth-biofilm Interaction: • Dr.Anil’sgroupsuccessfullypublishedtwoarticlesinpremierjournals.Theteam
hasleveragedonthehighintensityfocusedultrasoundtodeliverantibacterialnanoparticlesintodentaltubules.OneUROPstudentteamutilizedtheLightActivatedDisinfection(LAD),withMBinemulsion(PF4),togeneratesinglet-oxygenfordestructionofbiofilmbacteria.Thestudentresearchteamwonanawardinthe2008IADR-SEAManilameetingandpublishedtheirarticleinareputablejournal.
• Anotherundergraduateresearchteam,supervisedbyA/PHsu,challengedthe“textbooktruth”anddemonstratedthecariostaticpotentialofanacidicdrinkcontainingsucrose,glucose,andlactobacillus(Yakult™,pH=3.65).Thisclinicaltrial,drivenbyacounter-intuitivehypothesis,wonthemtheBestPaperAwardinthe2008“GCAsia-SEAADEStudentPreventionProgramCompetition”.Theirresultshavepavedthewaytosecurearesearchgrantfurtheringtheirworktopreventwhitespotlesionsaroundorthodonticbrackets.
Laser-tissue interaction:• Dr.Anil’s teampublishedanarticleaugmentingantibacterialefficacyof
AdvancedNon-InvasiveLightActivateddisinfection,inadditiontotheirsuccessinmonitoringcompositionalchangesduringdentindemineralizationemployingElectronicImpedanceBasedSpectroscopy.
• A/PHsu’steaminvestigatedthe“maskingeffects”ofsalivaonlaser/heat-inducedphysicochemicalchangesinenamel,whichisacriticalissueforclinicallaserapplicationoncariesprevention.
Bio-imaging research: • A/PKelvinFoong’steamcontinuedbuilding3-Dstatisticalmodelstoprofiletooth
andhumanfaceusinglaserimagingmodalities,MRI,andconebeamCT.TheteampublishedtwoarticlesusingMRItoconductquantitativeanalysisonhumanmasticatorymuscles.
• A/PHsu’steamemployedthe2ndand3rdharmonicgenerationmicroscopyto characterize the crystalline lattice structures of pathological enamelhydroxyapatite.
Strategic Research Initiatives
5Research Report 08/09Faculty of Dentistry
The Dental Biophotonics and Biomaterials Programme (DBBP) cont’d
Biomaterial Research:• A/PKesonTan’sgrouppublishedthreepremierjournalarticlesinvestigating
osseointegrationandimplantstabilityusingfiniteelementanalysisandaneuralnetwork.Healsosecuredagrantinvestigatingthe3-Daccuracyofplastictransferimpressioncopingsforthreeimplantsystems.
• Dr.ClarisseNg launchedher start-upgrant to studybio-mimetic surfacemodification.
• A/PNgoutilizedhisstart-upgranttoworkonthemechanismsinvolvedintheremineralizationofpartiallydemineralizeddentineinthepresenceofglass-ionomer.
Strategic Research Initiatives
Craniofacial Clinical Research Unit (CCRU)Contributed by Director: Assoc Prof Jennifer Neo
Overview:Intheyearofreview,twoARFandtwostart-upgrants(totalingS$534,460)wereobtained.Fourarticleswerepublished,twoofwhichwereinpremierjournals.Theprogressissummarizedbelow:
Fluoride StudiesTheunitalsoestablishedastate-of-theartfluoridelaboratory(IonChromatography)whichwillbeusedtosupportprojectswhichincludethedetectionoffluorideinfluoridatedsalt,fluoridatedtoothpaste,fingernailsamplesandbabymilkformulae.
Caries Risk Assessment (CRA)A/PStephenHsu’sresearchteamhascarriedoutthefirstofitskindcommunity-basednation-widesurveytoassessthecariesriskamongpreschoolersinSingapore.Atotalof1,782preschoolerswererandomlyselectedfororalexamination,salivarytests,andquestionnairesurvey.ThestudyestablishedbiophysiologicalCRAmodelswhichcouldbeusefulforearlydetectionofcariesinchildrenandearlyinterventionwithcost-effectivecariespreventionprograminthecommunity.Intheclinic,itcanbeutilizedforevidence-baseddiagnosisandtreatmentplanning.
Studies in the pipeline include the following• Theimpactoforalhealthonthedailyperformanceofinstitutionalizedelderly
Singaporeans–apilotstudy• Evaluationofcariesriskassessmentmodelsamongindividualsundergoingmulti-
brackettherapy(fixedorthodonticappliance)• Identifyingriskofexacerbationofasymptomaticpersistentendodonticlesions
(APEL)andbuildingariskassessmentmodelforevidence-basedmanagement• Real-time computationmodels for determining the centreof resistance
forOrthodontics
Faculty of Dentistry 6 Research Report 08/09
Research Funding in FY 2008/09
Research Publication in AY 2008/09
$500,000
$400,000
$300,000
$200,000
$100,000
$0
C C R B D B B P C C R U
Research Units
Am
ou
nt
of
fun
din
g (
SGD
)
$427,414,47
14
12
10
8
6
4
2
0
C C R B D B B P C C R U
Research Units
No
. of
pap
ers
Premium
Leading
TotalReputable
Others
$338,629.42
0 0 00
$400,700 $400,700
Total
External Funding
NUS Funding
5
2 2
0
9 9
2
1
2 2
0 0
1
13
4
Strategic Research Initiatives
$88,785
7Research Report 08/09Faculty of Dentistry
List of Conferred MSc and PhD Students in AY 2008/09
Name Main Supervisor Degree Nationality Thesis Title
Annie Shrestha A/P Anil Kishen M.SC. Nepal Chairside Optical Sensor to Monitor Bacterial - Mediated Acidogenic - Profile of Saliva in Children
Md Nazrul Islam
Dr. Victor Fan M.SC. India Radiograhic assessment of bone regeneration in alveolar sockets with PLGA bioscaffold after teeth extraction
Shibi Mathew A/P Anil Kishen M.SC. Indian Enterococcus Faecalis Biofim Mediated Inflammatory Potential
Khoo Suan Phaik
A/P Adrian Yap PH.D. Malaysian Biopsychosocial characteristics as predictors of treatment outcome of TMD patients with symptoms of pain
Graduate Research Programmes
Faculty of Dentistry 8 Research Report 08/09
List of Conferred MDS Students in AY 2008/09
Endodontics
Student NameLim Siow HooiIntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Varawan Sae-Lim Dr. George YipCl A/P Chen Nah Nah
Research TitleIL-6 Expression Following Delayed ToothReplantation in a Canine Model
Student NameNg Yuk ChingIntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Varawan Sae-Lim Dr. George YipCl A/P Chen Nah Nah
Research TitleIL-8 Expression Following Delayed ToothReplantation in a Canine Model
OMS
Student NamePoh Hze-Khoong,EugeneIntakeAY2006/07
Main Supervisor/ Co-Sup(s)Dr. Khoo See MengAdj A/P Adrian YapDr. Chan Yiong HuakA/P Yeo Jin Fei
Research TitleA Clinical Prediction Rule for ObstructionSleep Apnea
Student NameWee Tze HaurIntakeAY2006/07
Main Supervisor/ Co-Sup(s)Dr. Poon Choy YokeA/P Yeo Jin Fei Dr. Andrew Tay
Research TitleNeurosensory Distrubance FollowingMandibular Setback Surgery Using BilateralSagittal Split Osteotomy: A Pilot Study of 10Patients
Student NameNorhisham Bin MohamedIntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Yeo Jin FeiDr. Aidan YeoDr. Chan Yiong Huak
Research TitleSurgical Complications Following MandibularThird Molar Removal: A ComparativeRetrospective study between the Young andMatured Population
Orthodontics
Student NameChan Feng Yi
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)Dr. Soh JenDr. Chew Ming TakDr. Chan Yiong HuakA/Prof Kelvin Foong
Research TitleOrthodontics and Quality of Health: A Patient-Centered Evaluation
Student NameChong Canon
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Kelvin FoongDr. Goh Poh SunA/P Ho Yew KeeA/P Ong Sim HengDr. Chan Yiong Huak
Research TitleComputed Tomographic Scanning of Plaster Models – A Study of Validity and Cost Benefit
Student NameLow Hwee Hiang
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)Prof Murray MeikleA/P Cao TongA/P Kelvin Foong
Research TitleThe development of a new in vitro model to study the effects of comprehensive mechanical strain on human periodontal ligament cells
Student NameKoh Poh Leong, Kelvin
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)Dr. Soh JenDr. Chan Yiong Huak A/P Kelvin Foong
Research TitleA Patient-Centred Perspective of Facial Profile Aesthetics
Graduate Coursework Programmes
9Research Report 08/09Faculty of Dentistry
List of Conferred MDS Students in AY 2008/09 (cont’d)
Periodontology
Student NameNg Cher Hui, Mervyn
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)Dr. Marianne OngA/P Lim Lum Peng Dr. Koh Chu GuanDr. Chan Yiong Huak
Research TitleTooth Loss & Patient Compliance in Periodontally Treated Patients: A Retrospective Analysis 7 Years or More AfterActive Periodontal Treatment
Student NameYap Kin Wai
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Lim Lum PengDr. Madeliene GunaratnamDr. Chan Yiong Huak
Research TitleSelf Reported Periodontal Disease and Periodontal Health Status in Adults in a Hospital and Private Practise Setting
Orthodontics
Student NameTan Ching Ching
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Kelvin FoongProf Toshio DeguchiDr. Chew Ming TakA/Prof Ong Sim HengDr. Chan Yiong Huak
Research TitleThree-Dimensional Smile Arc Analysis in Orthodontically Treated Class III Malocclusion Patients
Student NameWong Liping, Florence
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Kelvin FoongProf Toshio Deguchi Dr. Arthur LimDr. Chan Yiong Huak
Research TitleReliability of the 3dMDface Stereophotogrammetric System: Towards Developing an Industry Standard for Reliability Testing of Surface Imaging Devices
Prosthodontics
Student NameChan Wee Kiong
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Keson Tan Dr. Ansgar ChengDr. Wong Keng Mun
Research TitleInterface Fit Accuracy of 3 Implant-Conical Abutment Systems
Student NameLim Sze Kheng
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Hien Chi NgoA/P Keson Tan Dr. Anil Kishen
Research TitleAnti-Bacterial Property of An Electroplated Dental Casting Alloys
Student NameSee Toh Yoong Liang
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)A/P Keson TanCl A/P Chua Ee KiamDr. Quek Heng Chuan
Research TitleLoad Fatigue Performance Conical Implant Abutment Combinations
Student NameSng Hong Cheong, Jeffrey
IntakeAY2006/07
Main Supervisor/ Co-Sup(s)Prof Chew Chong LinCl A/P Chua Ee KiamDr. Teoh Khim Hean A/P Keson Tan
Research TitleBond Strength of Repaired Zirconium Ceramic Crowns
Graduate Coursework Programmes
Faculty of Dentistry 10 Research Report 08/09
Undergraduate Research Opportunities Programme (UROP)
Group No. : 07-01 Group No. : 07-02
Pain Reduction Following Third Molar Surgery with 830nm GaA1As Low Level Laser Therapy of Energy Densities 50 & 100 J/cm2
Group membersZhou Shicai, Chua Chew Kiat Simon Jude Chan Pei Yuan Song Yi Lin Luo Wenyuan
SupervisorsProf Loh Hong Sai A/P Yeo Jin Fei
3D Digitisation of Plaster models Using Computed Tomography- A Pilot Work on the Accuracy and Validation of the Approach
Group membersMelvin Liew Kang Ming Ng Jing Hao Hoo Swee TiangTan Jiunn Ming Gary Ode Wataru See-Toh Kai Mun
SupervisorsA/P Kelvin Foong A/P Keng Siong Beng
Group No. : 07-03 Group No. : 07-04
Advanced Non-invasive Light Activated Disinfection (ANILAD) : An alternative to caries removal by hand instrumentation for deep occlusal caries?
Group membersTan Hui Xian Melissa Cai Xingni Esther Ogawa Chong May May Gomes Mario Regino Wenliang SupervisorsA/P Anil Kishen A/P Jennifer Neo
A 3D Interactive and Visualisation Educational Platform in Oral Histopathology
Group membersZhuang Ronglin Lim Min Min Low Minhui Lu Zhiyin Yim Shao’en Joey Emilia Balasubramanian Suraj
SupervisorsA/P Yeo Jin FeiA/P Kelvin Foong A/P Keng Siong Beng
Group No. : 07-05 Group No. : 07-06
Cytotoxicity Testing of Hemostatic Agents, Bonewax and Surgicel, on CRL-1486 Cells
Group membersLeonardo Saigo Chew Qin’An Amelia Kwan Yi Alexia Chan Wai Seng Ong Guo An Sia Kia Suan Priscilla
SupervisorsA/P Cao TongA/P Yeo Jin Fei
Fibre Post : Does Fit or Different Post Space Cleaning Methods Affect Retention ?
Group membersTan Jun Da Joanne Ou Jiazhen Tang Hui Yun Marian Elizabeth Ho Swee Ferng Cindy Tan Wye Lynn Tan Hui Lu Shella
SupervisorDr. Lim Kian Chong
Undergraduate Research Opportunities Programme (UROP)
11Research Report 08/09Faculty of Dentistry
Faculty Research Day 2008
Undergraduate Research Opportunities Programme (UROP)
ThepurposeoftheUndergraduateResearchOpportunities Programme (UROP) was topromoteanddevelopresearchinterestineveryundergraduate student within the Faculty.Italsoenabledstudentsandfacultymemberstointeractsoastofostertiesinperformingtheresearchworkandprovidingtheopportunitytoacquireskillsfortheintellectualprocessofinquiry.Studentsworkedingroupsunderthesupervisionandguidanceofaresearchmentortoexploreresearchideasandtesthypotheses.
TheprogrammecommencedinYear2Term3andlastedforabout2years.Afinalresearchreporthastobesubmittedattheendoftheprogramme and selected groups will thenpresenttheirresearchfindingsduringtheFacultyResearchDay.FacultyResearchDay2008washeldon7Nov2008andatotalofsixgroupspresentedtheirfindingstoapanelofjudgescomprisingProfToshioDeguchi,ProfMurrayClydeMeikleandAssocProfStephenHsu.
The results of the competition were as follows:
StartingfromLeft:MrTokWeeWah,A/PKengSiongBeng,See-TohKaiMun,HooSweeTiang,TanJiunnMingGary,Ode
Wataru,NgJingHao,MelvinLiewKangMingandA/PKelvinFoong
StartingfromLeft:A/PJenniferNeo,CaiXingni,ChongMayMay,EstherOgawa,TanHuiXianMelissaandA/PAnilKishen
(Notinphoto:GomesMarioReginoWenliang)
StartingfromLeft:TanJunDa,JoanneOuJiazhen,TangHuiYunMarianElizabeth,TanHuiLuShella,HoSweeFerng
Cindy,TanWyeLynnandDr.LimKianChong
Winning Group - Group 2 (07-02)
Project Title3D Digitisation of Plaster models Using Computed Tomography-A Pilot Work on the Accuracy and Validation of the Approach
1st Runner Up - Group 3 (07-03)
Project TitleAdvanced Non-invasive Light Activated Disinfection (ANILAD) : An alternative to caries removal by hand instrumentation for deep occlusal caries?
2nd Runner Up - Group 6 (07-06)
Project TitleFibre Post : Does Fit or Different Post Space Cleaning Methods Affect Retention ?
Faculty of Dentistry 12 Research Report 08/09
Chairside Optical Sensor to Monitor Bacterial-Mediated Acidogenic-Profile of Saliva in Children
Research Highlights
Student: Dr.AnnieShresthaSupervisor: AssocProfAnilKishen
Despitemanyadvances indentistrytoday,areliable, costeffectiveand simple chairsidemethodtomonitorcariesactivityinanindividualisstill lacking.Themultifactorialetiologyofdental caries is considered to be the mainobstacleinthisdevelopment.Thecardinalstepincariesprocessistheformationofacidfollowingcarbohydrateintake,whichlowersthepHbelowthecriticallevel,resultinginthedissolutionanddisintegrationofdentalhardtissues.Further,certainsalivaryproteinsareknowntofacilitatebacterialadherenceandcolonizationto thetoothsurface.Thelevelsofsalivarytotal-proteinhavebeenassociatedwithbothcariesactivityandperiodontaldiseaseconditions.
Optical spectroscopy isahighlysensitivetechnique that can determine biochemicalparametersfromsalivabothquantitativelyandqualitatively. This studyaimed toapply theprinciplesofopticalspectroscopytomonitorbacterial-mediatedacidogenic-profileandtotal-proteinconcentrationofsaliva.Experimentswereconductedusingoptical spectroscopic
sensor (OSS) to monitor the bac ter ia l -mediatedacidogenic-profileof salivamixedwithsucrosefrom70childrenofagegroup6-12years.Bromophenolblue,apHsensitivephotoindicator,wasusedtomonitortherateofacidproductionbysalivarybacteriafollowingthe additionof sucrose. The findings fromtheOSSwerecomparedwiththepastcariesexperience(cariesscores:dmfsindex),cariesactivitydeterminedusingmutansstreptococcicounts(DentocultSM)andLactobacillicounts(DentocultLB)andpHshifts(pH-meter).TheOSS showed a decrease in the absorptionintensityat595nmwavelengthofsaliva-sucrosesamplewithdecreaseinthepH.Thehalf-lifedecayvaluedeterminedfromtheOSSdifferedsignificantlybetweenthecaries-active (CA),caries-inactive(CI)andcaries-free(CF)groups(P<0.05).ChildreninCFgroup(90%)showedlowMSandLBcounts.However,thiscorrelationwasweakincasesoftheCAandCIgroups.TheOSwasabletodistinguishchildrenshowingdifferentcariesactivity.
Figure 1:SchematicdiagramoftheexperimentalsetupoftheOSSusedinthestudy.
Abstract
MSc Project Thesis Title: Chairside Optical Sensor to Monitor Bacterial-Mediated Acidogenic-Profile of Saliva in Children Student: Dr Annie Shrestha Supervisor: Assoc Prof Anil Kishen Summary Despite many advances in dentistry today, a reliable, cost effective and simple chairside method to monitor caries activity in an individual is still lacking. The multifactorial etiology of dental caries is considered to be the main obstacle in this development. The cardinal step in caries process is the formation of acid following carbohydrate intake, which lowered the pH below the critical level, resulting in the dissolution and disintegration of dental hard tissues. Further, certain salivary proteins are known to facilitate bacterial adherence and colonization to the tooth surface. The levels of salivary total-protein have been associated with both caries activity and periodontal disease conditions.
Figure 1: Schematic diagram of the experimental setup of the OSS used in the study.
Optical spectroscopy is a highly sensitive technique that can determine biochemical parameters from saliva both quantitatively and qualitatively. This study aimed to apply the principles of optical spectroscopy to monitor bacterial-mediated acidogenic-profile and total-protein concentration of saliva. Experiments were conducted using optical spectroscopic sensor (OSS) to monitor the bacterial-mediated acidogenic-profile of saliva mixed with sucrose from 70 children of age group 6-12 years. Bromophenol blue, a pH sensitive photoindicator, was used to monitor the rate of acid production by salivary bacteria following the addition of sucrose. The findings from the OSS were compared with the past caries experience (caries scores: dmfs index), caries activity determined using mutans streptococci counts (Dentocult SM) and Lactobacilli counts (Dentocult LB) and pH shifts (pH-meter). The OSS showed a decrease in the
Computer
Spectrophotometer
Cuvette containing
saliva sample
Optical fiber
Light
source
MSc Project
Summary
13Research Report 08/09Faculty of Dentistry Research Highlights
Experimentswerealsoconductedtoquantifythetotal-proteinconcentrationofsalivausingOSS.AbsorptionIntensitiesforvariousproteinconcentrations were characterized using aproteinsensitiveindicatorcoomassiebrilliantblue(CBB).Finally,consideringtheabilityoftheOSStodetectmultipleparameters,afiberopticbasedsensorincorporatingtwosensingregionsfor pH (methyl red as the photosensitizer)andprotein(CBBasthephotosensitizer)wasfabricatedusingtheprinciplesoffiberopticevanescentwavespectroscopy(FOEWS)andsol-geltechnology.ThisexperimentdemonstratedtheabilityofFOEWStoquantifytotal-proteinconcentrationsandmonitor theacidogenic-profileofsalivausingasinglesensor.
This studyhighlighted theabilityofOSStodeterminebacterial-mediatedacidogenic-profileofsaliva,whichcanbeusedasacariesactivityindicator.TheFOEWSdevelopedwasabletomonitortheacidogenic-profileaswellasquantifythetotal-proteincontentofsaliva.TheOSScanbeasignificantapplicationforthechairsidemeasurementofclinicallyimportantparametersfromsaliva.
Figure 2:Graphsshowingdecrease
intheabsorptionintensity(595nm)of
salivaduetopHchangeasdetected
bytheOSS;(A)caries-active(CA);(B)
caries-inactive(CI)and(C)caries-free
(CF)groups.
Table 1: Differentparametersmeasuredfromchildrenofthethreecariesstatusgroups.Where,I0-opticalintensityattime
0;I180-opticalintensityattime180minandt1/2-half-lifedecayofthebacterialmediatedexponentialreaction.
1.2
1
0.8
0.6
0.4
0.2
0 6 0 1 2 0 1 8 0 2 4 0Time (minutes)
No
rmal
ized
inte
nsi
ty
(A)y = 0.9943e-0.0066x
R2 = 0.9578
(B)y= 1.1328e-0.0083x
R2 = 0.9578
(C)y = 0.9943e-0.0066x
R2 = 0.9876
BA C
Caries-Active (CA)
Caries-Inactive (CI)
Caries-Free (CF) Caries-Active (CA)
dmfs/ ds >1/ >1 >1/ 0 0/ 0 CA vs. CF CA vs. CI CI vs. CF
pH(T0-T180)
1.91±0.47 1.73±0.46 1.64±0.56 0.10 0.237 0.46
I0-I180 0.66±0.15 0.64±0.19 0.58±0.09 0.02* 0.77 0.40
Half life(t1/2)
94.92±57.49 66.88±62.53 136.72±46.30 0.005** 0.20 0.005**
Faculty of Dentistry 14 Research Report 08/09
Student: ProfKhooSuanPhaikSupervisor: AssocProf.AdrianYap&Dr.ChanYiongHuak
Introduction:TemporomandibularDisorders(TMD)encompassesacollectionofmedicalanddentalproblemsthatinvolvethemusclesofmastication,theTemporomandibularjointaswellasassociatedstructures.PainisthecommonreasonwhypatientswithTMDseektreatment.Thebiopsychosocialfactorsassociatedwithpainsymptoms(WIPS)inTMDpatientsandtheirroleinthepredictionofTMDtreatmentresponsearestilllargelyunknown.
Aims:Theaimsofthisprojectwereto(a)developacross-culturallyadaptedRDC/TMD(ResearchDiagnosticCriteriaforTMD)foruseinMalaysia,(b)comparethebiopsychosocialcharacteristicsofTMDpatientswithWIPSandwithoutpainsymptoms(WOPS)inamulti-racialurbanpopulationand(c)constructapredictivemodelforidentificationofnon-responderstoconservativeTMDtreatment.
Methods:TheRDC/TMDwascross-culturallyadaptedusingstandardproceduresandwasusedtocollectdataonthebiopsychosocialcharacteristicsof314TMDpatientsagedbetween18to74yearsfromanurbanMalaysiansetting.Across-sectionalstudycomparingthebiopsychosocialcharacteristicsofTMDpatientWIPSandWOPSwascarriedoutinordertodeterminefactorsthatwerelikelytobeassociatedWIPS.SelectioncriteriaforpatientsWIPSwasthepresenceofpainasthemainsymptom.PatientsWIPS(n=100)weregivenconservativeTMDtreatmentwithoutocclusalsplints.Patients’progresswasdocumentedat6weeksandat6months.OutcomemeasuresincludedimprovementinCPI(CharacteristicPainIntensity)andmaximalwidthofpain-freemouthopening.DataweresubjectedtounivariatefollowedbymultivariateanalysiswithSPSS.
Findings:Thecross-culturallyadaptedRDC/TMDwasfoundtobevalid,reliableandsuitableforuseinMalaysia.Differencesinsociodemography,physicalandself-reportedcharacteristicsandpsychologicalstatus
wereobservedbetween TMDpatientsWIPSandWOPS.Ofthese,factorsassociatedwithpainsymptomswerelimitedwidthofpain-freemouthopening(p=0.011),self-reportofnocturnaltoothgrinding/jawclenching(p=0.036),presenceofamyofascialpaindiagnosis(p=0.001)andlargerLRMF(limitationrelatedtomandibularfunctioning)scores(p=0.003).
Of the100TMDpatientsWIPSwhoreceivedconservativeTMDtreatment,69respondedpositivelywhile31didnot.Thesignificantfactorspredictiveofnon-responsetoconservativeTMDmanagementwerethefemalesex(p=0.013),limitedexcursive-protrusivejawmovement(p=0.014),highermusclepalpationscores(p=0.047),lowerdepressionscores(p=0.044)andself-reportsofuncomfortable/usualbite(p=0.014).
Amodelwasdevelopedforthepredictionofnon-responsetoconservativeTMDtreatment.Thiswasfoundtohaveasensitivityof80.6%,specificityof95.7%,negativepredictivevalueof91.7%andpositivepredictivevalueof89.3%.Respondershadgreaterimprovementinpsychologicaldistressscoresovertimewhencomparedtonon-responderstoconservativeTMDtreatment.
Conclusions:ThefindingsofthisstudyvalidatetheimportanceofbiopsychosocialfactorsinTMD.ThefoursignificantfactorsthatwereassociatedwithpainsymptomsinTMDpatientswerereflectiveofthepatients’self-reportedandphysicalcharacteristicswhilstthefivesignificantpredictivefactorsofnon-responsetoconservativeTMDtreatmentwerereflectiveofpatients’sociodemographic,psychologicalstatus,physicalandself-reportedcharacteristics.Potentialnon-responderstoconservativeTMDmanagementcanbeidentifiedbythesebiopsychosocialpredictorssothatamoretailoredtreatmentcanbeplannedfromtheoutset.ConservativeTMDtreatmentappearedtohavebeneficialeffectsonTMDpatientswithhighdepressionscores.
Biopsychosocial Characteristics as Predictors of Treatment Outcome of Temporomandibular Disorders (TMD) Patients with Symptoms of Pain
PhD Project
Research Highlights
15Research Report 08/09Faculty of Dentistry
Introduction:Ithasbeenwell-established that supportiveperiodontal therapy (SPT) is important inthemaintenanceoforalhealth. Therehasbeenincreasing emphasis on the use of “true”endpoints(e.g.toothloss)ratherthan“surrogate”endpointsfortheevaluationofeffectivenessofperiodontaltherapy.
Objectives:Theaimsofthisstudyweretoinvestigatetheincidenceand reasons for tooth lossduringactiveperiodontaltherapy(APT)andsupportiveperiodontaltherapy(SPT)inacohortofpatientstreatedinaninstitutionalpractice(NationalDentalCentreSingapore,NDCS).Comparisonwasmadewithasub-setofpatientswhofailedtoattendSPTfollowingAPT.PrognosticfactorsassociatedwithtoothlossduringtheSPTwerealsoidentified.
Subjects and Methods: This research comprised of two parts – alongitudinal retrospective cohort study (SPTgroup)andaclinicalrecallcross-sectionalstudy(non-compliance group). The longitudinalretrospectivecohortcomprisedofpatientswithchronicperiodontitistreatedandmaintainedforatleast7yearsbyperiodontistsattheDepartmentofRestorativeDentistry,NationalDentalCentreSingapore(NDCS).Patientswereidentifiedfromanelectronicpatientdatabaseandtheirrecordfolderswereretrievedandreviewed.Thenumberofteethpresentwasdeterminedatthreetimepoints:Initialexaminationandconsultation,endofAPTandthemostrecentSPTappointmentvisit.Reasonsandclinical/periodontalparametersfortoothlossweredocumented.Totalnumberoffoldersdrawnwas478anduponreview,273patientsmettheinclusioncriteria.
Thecross-sectionalcohortcomprisedofpatientswhodroppedoutaftercompletionofAPT(non-compliers).Theywereidentifiedfromthedatabaseandinvitedtoparticipateinthispartofthestudy.
Thepatientswererecalledandassessedontheexistingnumberofteethpresent.Afterreviewing1,318folders,207patientsmetthecriteriabutonly39patientsreturnedforclinicalassessment.
RelevantinformationwascollectedandenteredintoanExcelspreadsheet.DescriptivestatisticsweredoneusingSPSS.Thedifferencesinthetoothlossbetweenthe2groupswereanalyzedusing2 sample t-test if normality (assessedusingKomolgorovSmirnov)andhomogeneityassumptionsweresatisfiedotherwisethenon-parametric equivalentMannWhitneyU testwasapplied.Amultivariate linear regressionwasperformedtoadjustforrelevantcovariates.Significancewassetatp<0.05.
Results:ForthesubjectsintheSPTgroup,atotalof360teethwereextracted(1.3teeth/patient)duringAPT,withmulti-rootedteethhavingtwo-foldoddscomparedwithsingle-rootedteeth.DuringSPT(meanof10.7years),atotalof253teethwereextracted(0.9teeth/patient).Theannualtoothlossduetoperiodontitiswas0.03teeth/patient/year.Logisticregressionanalysisfoundthatageof>60wasahighlysignificantpredictoroftoothlossduringSPT(p=0.015),withadjustedoddsratioof2.1(95%CI:1.14–3.40).
Fornon-compliers(subjectswhofailedtoattendSPT),atotalof41teethwereextracted(1.1teeth/patient)duringAPT,whichwasnotsignificantlydifferentfromthoseonSPT.DuringdiscontinuationofSPTfor9.6years,atotalof107teethwerelost(2.7teeth/patient),a3-foldincreasecomparedwiththoseonSPT.Theannualtoothlossduetoperiodontitisinthenon-complierswas0.22teeth/patient/year,whichwas7-foldhigheroddsthanthoseintheSPTgroup(p<0.05).Logisticregressionanalysisfailedtoidentifytheage,gender,diabetes,initialperiodontaldiagnosisaspredictorsfortoothlossduringdiscontinuation.
Student: Dr.NgCherHui,MervynMain Supervisor: Dr.MarianneOngCo-Supervisors: AssocProfLimLumPeng,Dr.KohChuGuan&Dr.ChanYiongHuak
Tooth Loss & Patient Compliance in Periodontally Treated Patients: A Retrospective Analysis 7 Years or More After Active Periodontal Treatment
MDS Project
Research Highlights
Faculty of Dentistry 16 Research Report 08/09
Conclusions:Withinthelimitationsofthecurrentstudy,provisionofSPTledtominimaltoothloss,especiallyduetoperiodontitis,foraperiodof10yearsafterAPT.SPTisbeneficialregardlessofcompliance.However,completionofAPTwithoutSPTwillpredisposepatientstolosesignificantlymoreteethcomparedtopatientswhodoundergoSPT.
Research Highlights
17Research Report 08/09Faculty of Dentistry Completed Research
Projects in FY 2008/09
New Direction 1Aim:Todevelopa rapidandaccurate solution toconvertstoredorthodonticplastermodel fordigitalstorageusingconventionalhigh-resolutioncomputedtomographyasaviablesolutiontothecommonandexpensiveproblemofstorageforphysicalplastermodels.
Method: ApilotstudywasconductedononemaxillaryarchofaFrasacomodelofartificialhumanteeth.ThemodelwasscannedoncewiththeMinolta900VIVIDsurfacelaserscannerandthe64-sliceSiemensSomatomCTscanner.Mesio-distalwidthandbuccalcuspal-gingivalheightmeasurementsaremadeonbothvirtualimages.TheaccuracyisvalidatedagainstidenticalparameterstakenwithaCoordinateMeasuringMachine(CMM).Intheprecisionexperiment,thevirtualmodelsoftheCTandlaserscannerfromtheaccuracyexperimentareused.Theinter-caninedistanceismeasured10 times each on both virtual models. Themeasurementsarerepeated3dayslater.
Results:CTscanningoftheplastermodelisaccurateto0.39mmand0.80mmforbuccalcuspal-gingivalandmesio-distaldistances, respectively.Theprecisionerror iswithin0.2mmfortheinner-caninedistance.
Conclusion:TheconclusionfromthepilotstudyindicatedthatphysicalplastermodelscouldberapidlyandaccuratelyconvertedtodigitalproxiesusingCTscanning.
Afterthepilotstudy,anindepthstudyhassincestartedwiththeundergraduateUROPamdMDSOrthodonticresearchprogrammesto(i)identifytheoptimalCTscanningprotocolthatgivesthe
mostaccuratevisualdisplayofthevirtualmodel,and(ii)todeterminethecost-effectivenessofCTscanningincomparisonwithphysicalstorage.Anadditionalsteptodetermineaccuracyofmulti-sliceCTscannedplastermodelshadbeenundertakenusingconventionalCAD-CAMtechnology ingeneratingarapid-prototyped(RP)modeloftheCTscannedplastermodel.ThisRPmodelhasbeencomparedwiththeoriginalphysicalmodelusingCMM,andwillundergosurfacescanningforcomparisonofsurfacecontours.Datafromtheindepthaccuracy/precisionandcost-effectivenessstudieswillberepresentedattheUROPresearchpresentationinNovember2008andviaMDSthesisinJan2009.
New Direction 2Indevelopingtherapidandaccuratesolutiontothecommonandexpensiveproblemofstorageforphysicalplastermodels,theseconddirectionistodevelopa3DdigitalmethodofassessingtheIndexofOrthodonticTreatmentNeed(IOTN)andPeerAssessmentRating(PAR)indexstatusmalocclusionsfromuntreatedandtreatedcasesusingdigitalplastermodels.TheoutcomeofthisapproachwashighlypredictableasthecurrentresearchworkofthePIhasdevelopedtheabilitytodigitallyseparatetheindividualcrownsofeachtoothfromtheplastermodelbaseandgingival,andmovetheseparatedteeth.Theteamwasalsoabletodigitallyoccludethedigitalplastermodelsinmaximumintercuspationwithouttheaidofreferencebases.Withdigitallyoccludedmodels,thedigitalassessmentoftheseverityofthemalocclusionsviathePeerAssessmentRatingindexandtheIOTNcanbesemi-automated.Theseconddirection(startedinJanuary2008)wasstillworkinprogressunderaFacultyofEngineeringFinalYearProjecttodevelopthemeasurementsystemandGraphicalUserInterface(GUI)forthevirtualplastermodelsinocclusion.
Principal Investigator: AssocProfKelvinFoongTotal Project Value: S$66,705
An Assessment of Malocclusion Status in Hospital Based Orthodontic Patients
Summary/Achievements
Faculty of Dentistry 18 Research Report 08/09Completed Research
Projects in FY 2008/09
DemyelinationoftheperipheralnerveinvolveschangesintheUltrastructuresofmyelinandaffectssodiumandpotassiumchannelsatthenodesofRanvier.LowLevelLaserTherapy(LLLT)hasbeenpreviouslyreportedtopromotemyelination.Thisstudyusedchemicaldemyelinationachievedbylysolecithinapplicationontheexposedsciaticnerves. LLLTwasgiven to theexperimentalanimals.Therateandcompletionofremyelinationisnotedtogetherwiththereturnofnormalfeaturesofsodiumandpotassiumchannels.Inthecontrol
animals,demyelinationwasallowedtotakeitscourseandtherate&completionofremyelinationwereassessed.AcomparisonoftheresultsofthetwogroupsofratsdemonstratedasignificanteffectsoftheLLLTonremyelination.Theresultswerecommunicatedtotheinternationalmedicallasercommunity.Theimpactwouldbeseenintheclinicalmanagementofcurrentdemyelinationassociated neuropathic pain conditions likeTrigeminalneuralgia.
Principal Investigator: AssocProfYeoJinFeiTotal Project Value: S$45,150
The Effects of Low Level Laser Therapy on the Rat’s Sciatic Nerve, Following Lysolecithin – Induced Focal Demyelination
Summary/Achievements
Aimsi) Tofindouttheperiodontalhealthofacohort
ofadultdiabetesinSingaporeii) Toevaluate longitudinally theeffectsofa
periodontalhealthprogrammeonperiodontalhealthstatusandmetaboliccontrolaswellassomeinflammatorymarkersinadultdiabetics
Thesubjectsweredividedintothreeperiodontaltreatmentmodality:Scaling+oralhygiene,scalingandacontrol.Allsubjectswereexaminedatbaseline,3monthsand9months.At9monthsallgroupsreceivedscaling+oralhygiene.Clinicalexaminationswerecarriedoutusingstandardperiodontalparametersandbloodtestswerealsotakentoevaluatethemetaboliccontrol.
ResultsPatientswithgoodglycaemiccontrolpresentedwithlesssevereperiodontaldiseaseintermsof
%bleeding,%calculus,andsiteswithincreasedprobingdepths.
Therewasa significant improvementof theplaqueandbleedingscoresandprobingdepthsofallpatients.Improvementwasmostmarkedinthescaling+Oralhygienegroup.Improvementwascomparableinpatientswithacceptableandunacceptableglycaemiccontrol.
Improvementinperiodontalhealthdidnothavesignificantimpactonglycaemicandmetabolicserummarkers.
ConclusionThestudyhighlightedtherelevanceofperiodontaltherapyinimprovingperiodontalhealthofpatientswithdiabetes.
Principal Investigator: AssocProfLimLumPengTotal Project Value: S$114,125
Prospective Study of Periodontal Disease Risk Markers and Treatment Outcome of a Periodontal Programme for Adult Diabetics in Singapore
19Research Report 08/09Faculty of Dentistry
Demineralizationandresorptionofhardtissuesarecommonsignsofdiseaseprocesswhichoftenaremediatedbybacteria.Bacteriapossesstheabilitytosurviveharshenvironmentalandgrowthconditionsbygrowingasabiofilmandbacterialbiofilmhasbeenassociatedwithmanychronic infectionsdiseasesinhumanbeings.Whenbacteriagrowasbiofilmsonhardtissuesurfacessuchasenamelanddentine,underfavorableconditions,theyincreasetheacidityatthevicinityofthebiofilm/hard-tissueinterface.This localizedincreaseinaciditymayleadtohard-tissuedemineralizationandsubsequentdisintegration (resorption). Understandingthismechanismofbiofilm formationwould
facilitateustodevelopnon-invasivestrategies(a) to remineralize, thedemineralized-hard-tissuesand(b)topreventsubsequentbacteria-induced-demineralizationofremineralized-hard-tissues.Previousstudieshadhighlightedthatcollagenfibrilsundergochemicalmodificationduringbiofilmformationanddemineralization.In this study, in vitrodemineralization andre-mineralizationexperimentswasconductedonenamelanddentinemodelsusingbothpH-cycleModelandBacterialModel.Theroleofdifferentapproachestofunctionalizecollagenindemineralizedsubstrates(dentine),suchasdeprotonation,chelation,phosphorylation,etc,wereevaluated.
FigureSEMmicrographsofcross-sectionandlongitudinaldentinespecimensafterdifferentperiodsofdemineralization:
(a),2day;(b),4day;(c)and(d),6day;(e)and(f),10day;(g)and(h),14day;(i)and(j)control.Thespecimensin(d)and
(f)underwentsonicationtreatmenttoremovethebiofilm.Theinsertin(g)isaFSEMmicrographshowingnetworkof
collagenfibrils(arrow)onthesurfaceofintertubulardentine.Theinsertin(h)isamagnifiedimageoftheleftofthis
SEMmicrographshowingthebacterialcells(arrow)penetratingintodentinaltubules.ODT:orificeofdentinaltubuleDT:
dentinaltubule;ID:intertubulardentine;PD:peritubulardentine.
a b
c
g
e
h
i j
d
f
a b
c
g
e
h
i j
d
f
a b
c
g
e
h
i j
d
f
a b
c
g
e
h
i j
d
f
a b
c
g
e
h
i j
d
f
a b
c
g
e
h
i j
d
f
Completed Research Projects in FY 2008/09
Principal Investigator: AssocProfAnilKishenTotal Project Value: S$46,500
Biomimetic Remineralization of Demineralized Hard Tissue
Summary/Achievements
Faculty of Dentistry 20 Research Report 08/09Completed Research
Projects in FY 2008/09
Summary/AchievementsTheaimofthisstudywastocompareexvivoosteogenesisofhESCs-derivedosteogeniccellswiththatofhumansomaticosteoblasts;tocompareinvivoosteogenesisofhESCs-derivedosteogeniccellswiththatofhumansomaticosteoblasts.
The conducted study was to compare theosteogenic potential of human embryonicstem cells (hESCs) within two- and three-dimensional(2Dand3D)culturesystems.hESCsof theH1 line (Wicell Inc.,Madison,Wisc.,USA)wereinducedtoformembryoidbodies(EBs) through5daysof suspension culturewithinnon-adherentculturedishes.Followingenzymaticdissociation,theEBderivedsinglecellswereseededoneithernovel3DporousPLGAscaffoldsor2Dculturedisheswiththesametotalcellnumber.Osteogenicdifferentiationwasinducedthroughculturemediasupplementedwith dexamethasone, L-ascorbic acid andb-glycerophosphate.After3weeksofinvitroculture,quantitativeandqualitativeassaysofosteogenicdifferentiationwereconducted.Osteocalcinsecretionandalkalinephosphatase(AP)activitiesweredetectedatsignificantlyhigherlevelswithin3Dculturecomparedwiththe2Dsystem.Subsequently,thecell-scaffoldconstructswereimplantediniliaccrestdefectsofimmunosuppressedrabbits.After4weeks,theconstructsweresubsequentlyexplantedandcharacterizedbyhistologyandX-rayanalysis.
Formationofnewbonewasdetectedwithinandaroundtheimplantedscaffolds.Theresultsdemonstratethattheosteogenicdifferentiationofhumanembryonicstemcellsisenhancedina3Dculturesystemcomparedtoa2Dcultureenvironment.Upon implantation insitu,thedifferentiatinghumanembryonic stemcellscan contribute positively to the repair andregenerationofbonedefects.
ThisstudyalsoevaluatedPLGAscaffoldsforbone regeneration within a rabbit model.The scaffolds were implanted at two siteson thesameanimal,within theperiosteumandwithinbi-cortical bonedefectson theiliaccrest.Subsequently,theefficacyofboneregenerationwithintheimplantedscaffoldswasevaluatedat4,12and24weekspost-surgerythroughhistologicalanalysis.Inboththeintra-periosteumandiliacbonedefectmodels,theimplantedscaffoldsfacilitatednewbonetissueformationandmaturationoverthetimecourseof24weeks,eventhoughtherewasinitiallyobservedtobelittletissueingrowthwithinthescaffoldsat4weekspost-surgery.Hence,the3DprintedporousPLGAscaffoldsinvestigatedinthisstudydisplayedgoodbiocompatibilityandareosteoconductive inboth the intra-periosteumandiliacbonedefectmodels.
Theproject hasgenerated threepublishedpapersinpeer-reviewedinternationaljournals.
Principal Investigator: Dr.VictorFanCo-Principal Investigator:A/PTongCaoTotal Project Value: S$179,850
Characterization of osteogenesis by human embryonic stem cell derived osteogenic cells
21Research Report 08/09Faculty of Dentistry
Thesuccessofacastrestorationdependslargelyonadequate resistanceandretention form.Resistanceformisdefinedasthose‘featuresofatoothpreparationthatenhancethestabilityoftherestorationandresistdislodgementalonganaxisotherthanthepathofplacement’.Factorsthataffecttheresistanceofacrownincludeauxiliarypreparationfeatures, totalocclusalconvergence,occluso-cervical(OC)dimensionand luting cement.A recent reviewon theprinciplesoftoothpreparationproposedthat3mmbetheminimumOCheightforpremolarstopossessadequateresistanceform.Howeverthisnumberwasbasedontheoreticalcalculationsandmonotonicload-to-failurestudies.
Inmostcasesteeth inneedoffullcoveragerestorationshavelostsubstantialtoothstructure,thereby making it difficult to incorporateadequate resistance and retention form.Placementoffoundationrestorationshasbeenadvocatedtoreplacelosttoothstructurepriortocrownfabrication.Ifthetoothtoberestoredisseverelydamaged,thencrownlengtheningand /or or thodontic ex trusion must alsobeconsidered.
Inspiteofallthisinformationnostudieshavebeendonetodeterminewhetherthepresenceoffoundationrestorations(coresandpost-cores)canenhanceresistanceform.Mostofthestudiesoncoresfocusedontestingdifferentmaterials,whilethoseonpost-coresfocusedondifferentconfigurationsandferruleheightsrangingfrom0-2mm.
Theaimofthisstudywastoevaluatetheloadfatigueperformanceof teeth restoredwithpostsandcores,withvaryingtoothheights,andtocomparethemwithsimilargroupshavingnopostsandcores.Thesecondaryaimwastodeterminewhetheracriticaltoothheightexistedatwhichtheplacementofafoundationrestorationresultedinnosignificantdifferenceintheloadfatigueperformance.Threetestgroupswithpreparedtoothheightsof2,3and4mmweretested.Thesewerecomparedwithanotherthreegroupswithsimilartoothheights,thistimerestoredwithprefabricatedtitaniumpostsandcoreheightsof4,3and2mm,respectively.Castcompletecrownswere thenfabricatedandcementedwithzincphosphate.Afatigueloadof58.8Nwasappliedatanangleof135degreestothelongaxisofeachcrown-toothspecimen.Thenumberofcyclestopreliminaryfailurewasdetermined.Theresultsshowedthatforall3toothheights,groupswithfoundationrestorationshadsignificantlyhighernumberofcyclestopreliminaryfailurethanthosewithoutfoundationrestorations.
Thisin-vitrostudysuggeststhatplacementoffoundationrestorationsonteethwithshortferruleheightsimprovetheclinicalperformanceofthefinalrestorations.
Completed Research Projects in FY 2008/09
Principal Investigator: AssocProfJenniferNeoTotal Project Value: S$51,150
Effect of Foundation Restorations on the Load Fatigue Performance of Full Gold Crowns
Summary/Achievements
Faculty of Dentistry 22 Research Report 08/09
This project was conducted in two parts.The first partof the studywas carriedoutto obtain better insight into the causes ofpersistenceofEnterococcus faecalis in rootcanaltreatmentfailedteeth.ThisinvestigationwascarriedouttoexamineE. faecalisbiofilmmediatedinflammatoryresponse.ThreestrainsofE. faecalis(ATCC29212,OG1RFandFA2-2),grownasplanktonicandbiofilmweretestedfor(1)theirhydrophobicityandsurfacecharge(2) intracellular survival (3)ability to induceinflammatorymediators(TNF-α,IL-6andNO)productionbymonocytes,and(4)abilitytoco-aggregatewithActinomyces israeliitostimulateinflammatoryresponsesinmonocytes.Inthefirstphaseofthestudymonospeciesbiofilm/planktonicbacteria(E. faecalis)weretestedfortheir interactionwithTHP1cells (monocyte)and in-vitrodifferentiatedmacrophages. Inthesecondphaseofthestudy,adualspeciesbiofilm/coaggregation(E. faecalisstrainswithA. israelii)wassimilarlytested.Findingsfromthis studyshowedthatnutrient-deprivationcouldsignificantlyincreasethehydrophobicityandsurfacechargeofbiofilmcells.Inaddition,nutrient deprivation significantly increased(p<0.05)theintracellularviabilityofE. faecalis
cells internalizedbymonocytesand in-vitrodifferentiatedmacrophages.AmongthethreeE. faecalisstrainstested,OG1RFandATCC29212strainsexhibitedlongerdurationofsurvivalthanFA2-2strain.In-vitrodifferentiatedmonocyteswhenco-culturedwithplanktonicE. faecaliscellsexhibitedasignificantlyhigher(p<0.05)productionofTNF-α,IL-6andnitricoxidethanwithbiofilmcellsfromnutrient-richandnutrient-deprivedconditions.PlanktonicmonoculturesofA. israeliicellswereabletoinduceasignificantlyhigher (p<0.05)TNF-α, IL-6andnitricoxideproductionby themonocytes compared toA. israeliibiofilmcells.However,thesecretionofTNF-α,IL-6andnitricoxidedecreasedwhenmonocyteswereco-culturedwithA. israelii-E. faecaliscoaggregatesorasco-adheredbiofilm.Thisstudyshowsthatbacterialbiofilms,amodeofgrowth inharshenvironments similar topost-treatmentendodonticenvironment,couldpotentiateE. faecaliscellstosurvivewithinthehostimmunecellsandstimulateaninflammatoryresponse. In addition, coaggregation ofE. faecaliswithA. israelii,anotherendodonticpathogen,couldattenuatetheinflammatoryresponseandfacilitatetheintracellularsurvivalofbacteria.
Figure:THP1cells infectedwithE. faecalis
(ATCC29212)planktonicandbiofilmbacteria
.A&B THP1 cells infected with planktonic
bac ter ia. Arrow in f igure A shows the
internalized bacteria (green fluorescent).
C&Dshowsgreen fluorescingnutrient rich
biofilmbacteriawithinTHP1cellsandsurface
adheredbacteriaappearred.Arrowindicates
surfaceboundbacteria(redfluorescent).E&F
shownutrient-deprivedbiofilmcellswithin
theTHP1cells.Dataisrepresentativeofthree
independentexperiments.
A
D
B
E
C
F
Internalizedbacteria
Internalizedbacteria
Internalizedbacteria
InternalizedbacteriaInternalized
bacteria
Monocyte
Surfaceadheredbacteria
Completed Research Projects in FY 2008/09
Principal Investigator: AssocProfAnilKishenTotal Project Value: S$166,895
Intra-radicular Causes of Persistent Endodontic Infection
Summary/Achievements
23Research Report 08/09Faculty of Dentistry
AimsHigh-intensity focusedultrasound (HIFU)produces col lapsing cav itat ion bubbles.Thisstudyaimsto investigate theefficacyofcollapsingcavitationbubbles todeliverantibacterialnanoparticlesintodentinaltubulestoimproverootcanaldisinfection.
MethodsIn stage1,experimentswereperformed tocharacterizetheefficacyofcollapsingcavitationbubblestodelivertheminiatureplasterbeadsinto a tubular channel model. In stage 2,experimentswereconductedonroot-dentinblockstotesttheefficacyofHIFUappliedat27kHzfor2minutestodeliverantibacterialnanoparticlesintodentinaltubules.Afterthestage2experiment,thesamplesweresectionedandanalyzedusing fieldemission scanningelectron microscopy and energy dispersiveX-rayanalysis.
ResultsThestage1experimentshowedthatcollapsingcavitationbubblesusingHIFUdeliveredplasterbeadsalongtheentire lengthofthetubularchannel. Itwasobserved from the stage2experimentsthatthediffusionoffluidsalonewasnotabletodeliverantibacterialnanoparticlesintodentinaltubules.Thecollapsingcavitationbubbles treatment using HIFU resulted insignificantpenetrationup to1,000mmofantibacterialnanoparticles into thedentinaltubules.Thestatisticalanalysisshowedahighlysignificantdifferenceinthedepthofpenetrationofantibacterialnanoparticlesbetweenthetwogroups(<0.005).
ConclusionThecavitationbubblesproducedusingHIFUcanbeusedasapotentialmethodtodeliverantibacterialnanoparticles intothedentinaltubulestoenhancerootcanaldisinfection.(JournalofEndod2009;35:1028–1033)
Figure.FieldEmissionScanningElectronMicrographsof
dentinesamplefromcontrolgroupwithoutHIFUtreatment
(A-C).Thedentinaltubulesopeningtowardstherootcanal
wallisdevoidofanyantibacterial-nanoparticlesattached
tothesurface(A).Thecross-sectionofthedentinesamples
withexposeddentinaltubulesdoesnotshowantibacterial-
nanoparticleswithinthelumen(B,Cmagnifiedinletfrom
B).FieldEmissionScanningElectronMicrographsofdentinal
tubulesfromtheHIFUtreatmentgroupsample(D-F).Lower
magnificationviewofdentinaltubules(D).Theinletin
(D)ismagnifiedin(E)showingantibacterial-nanoparticles
penetratingintothedentinaltubules.Thedistributionof
antibacterial-nanoparticleswasfoundtobenon-uniform
alongthelumenofthedentinaltubules(blackarrow)and
thenanoparticlesshowedatendencytoformaggregates
(whitearrow).Asingledentinaltubulewithantibacterial-
nanoparticleswithinitslumen(F)showingaggregationof
antibacterial-nanoparticlesof100±20μmsizes.
A B
C D
E F
Completed Research Projects in FY 2008/09
Principal Investigator: AssocProfAnilKishenTotal Project Value: S$46,500
Removal of Bacterial Biofilms Using Focused Ultrasound for Endodontic Disinfection
Faculty of Dentistry 24 Research Report 08/09
Despitetheadvancesinoralhealthpromotion,dentalcariesremainsamainhealthproblemthreateningchildren’shealthworldwide. InSingapore,althoughperiodicoralhealthsurveyswereconductedamongschoolchildren, thecaries prevalence among preschoolers hasnotbeendocumented.Cariesriskassessment(CRA) isconsideredanessentialcomponentforcost-effectivecariescontrolandevidence-basedtreatmentplanning.Nevertheless,theapplicationof caries riskassessment in thecommunityandclinicalsettings ishamperedbythelackofapracticalcariesriskassessmenttoolwithsufficientsimplicityandaccuracy.ThemainobjectivesofthisstudyweretoprofilethecariesstatusofpreschoolersinSingaporeandtoestablishandvalidateanepidemiologicallyandclinicallypracticaltoolforcariesriskassessmentforcost-effectivecariescontrol.
With ethical approval andparents’writtenconsents, 1,782 children aged 3-5 yearswere recruited from 13 randomly selectedkindergartens.Thebaselinedatawereobtainedin 2005 through a parent-administeredquestionnaire,anoralexamination,andsalivarytests.After12months,thecariesstatusof1,576(88%)childrenwasfollowedup.TheplaquepHvaluesof1,207childrenweremeasuredthroughamicro-touchmethod. The cariesprevalenceandoralhealthknowledgeattitudesandpracticeweredescribedandcomparedamong ethnic and socioeconomic groups.Bothtraditionalstatisticalmethods(multipleregressions)andartificialneuralnetworks(ANN)wereemployedforconstructingandvalidatingcariesriskassessmentmodels.
This study revealed that dental caries is asevere oral health problem affecting 40%childrenaged3-5yearsinSingapore.Thecariesdistribution was highly skewed. Prominentoralhealthdisparityexistedamongethnicandsocioeconomicgroupsandwaspartlyexplainedbyamultilevelbehavioralpathwaysubstantiatedby Structural Equation Modeling. Multiplebiopsychosocialcariesriskfactors/indicatorswereidentified.Variouscariesriskassessmentmodelswereconstructedandvalidated.Withthe sensitivity/specificity of 82%/73% and90%/90%,thescreeningandfull-blownmodelsreachedahigheraccuracyincariesprediction,ascomparedwithCariogram.Thesemodels,cateringtovariousneedsatthecommunityandclinicalsettings,arepromisingtoolsforcost-effectivecariescontrolandevidence-basedtreatmentplanning.
The resultsof this studyhaselucidated thecurrentcariesprofileamongthepreschoolersinSingaporeandconfirmedtheresurgenceofcaries.ThehighaccuracyoftheCRAmodelsachievedinthisstudyhavewonaninternationalresearchawardconferredbytheInternationalAssociationforDentalResearch (IADR).Theresults have also drawn the attention ofgovernmentalagentsandhavebeenreviewedfortherelatedhealthcarepolicyplanning.
Completed Research Projects in FY 2008/09
Principal Investigator: AssocProfStephenHsuTotal Project Value: S$144,925
Caries Risk Assessment for Children in Singapore
Summary/Achievements
25Research Report 08/09Faculty of Dentistry New Research Projects Awarded
for Funding in FY 2008/09
Mechanicalstressisanimportantdeterminantofbonemassandarchitecture. Increases inbonestrainsaboveacertainthresholdhavea positive effect on bone mass, whereasreductionsinstrainmagnitudeleadtobonelossandosteopenia.Theaimofthisstudyistotestthehypothesisthatmechanicalstrainisakeydeterminantofosteoblastdifferentiationandfunction,andcanactoncellsoftheosteoblastlineageinadose-dependentmanner.Inotherwords, whether the osteoblastic responseresultsinanosteogenicorresorptivestimulusinboneisdependentuponthebiomechanicalenvironmentofthecells.
Specifically,mechanically-inducedstrainwillbeappliedtoratcalvarialosteoblastsinvitroinaFlexercellapparatusdesignedtodelivertensionorcompressionofvariabledurationtoculturedcellsundercontrolledexperimentalconditions.TotalRNAwillbeextractedfromthecells,assessedfordegradationstatusandthenassayedforthedifferentialexpressionofgenesinvolvedin(1)osteoblastdifferentiationandboneformation,(2)cell–cellandcell–matrixinteractions,and(3)apoptosis(programmedcell death). For genes showing significantdifferentialexpression,theculturesupernatantswillbeassayedforthecorrespondingproteinbyenzyme-linkedimmunosorbentassays(ELISAs),andtheirbiologicalactivitytestedusinginvitroboneresorptiveassays.
Theresearchincludes:
1. os teob las t pr imar y cu l ture: get t ingosteoblastsfromneonateSDrat’scalvarialboneandcharacterizingtheosteoblasts;
2. tests of osteoblasts’ functions undermechanicaltension:
(a) vitality of osteoblasts under the mechanical tensions:
(b) apoptosis of osteoblasts under the tension;
(c) biomolecular reactions of osteoblasts to mechanical tension: RNA extraction; RT-PCR microarrays; ELISAs analysis, etc;
3.results/statisticalanalysis;
Summary
Principal Investigator: Dr.LiXiaobingTotal Project Value: S$128,500
The Bio-molecular Responses of Rat-derived Osteoblasts to Mechanical Strain in vitro
Osteoblastprimarycultureandcharacterization:
1:primaryculture:16/02/2009----25/03/2009.
10neonatalSDratsused:calvarialbonescut,digested,
andplateout,andcellspassagedtoPassagefive(fig.1).
(fig.1):primarycalvarialderivedosteoblasts:P5;
Faculty of Dentistry 26 Research Report 08/09New Research Projects Awarded
for Funding in FY 2008/09
Dental implants requireaperiodof limitedor no loading in order for bone ingrowthandosseointegrationtoprogresssufficientlyfor the implant tobear load. Prematureorinadvertent loadingduring theperiodafterimplantationmayresultinlossoffixationwiththeformationoffibroustissueattheimplantbonejunction.Currentpracticeistolimitearlyloadbearingactivities,however,thismaynotbedesirablefromafunctionalorrehabilitativeperspective.Therefore,itishighlydesirabletoenhanceandacceleratebone ingrowthandosseointegration immediatelyafter surgery.This studyuseselectrospunnanofibersandbiomineralizationtomodifythetitaniumsurfacetoenhanceosseointegration.Ourhypothesisisthatthemodifiedsurfacewillimprovestemcellcaptureandthereforeincreasethenumberofosteoprogenitorcellsattheimplantsite.Ti6Al4Vdiscs were pretreated and PLGA, collagenblendedPLGA,nano-hydroxyapatite/PLGA,andnano-hydroxyapatite/collagen-blendedPLGAnanofiberswerefabricatedusingastandardelectrospinningprocess.Humanbonemarrowderivedmesenchymal stemcellswere thenseededontothetestsampleswithuntreatedtitaniumdiscasthecontrol.Thesampleswereincubatedfor10,20,30and60minutes,afterwhichtheattachmentefficiencyofeachsamplewasevaluated.At10minutes,cellsstartedtoadhere to all the modified surfaces. There
was50%ormorecelladhesiononthenano-hydroxyapatite/PLGA,andnano-hydroxyapatite/collagen-blended PLGA nanofibers at 30minutes.At60minutes,celladherencewas75%inthenano-hydroxyapatite/collagenblendedPLGA,64%inthenano-hydroxyapatite/PLGA,52%inthecollagenblendedPLGAand38%inthePLGAnanofibers.Nocelladhesionwasseenontheuntreatedtitaniumplatesat60minutes.Thissuggeststhatthesurfacemodificationsenhanceearlycellcapturewhencomparedtountreated titanium.Anano-hydroxyapatite/collagenblendedPLGAcoatedtitaniumsurfaceinparticular improves initialcellattachmentwhichmayprovetobebeneficialforenhancingosseointegration.
Electrospun nanofibers
Principal Investigator: Dr.ClarisseNgTotal Project Value: S$165,829.42
Biomimetic Surface Modification of Dental Implants for Enhanced Osseointegration
Summary
27Research Report 08/09Faculty of Dentistry
The aim of this study was to measure the3-Daccuracyofplastic transfer impressioncopingsof3implantsystems,asafunctionofimplantangulations.Thenewerplastictransferimpressioncopingshadnotbeentestedfortheiraccuracyintransferof implantpositiontoamastermodel.Errorsduringthisstageoffabricationofprosthesishadbeenshowntoleadtostressbuild-upintheimplantcomponentsand/orprosthesis.Non-parallelorangulatedimplantscouldleadpotentiallytoincreaseddimensionalinaccuracy.TheuseofaCoordinateMeasuringMachine(CMM)allowedthe3dimensionallydetection of these errors. This study wasintendedtocomparecomponentsfromthreeimplantsystems,vizTissueLevelImplantSystem
(Institut Strauman AG), Osseotite CertainSystem(ImplantInnovationsInc)andBranemarkImplantSystem(NobelBiocare).Mastermodelsusing twoadjacent implantswithdifferingangulationswillbefabricated.Astandardizedimpressionandmodel fabricationtechniquewouldbeusedtocreateworkingcasts.ThedifferenceinpositionoftheimplantsbetweenthemastermodelsandtheworkingcastsshallbemeasuredusingCMM.Quantificationofthesetransferinaccuraciesintermsoftheθx,θyandθzrotationaldisplacementsaswellasx,yandz lineardisplacements (6degreesoffreedom)wouldprovideclinicianswithrelevantinformationinassessingtheclinicalsuitabilityofthecomponentsandtechniquesstudied.
New Research Projects Awarded for Funding in FY 2008/09
Summary
Principal Investigator: AssocProfKesonTanTotal Project Value: S$50,880
3-D Accuracy of Plastic Transfer Impression Copings for 3 Implant Systems
Fig 2.CMMprobemeasurementtodefine3-Dpositionof
Implantabutments
Fig 1ImplantMasterModelwithPlasticPick-upImpression
Coping
Faculty of Dentistry 28 Research Report 08/09
Present study was carried out to examineglobalgeneexpression in thebrainstem, inamousemodeloforofacialpain.Mice thatreceivedfacialcarrageenaninjectionshowedincreasedmechanicalallodynia,whichpeakedat3-4daysafterfacialcarrageenaninjection,demonstratedbyincreasedresponsestovonFreyhairstimulationoftheface(Fig.1.).Themicebrainstemwereharvestedat3dayspost-injection,andanalyzedbyAffymetrixMouseGenomemicroarrays.CommongenesthatarechangedintherespectivesidesofthebrainstemwereidentifiedandclassifiedusingtheGeneOntology(GO)termenrichmentanalysisfromthe DAVID resource website (http://david.abcc.ncifcrf.gov/).Thetopcategoryshowed
“leukocy tes adhesion” and the 2 genesinvolved in this categoryareP-selectinandIcam-1.P-selectinandIcam-1expressionwerefurthervalidatedusingreal-timeRTPCRandwesternblot (Fig.2&3).WepostulatethatincreasedP-selectin and Icam-1expressioncould contribute to pro- rather than anti-nociception,probablythroughtheenhancementofmacrophage/monocyteentryintothebrain.Anattempttoreversefacialcarageenaninducedhyperalgesiausinginhibitorstothedifferentiallyexpressedgeneswill be carriedout. Thesecouldpavethewayforidentificationofnoveldrugtargetsfortheclinicaltreatmentofhumanorofacialpain.
UC
B
* *
*
*
* **
**
35
30
25
20
15
10
5
0
No
. of
Face
Str
oke
s
Left injected vs Left Untreated
BI 1D 2D 3D 4D 5D 6D 7D 8D 9D 10D 11D12D
UC
A
*
*
** *
**
**
35
30
25
20
15
10
5
0
No
. of
Face
Str
oke
s
Right injected vs Right Untreated
BI 1D 2D 3D 4D 5D 6D 7D 8D 9D 10D 11D12D
Fig. 1.ResponsestovonFreyhairstimulationofthefaceaftertissueinflammationinducedbycarrageenaninjection.
(A)Right-sidedfacialcarrageenaninjection.(B)Left-sidedfacialcarrageenaninjection.BI:beforeinjection,1Dto12D
referto1dayto12daysafterinjection.U:untreatedcontrol.C:afterfacialcarrageenaninjection.AnalyzedbyStudent’s
t-test.Asterisksindicatesignificantdifference(P<0.05).
New Research Projects Awarded for Funding in FY 2008/09
Principal Investigator: AssocProfYeoJinFeiTotal Project Value: S$146,400
Global Gene Expression Analysis in the Mouse Brainstem after Hyperalgesia Induced by Facial Carrageenan Injection
Summary
Day Day
29Research Report 08/09Faculty of Dentistry
Control
Control
P-selectin
Beta-selectin
A
UC
B
*
*30
25
20
15
10
5
0
Fold
Ch
ang
e
Right injected vs Right Untreated
ICAM-1 P-selectin
UC
A
*
*
30
25
20
15
10
5
0
Fold
Ch
ang
e
Left injected vs Left Untreated
ICAM-1 P-selectin
Fig. 2.Real-timeRT-PCRanalysisofdifferentiallyexpressedgenesinthebrainstemafterfacialcarrageenaninjection.
P-selectinandICAM-1inthemousebrainstemafterfacialcarrageenaninjection.(A)Right-sidedfacialcarrageenan
injection.B:left-sidedfacialcarrageenaninjection.U:untreatedcontrol.C:afterfacialcarrageenaninjection.Analyzed
byStudent’st-test.Asterisksindicatesignificantdifference(P<0.05).
Fig. 3.Westernblotanalysisofhomogenatesofthebrainstemforuntreatedand3-daypost-facialcarrageenan-injected
mice.(AandB)Leftpanels:theantibodytoP-selectin(A)andICAM-1(B)detectedsinglebandsat~140kDaand~90
kDa,respectively.Rightpanels:nobandsweredetectedinnegativecontrolsthatwereincubatedwithPselectinor
ICAM-1antigen-absorbedantibodies.
Treated
Treated
NegativeControl
NegativeControl
Icam-1
Beta-selectin B
A
New Research Projects Awarded for Funding in FY 2008/09
Faculty of Dentistry 30 Research Report 08/09
Tissue regenerated oral skin and mucosaequivalentshavebeensuggestedtobetheidealsubstitutestoreplacevariousautologousskinormucosalgraftsforthetreatmentofdefects,usuallybecauseofsurgicalexcisions,injuries,andcongenitaldiseasesintheoralmaxillofacialregion.Fortissueregenerationoforalskinormucosalgrafts,itcouldbepossibletoutilizeeitherEScellsderivedfromtheinnercellmassofblastocyst-stageembryos[Trounson,2002],oradultstemcellsofnon-epidermalorigin,suchasthatderivedfromthebonemarrow[Kataokaetal,2003]andperipheralbloodcirculation[KorblingM,etal,2002],whichhavealsobeenshowntobecapableoftrans-differentiationintothekeratinocytelineage.Nevertheless,therewereanumberoffactorsthatwouldnotfavortheuseofadultstemcells[NIH,2008a;Coraux,etal,2003;Green,etal,2003]overembryonicstemcells.Amongthem, themortalityandlimitedrenewalcapacityofadult stemcellswasmostambiguousandthesubjectofmuchcontroversy.Bycontrast,theimmortalityandself-renewal capacityofhumanembryonicstemcells(hESCs)wasunquestionable.Besides,hESCsaregeneticallyyoungerandhealthier.
TheresearchwastostimulateanddirectthehESCdifferentiationtowardsthekeratinocyte
New Research Projects Awarded for Funding in FY 2008/09
Principal Investigator: AssocProfCaoTongTotal Project Value: S$125,800
Keratinocyte Differentiation of hESCs for Potential Dental, Medical and Wide Biotech Needs
Summarylineages.hESCs-derivedkeratinocytesarethebestsourcetogeneratehumanoralskinandmucosa, which could be utilized for manypurposes.Themajorapplicationsarepotentiallyinthedental,medicalandbiotechareasof:(1)thestudyofgeneticanddevelopmentalmechanismsrelatingtoskinormucosaregeneration,(2)thestudyofgene/proteindeliverytherapytocureskinororalmucosalesions;(3)thestudyofcell-injectiontherapyforskinormucosarepair;(4)thestudyofcelltransplantation-basedskinormucosareconstructionandregeneration;(5)thediseasestudyanddrugdiscovery(NIH,2001)forskinandmucosa;(6)thedevelopmentofnoveltoxicityscreeningtestsforepithelium-relatedbiomaterialsanddrugs;and(7)thedevelopmentandvalidationofhESCepithelialmodelsforwide biosafety-health evaluation of foodproductsandsupplements,cosmetics,personalcareproducts,houseandofficeproducts,livingandworkingenvironment,water,soil,airandnaturalenvironment.ThekeratinocytelineagesderivedfromhESCswouldbeestablished inSingapore,asaresultofthisproject.Moreover,thescientificdataandintellectualpropertiesofhESCkeratinocytedifferentiationwouldbesetupinFOD/NUS,pioneeringinglobaldentistry,forvariousapplicationsinthenearfuture.
Human skin/mucosa cells differentiated from an embryonic
stem cell
Day
-21,
Hol
ocl
one
Day
-10,
K18
&D
api
Day
-20,
K14
&D
api
Day
-10,
K18
&D
api
CD
44
31Research Report 08/09Faculty of Dentistry
IntroductionTheformationofwhitespotlesions(WSL)aroundorthodonticbracketsisoneofthemajorrisksoffixedorthodontictreatmentandpresentsasanaestheticissuefororthodontistsandupto48%ofpatients.Severalstudieshavereportedthe increase inresistancetodemineralizationinenamelafterlaserirradiation.However,thelasereffectshavebeencharacterizedinchemicalmodelsbutnotinabiofilmmodelmimickingintra-oralconditions.Yakultisapopularsoftdrinkforchildrenandteenagersandhasdemonstratedacariostaticeffectinourpreviouspilotclinicaltrial.ThecombinedeffectoflaserandYakulthasnotbeeninvestigatedintheliterature.
Objective1)Tocharacterizeinabiofilmmodeltheeffectsofcarbondioxidelasertherapyonpreventionofenameldemineralizationaroundorthodonticbrackets;2)toevaluatetheeffectsofYakultonlasedenamelaroundtheorthodonticbracketsinthesamebiofilmmodel.
MethodsFor Phase-I: Freshly extracted premolar ormolarteethwithoutdecaywillbeselectedandorthodonticbracketswillbeplacedontheseteethwithaconventionalcompositeresin.Fourdefinedwindowareanexttothebracketswillbe irradiatedwith3setsof laserparameterswiththeremainingnon-irradiatedareaselected
asthecontrol.AbiofilmreactordevelopedbytheCenterforDiseaseControl(CDC,USA)willbeusedtodevelopadentalbiofilm,simulatingintraoralcondition and demineralization. Before andafter4-weekincubationwithoralbacteriaandpooledhumansaliva,themineralcontentoftheexperimentalandcontrolsiteswillbequantifiedbyaMicro-computedTomography(μCT)scanner.The factorial ANOVA will be employed tostatisticallyevaluatethepreventiveeffectsoflasertherapiesandthesite-specificityoflasereffect.ForPhase-II:Thesamelaserparameteremployedinthephase-IstudywillbeusedtopreventWSLaroundorthodonticbracketsinabiofilmsystemsuppliedwithdailyYakultrinsefor2weeks.Thesamemineralprofilingmethod(usingμCT)willbeconductedbeforeandafterthelesiondevelopmentinthesamebiofilmsystemplusadaily1-minflushofone-bottleYakultfortwoweeks.ThesampleswillberetrievedfromthesystemforenumerationofplaquepHattheendof2-weekand4-weekperiods.ThefactorialANOVAwillbeemployedtostatisticallyevaluatethepreventiveeffectsoflasertherapies,Yakult,andthesite-specificityonplaquepHandmineralloss.Theresultsofthisstudymaydeepenourknowledgeofpreventivelasereffectonenameldemineralizationinamicrobiologicalsystemandpavethewayfortheclinicalapplicationoflaserand/orprobiotictherapiesinpreventingwhitespotlesionsoforthodonticpatients.
Investigatingthebiofilmaroundthe
orthodonticbracketandlaser-induced
cariesprevention
TheCDCbiofilmreactor,developed
bytheCentersforDiseaseControl
andPrevention(CDC)In2002
MineralprofilingusingMicro-CTtoquantify
thecaries-preventiveeffectonenamel
Principal Investigator: AssocProfStephenHsuTotal Project Value: S$121,920
Effects of Yakult and laser therapy on preventing enamel demineralization around orthodontic brackets in a biofilm model
New Research Projects Awarded for Funding in FY 2008/09
Faculty of Dentistry 32 Research Report 08/09
Research Collaborations in AY 08/09
Research Achievements
Collaborating Organizations Year Department Region
Universities
Massachusetts General Hospital, Harvard University, USA 2007 - 2009 Restorative Department International
University of Texas Health Science Center at San Antonio, USA 2007 - 2009 Restorative Department International
University of Wisconsin Madison 2003 - 2009 Oral and Maxillofacial Surgery International
Harvard University 2004 - 2009 Oral and Maxillofacial Surgery International
Peking University 2007 - 2009 Oral and Maxillofacial Surgery International
Tsinghua University 2006 - 2009 Oral and Maxillofacial Surgery International
Zhejiang University 2005 - 2009 Oral and Maxillofacial Surgery International
University of Otaga 2009 Restorative Department International
Jiaotong University 2006 - 2009 Oral and Maxillofacial Surgery International
Industries
Bio-Scaffold 2004 - 2008 Oral and Maxillofacial Surgery Local
Research Institutes
SIMTech Pte Ltd, A*STAR 2007 - 2009 Oral and Maxillofacial Surgery Local
Tissue Modulation Laboratory 2007 - 2009 Preventive Dentistry Local
Research Awards & Prizes Awarded in AY 2008/09
Awardee(s) Name of Award International or Local/Regional
Awarding Agency
Title of Article/Project
A/P Cao Tong International Collaboration Grant, Ministry of Science and Technology, PRC
International Ministry of Science and Technology, PRC
Development of hESC models for toxicity evaluation
Dr. Liu HuaA/P Cao Tong (Supervisor)
The China Scholarship Council Award 2008
International China Scholarship Council
NA
33Research Report 08/09Faculty of Dentistry Research Achievements
List of Editorial Board Memberships in AY 2008/09
Name of Staff Name of Journal/ Book Series Journal Tier Position Held
Prof Loh Hong Sai Singapore Dental Journal Reputable Section Editor
Prof Murray Clyde Meikle
Royal College of Surgeons, Edinburgh. Journal
Reputable Editorial Board Member
A/P Anil Kishen Singapore Dental Journal Reputable Section Editor
Optics and Lasers In Engineering Leading Editorial Board Member
Journal of Applied Oral Science Others Editorial Board Member
Open Dentistry Journal Others Editorial Board Member
A/P Keng Siong Beng Singapore Dental Journal Reputable Editorial Reviewer
A/P Lim Lum Peng Singapore Dental Journal Reputable Editorial Reviewer
Oral Health & Preventive Dentistry Others Editorial Board Member
Hong Kong Dental Journal Others Editorial Adviser
A/P Neo Chiew Lian, Jennifer
Journal of Dentistry Premium Editorial Board Member
Operative Dentistry Others Editorial Board Member
A/P Ong Hui Lian, Grace European Journal of Dental Education Leading Board member
A/P Sae-Lim, Varawan Journal of Endodontics Premium Scientific Advisory Panel of Editorial Board
Journal of Periodontology Premium Reviewer
Dental Traumatology Premium Editorial Board Member
Journal Of Dental Research Premium Reviewer
Acta Biomaterialia Others Reviewer
Singapore Dental Journal Reputable Reviewer
A/P Tan Beng Choon, Keson
Journal Of Oral Rehabilitation Leading Editorial Board Member
Singapore Dental Journal Reputable Editorial Reviewer
A/P Yeo Jin Fei Singapore Dental Journal Reputable Editorial Reviewer
Dr. Clarisse Ng Chai Hoon
Journal of Prosthodontics Leading Editorial Board Member
Dr. Uy Joanne Ngo Singapore Dental Journal Reputable Editorial Review Board Member
Singapore Dental Journal Reputable Editorial Reviewer
Faculty of Dentistry 34 Research Report 08/09 Research Statistics
New Research Students by Nationality
Enrolment of Research Students35
30
25
20
15
10
5
0
12
11
10
9
8
7
6
5
4
3
2
1
0
AY 2001/02
AY 2001/02
AY 2002/03
AY 2002/03
AY 2003/04
AY 2003/04
AY 2004/05
AY 2004/05
AY 2005/06
AY 2005/06
AY 2006/07
AY 2006/07
AY 2007/08
AY 2007/08
AY 2008/09
AY 2008/09
Academic Year
Academic Year
No
. of
Stu
den
tsN
o. o
f St
ud
ents
PhD
Foreign Students (FS)
MSc
Singapore Permanent Resident (SPR)
2
7
13
17
1213
14
17 17
17
17
15
19
14 14
11
7 8 5
5
8
2 64
3
1
4
2
1
2
4
0
35Research Report 08/09Faculty of Dentistry
Research Fundings
New and On-going Research Projects
Research Statistics
$1,600,000
$1,400,000
$1,200,000
$1,000,000
$800,000
$600,000
$400,000
$200,000
$0
40
35
30
25
20
15
10
5
0
AY 2001/02
AY 2001/02
AY 2002/03
AY 2002/03
AY 2003/04
AY 2003/04
AY 2004/05
AY 2004/05
AY 2005/06
AY 2005/06
AY 2006/07
AY 2006/07
AY 2007/08
AY 2007/08
AY 2008/09
AY 2008/09
Financial Year
Academic Year
Am
ou
nt
of
Fun
din
gN
o. o
f St
ud
ents
On-going Projects
New Projects
22
30
22 23
20
22
15
14
7 68 8 8
5 5
8
$799,915
$217,000
$0
$550,000
$786,805
$393,300
$1,308,020
$1,009,346
$426,276
$0
$530,000$498,524
$20,000
$962,690
$528,550
$674,252$589,000
$260,647
$10,000
$818,207
$376,050
$95,000
$525,069
$592,000
NUS Funding
External Funding
Research Scholarship
Faculty of Dentistry 36 Research Report 08/09
Research Publications80
70
60
50
40
30
20
10
0FY 2001/02 FY 2002/03 FY 2003/04 FY 2004/05 FY 2005/06 FY 2006/07 FY 2007/08 FY 2008/09
Financial Year
Academic Year
No
. of
Pub
licat
ion
sN
o. o
f Pa
per
s
15
57
22
33
6
0
8 8
24
39
11
17
41
19
10
24
7
13
66 57
41
7369
47
29 28
Conference Papers120
100
80
60
40
20
0AY 2001/02 AY 2002/03 AY 2003/04 AY 2004/05 AY 2005/06 AY 2006/07 AY 2007/08 AY 2008/09
Total
4247
33
74
84
68
106
61
Research Statistics
Premium
Leading
TotalReputable
Others
1216
1 3 14
16
23
38
34
37Research Report 08/09Faculty of Dentistry
Research InternshipsTheFacultyofDentistryhasreceivednumerousstudentsfromvariousschools,bothlocallyandinternationallyasresearchinterns.TheseschoolsincludeJuniorColleges,Polytechnics,andoverseasUniversities.Thedurationoftheinternshipvariesfromafewmonthstoaboutayear.Theinternshipcaneitherbefull-timeorpart-time.
ThesestudentsreceiveguidancefromtheacademicstaffmembersfromtheFaculty,bylearningandworkingunderthespecificresearchprojectsofthestaffmembers.
Research Statistics
FACULTY OF DENTISTRYNational University of Singapore
5LowerKentRidgeRoad,Singapore119074Telephone:(65)67724987Facsimile :(65)67785742http://www.dentistry.nus.edu.sg