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SNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperContaminationoftitaniumdentalimplants:anarrativereviewJagjitSinghDhaliwal1·ShebaRaniNakkaDavid1·NurulRamizahZulhilmi1·SachinjeetKaurSodhiDhaliwal1·JoeKnights1·RubensFerreiradeAlbuquerqueJunior2Received:13November2019/Accepted:22April2020TheAuthor(s)2020OPENAbstractContaminationoftitaniumdentalimplantsmayleadtoimplantfailure.
Therearetwomajortypesofcontaminants:theinorganicandorganiccontaminants.
Theinorganiccontaminantsmostlyconsistofelementssuchascalcium,phos-phorus,chlorine,sulphur,sodium,silicon,fluorineandsomeorganiccarbons.
Whereasorganiccontaminantsconsistofhydrocarbon,carboxylates,saltsoforganicacids,nitrogenfromammoniumandbacterialcells/byproducts.
Contami-nantscanalterthesurfaceenergy,chemicalpurity,thicknessandcompositionoftheoxidelayer,however,welackclini-calevidencethatcontaminationshaveanyeffectatall.
However,surfacecleanlinessseemstobeessentialforimplantosseointegration.
Thesecontaminantsmaycausedentalimplantstofailinitsfunctiontorestoremissingteethandalsocauseafinancialburdentothepatientandthehealthcareservicestoinvestindecontaminationmethods.
Therefore,itisimportanttodiscusstheaetiologyofdentalimplantfailures.
Inthisnarrativereview,wediscusstwomajortypesofcontaminants:theinorganicandorganiccontaminantsincludingbacterialcontaminants.
ThisreviewalsoaimstodiscussthepotentialeffectofcontaminationonTidentalimplants.
KeywordsDentalimplant·Contamination·Prognosis·Titanium1IntroductionDentalimplantscangetcontaminatedduetotheecologi-calsystemintheoralcavitywithabundantmicroorgan-isms[1].
Commonelementalcontaminationfromorganiccarbonandtracesofelementsincludingoxygen(O),nitrogen(N),calcium(Ca)andphosphorus(P)foundondentalimplantsurfacesarepotentiallylinkedtofailureinre-osseointegrationwhenpartsofanimplanthadlostitsosseointegration[2].
Ithasbeenshownre-osseointegra-tionoccurswhenthereisaformationofadirectstructuralandfunctionalunionbetweenanimplantandbone,ithasbeenshownthatproperlycleanedimplantsindeedmayre-osseointegrate[3].
Henceseveralfactorssuchassurfacetopography,chemicalpurity,thicknessandcompositionoftheoxidelayer,surfacecleanliness,andtheexistenceofmetallicandnon-metalliccompoundsonthesurfaceseemstoinfluencethesuccessofimplantosseointegra-tion[4].
Currently,agrowingamountofevidence[5,6]sug-geststhattheimplantsurfacetopographyandchemistryhasgreatinfluenceontheosseointegrationprocessbyaffectingproteinsignallingandcellmigrationordiffer-entiation.
Bone-implantcontactarea,mechanicalinter-lockingandstressdistributionarerecognisablybetterinsurfaceswithacertaindegreeofroughnessincomparisontosmoothones,favouringosteoblast-likecellcolonisa-tion[7].
However,ithasalsobeenshownthatroughenedsurfacesenhancetheaccumulationofcontaminants[8].
Nevertheless,themechanismsbywhichinorganicandorganiccontaminantsinteractwiththeimplantsurfacesremainundefined.
Althoughmanymethodsofimplant*JagjitSinghDhaliwal,jagjit.
dhaliwal@ubd.
edu.
bn|1PengiranAnakPuteriRashidahSa'adatulBolkiahInstituteofHealthSciences,UniversitiBruneiDarussalam,JalanTungkuLink,Gadong,BruneiDarussalam.
2DepartamentodeMateriaisDentáriosEPrótese,FaculdadedeOdontologiadeRibeiroPreto,UniversidadedeSoPaulo,SoPaulo,Brazil.
ReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4decontaminationhavebeenattempted,noneofthemhavesucceededinproducingpredictableresults.
Implantsurfacedecontaminationremainschallengingandthusthedevelopmentofnew,effectivemethodsisnecessary[9,10].
Topographicalmodificationisfrequentlyadoptedintitanium-basedimplantstoproducethedesiredsurfacepropertiesbyusingdifferentsurfacetreatmentssur-facetreatmentssuchassandblasting,chemicaletching,anodization,lasertreatment,andsurfacecoatings[11].
Althoughthesesurfacetreatmentscanchangetheprop-ertiesoftheimplantsurfacesandonrareoccasions,mayalsoleadtoundesiredpropertiesandhence,contamina-tionoftheimplantsurfaces.
Humanbodyfluidscontaintraceelementssuchaschlorineandfluorideionswhereasourbonecompriseofcollagen,hydroxyapatite(Ca10(PO4)6(OH)2),andsomeani-onicandcationicsubstituentssuchascarbonates(H2CO3),sodium(Na),magnesium(Mg),zinc(Zn),fluorine(F),chlo-rine(Cl),potassium(K)andsilicon(Si)[12].
Thus,whentheforeignmaterialsareimplantedinthehumanbody,theyencounterahostilecorrosiveenvironmentcomprisingofvariousmediasuchasblood,water,Na,Cl,plasma,aminoacids,andmucininsaliva[13].
Inorganicmetaloxidesuchastitaniumoxide(TiO2)anditsalloysarecommonlyusedindentalimplantsduetoitsfavourablebiocompatibilityandmechanicalproperties.
Theabilityoftheoxidelayeroftitanium(Ti)towithstandthecorrosioninsalineandacidicenvironmentmakeitanexcellentimplantmaterialincreasingthechanceofre-osseointegration[14].
However,afterlongterminteractionwithlivingtissue,theTiO2willreleasesmallamountsofcorrosionproductsandleadtodentalimplantcontamina-tion[14].
Corrosionduetobodilyfluidscancausechangesinmaterialstructureandreleaseofunwantedinflamma-toryby-products,andcompromiseimplant'smechanicalstability[15].
Dentalimplantsmayalsobecontaminatedwhentheyaremarketed,i.
e.
priortoanycontaminationfromtheoralcavity.
Therefore,thereisapossibilitythatcontaminationsmayalsodependonothermattersthanbiologicalinsitueffects.
Therefore,sterilepackagedmedicaldevicesmustbeperiodicallyreviewedanddocumentedbythemanu-facturesthattheimplantsarefreeofsurfaceimpurities[16].
Anothercauseofdentalimplantcontaminationisgal-vaniccorrosion.
Thisisanelectrochemicalprocessthatoccurswhenelectronscanflowfreelybetweentwodif-ferentmaterialswithsufficientlydifferentelectricalpoten-tials[17].
Thekeycircumstancesthatcouldinfluencetheini-tialhealingphaseoftheimplantsiteandthesurvivalrateofdentalimplantsarethesurgicalfactors,thetimeofimplantsurgery,siteofimplantplacement,typeofimplantosteotomy,implantdesignandimplantstabil-ity[18].
Thesefactorsheavilyinfluencetheprobabilityofexposuretocontaminants.
Thesecontaminantsmaycausedentalimplantstofailintheirfunctiontorestoremissingteeth.
Also,thereisandalsocauseafinancialburdentothepatientandthehealthcareservicestoinvestindecon-taminationmethods.
Therefore,itisimportanttodiscusstheaetiologyofdentalimplantfailures.
Inthisreview,wediscusstwomajortypesofcontaminants:theinorganicandorganiccontaminantsincludingbacterialcontami-nants.
ThisreviewalsoaimstodiscussthepotentialeffectofthesecontaminantsonTidentalimplants.
2Inorganiccontaminants2.
1Reactiveoxygenandnitrogenspecies(RONS)Reactiveoxygenandnitrogenspecies(RONS)arefreeradi-calsandreactivemoleculesderivedfrommolecularoxy-genandnitrogenspecies,bothasintercellularaswellasintracellularmessengers.
AscanbeseeninTable1,RONScanbefoundinlasers(i.
e.
LLLT-low-levellasertherapy),photosensitizers,bleachingagents,coldplasma,andresincementasaby-productfromdentalapplications[19].
AtlowormoderateconcentrationofRONS,ithasbeneficialeffectswhichresultsintheangiogenesis(formationofnewbloodvessels),proliferationandre-epithelialisationofcellsinthegingivalandothertissuesofthebody,andvascularendothelialgrowthfactor(VEGF)inducedcellmigration[18].
However,atveryhighlevelsofreactiveoxygenspe-cies(ROS),adverseeffectsmayrisecausingperi-implantinflammation,carcinogenesis&mutagenesis,mitochon-drialdysfunctionandcelldeath[19,20].
2.
2Calcium(Ca)AlargeamountoftheCacontaminationwasfoundinthesodiumhydroxide(NaOH)reagent[21].
Kizukietal.
[21]verifiedthattreatmentofTiwithNaOHreagentandheattreatmentsinducedapatiteformationwithbone-bondingabilitywithTimetal.
Unfortunately,withincreasingvolumeofNaOHreagent,theapatiteformationwasdecreasedduetoCacontaminationfoundintheNaOHreagent.
TheCainhibitedapatiteformationontheTimetalinSBF(Syn-thetic/SimulatedBodyFluid)bysuppressingNaionreleasefromthesodiumtitanateintothesurroundingfluid.
EvenaCacontaminationlevelof0.
0005%oftheNaOHrea-gentwassufficienttoinhibittheapatiteformation[21].
ExposureofTitosimulatedphysiologicalsolutions(i.
e.
Ringer'ssolutionandsaline,whichcontainscalciumandphosphateions)leadstoadsorptionofcalciumphosphateSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperTable1ListoforganicandinorganiccontaminantsonTidentalimplantsandtheirpotentialentryandeffectsondentalimplantsNatureofcontaminantsContaminantPotentialentryPotentiallybeneficialeffectPotentiallydangerouseffectReferencesInorganiccontaminantsReactiveoxygenandnitrogenspecies(RONS)Low-levellasertherapy[19]Photosensitizers[19]Bleachingagents[19]Coldplasma[19]Resincement[19]Angiogenesis[19]Proliferationandre-epithelializationofcells[19]VascularEndothelialGrowthFactor(VEGF)inducedcellmigration[19]Peri-implantinflammation[20]Celldeath[19]Carcinogenesis&mutagenesis[19]Mitochondrialdysfunction[19][19,20]CalciumNaOHreagent[20]Physiologicalsolution(Ringer'ssolu-tionandsaline)[15]Improvedbonecontactandresultsingoodosseointegration[22]Inhibitapatiteformation[21][15,21,22]PhosphorusAnodizationinphosphoricacidsolu-tion[11]Calciumphosphatecoating[24]Biologicalresidue(oralcavity)[25]Modulatecytokinesproduction[23]Promotestemcelldifferentiation[24]Increaseosteoblastsproduction[24]Increaseboneformation[24]WhiteresidueobstructingTiimplant[25][2,11,23–25]PhosphorusAnodizationinphosphoricacidsolu-tion[11]Calciumphosphatecoating[24]Biologicalresidue(oralcavity)[25]Modulatecytokinesproduction[23]Promotestemcelldifferentiation[24]Increaseosteoblastsproduction[24]Increaseboneformation[24]WhiteresidueobstructingTiimplant[25][2,11,23–25]ChlorineHClsolution[26]Low-levelFrequencyUltrasoundTreat-ment[27]Saliva[17]CleanTisurface(HCl)[26]Creatinganacidicenvironment[17]Attacktheoxidationlayer[17]Corrodeimplant-abutmentconnec-tion[17][17,26,27]SulphurSandblasting[31]Acidetchingprocess[32]Sulphuricacid[26]Doubleacidetchingtreatment:Pro-duceddualroughnessTi,improvedosteoblastadhesion,proliferationanddifferentiation[32]DisturbthechemicalmodificationofTisurface[26][26,31,32]SodiumSaline[28]Sodiumhypochlorite[26]Sodiumhydroxide[33]Improveosteoconductionandosteoin-tegration[33]Enhanceearlystageofcelladhesion,proliferation,anddifferentiation[34]Causeprecipitationofmanyminerals,higherwearresistanceoftheimplantsurface[28,33–35]AluminiumSand-blasting[37]Acidetching[37]Physiologicalfluids[15]Ti–Alcoating[38]Enhancecorrosionresistant[15]Improvedosteoblastviability[22]Interfereosseointegrationprocess[39][15,22,37–39]SiliconPassivationprocessSisol–gelcoatingTi[43]Fabricationprocess,cleaningandsterilizationprocess[36]Environmentduringhandlingandstor-age(glassvials)[36]Analysispreparation[36]Promoteosteoblastdifferentiation[41,42]StimulatescollagentypeIsynthesis[41,42]Allowedhumancelladherence[41,42]Mineralizationofhumantissue[41,42]Increaseosteoinductiveproperties[43]Preventbacterialinfectionafterimplantation[44]Enhanceinflammatoryresponse[36,40]Alterationoftheoxidelayersurface[36,40]Failureinre-osseointegration[36,40][36,40–44]ReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4NAnotavailableTable1(continued)NatureofcontaminantsContaminantPotentialentryPotentiallybeneficialeffectPotentiallydangerouseffectReferencesZincToothpaste[40]Mouthwash[40]Increasingthecellproliferationinosteoblasts,boneformationandbiomineralization[46]AntibacterialpropertyPro-angiogenic[1]Goodosteoinductivity[1]Allergicreactiontometal[45][1,40,45,46]FluorineToothpaste[14,47]Mouthwash[14,47]Prophylacticgels[14,47]Acid-etchingprocess[47]Preventdentalcariesdevelopment[14,47]Relievedentalsensitivity[14,47]DegradedtheprotectiveoxidelayerofTianditsalloys[14,47]DiscolourationofTiimplants[17][14,17,40,47]HydrogenAcid-etching[13]Biologicalenvironmentoforalcavity[50]DelayedfracturedonTiimplant[50]ImproveOsteoblasts(Si–Hcoating)[51]Keratinocytesadhesionandviability[51]EmbrittlementoftheTisurfacelayer[13][13,50,51]OrganiccontaminantsHydrocarbonAir[53]Water[53]Cleaningfluid[53]NALessenosteoblastattachment[52]ReducedhydrophilicityofTi[52][52,53]CaboxylatesCoatingofTisurface[54]Osteoblastproliferation,differentia-tion,andmatrixmineralization[54]Increasethe(super-)hydrophilicityofTianddecreasedthebondingwiththeoxide,N,andSatomsonprotein[31]Reducedtheattachmentofcells[31][31,54]SaltsoforganicacidsGlycolysisofbacteria[55]NAReducedpH–favourableforaerobicbacteria[55]Corrosion[55]DiscolourationofTiimplants[55][55]Nitrogenfromammoniumresi-duesBacterialplaque[2]Bolus[2]Saliva[2]InhibitgrowthofE.
coliandactasanoxidantforthecombustionreaction[56]WhiteresidueobstructstheTisurface[2][2,56]BacteriaMicrobesinoralcavity[57]Bacterialcontaminationduringsurgery[58]NADamagedtheTiO2layer[57]Microbialcorrosion[14,17]Inflammation[14]Peri-implantitis[17][14,17,57,58]SNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperonthesurfaceoftheoxidelayer,spontaneously[15].
Pos-itivelychargedCaionsattachedtonegativelycharged(PO4)3and(CO3)2actingasnucleationsitesforapatiteandimprovingbonetoimplantcontact,thusresultingingoodosseointegration[22].
2.
3Phosphorus(P)ChemicalcompositionofthesurfaceoftheTidentalimplantsplaysanimportantrolecreatingasurfacewherethebonecellscanattachwellthusallowingosseointegra-tiontooccur.
Astudyhadbeenconductedtoexaminethesurfacephosphoruscontentsofanodizedmedical-gradeTisamples[11].
TheTisampleswereanodisedinphosphoricacidsolutionatdifferentvoltages(10V,20V,30Vor40V)andcreatedTiO2layersonthesurfaces.
Anodisationinphosphoricacidsolutionincreasesthephosphorcontentofthesurfacemaypromoteosseointegrationandleadtosecondarystabilityforthedentalimplants[11].
Furthermore,dentalimplantsurfacestreatedwith37%phosphoricacidmodulatescytokineproductionbybloodmononuclearcells,establishingabalancebetweenpro-teinswithantiandpro-inflammatoryactivity,thuspro-motingthesuccessofdentalimplants[23].
ATisurfacecoatingbasedoncalciumphosphateshowedhighhydro-philicityandhighosseointegration,promotingstemcelldifferentiation,increasingosteoblastproductionandboneformation,thusresultinginincreasingboneformationinashortertime[24].
OnestudycharacterizedthesurfaceofTihealingabut-mentsbeforeandafterclinicalplacementtoinvestigatetheeffectsoftheoralenvironmentondevicesurfaces[25].
TheresearchersfoundathickwhiteresiduecontainingC,N,O,CaandPcompletelyobstructingtheTisurface.
TheysuggestedthatthepresenceofPcontaminantcamefrombiologicalresidueoftheoralcavity.
2.
4Chlorine(Cl)Hydrochloricacid(HCl)wasusedtocleantheTisurface.
However,aminimalamountofClwasdetectedontheimplantsurfaces.
Fortunately,smallamountofCldidnotweakentheTisurfacesastheClformedTi-Clcomplexandsolubleinwater[26].
Anotherpotentialcontamina-tionbyClwasfromsonicatedsolutionoflow-frequencyultrasound(usedtotreatchronicallyinfectedwounds).
ThesonicationsolutionfromtheultrasoundtreatmentwasabletoaltertheTisurfacechemistry,depositingClaswellasCa,aluminium(Al),Si,NaandKontheimplantsurface[27].
SalivacontainsK,Na,N,chloride,bio-actonateproductsandproteins.
However,duringcrevicecorrosion,thecon-centrationofchlorideionsincreasesandreducesthepHvalueofsalivacreatinganacidicenvironment.
Thechlorideionsattacktheoxidationlayerofdentalimplantsleadingtoacorrodedimplant-abutmentconnection[17].
Hence,sterilesalinecanbeusedtoreducetheminimaltracesofchlorideonimplantsurface[28].
However,ClcanbecompletelyremovedfromtheTiimplantsurfaceseitherbyrinsingorultra-sonication,bothinultra-purewater[29].
2.
5Sulphur(S)Sulphur(S)compoundsaswellasNa,K,Ca,PO4,CO2andmucincanbefoundinthemouth[30].
Tracesofsulphatesalongwithfluorides,magnesiumoxides,silicates,andcal-ciumoxidesarefoundasaresultofthesandblastingandetchingprocessoftheimplantsurfaces[31].
Hydrochloricacid(HCl)andsulphuricacids(H2SO4)arefrequentlyusedtopre-treatedTisurfaces.
SfromtheresidualS2O82orSO42wasdetectedfromthesamplestreatedwitheitherSodiumpersulfate(Na2S2O8)orH2SO4.
However,theTi-acidcomplexes(titaniumsulfate)waslessdissolvedinwater,thusnotsuitablefordecontaminationofTisurfacesasitcandisturbthechemicalmodificationofTisurface[26].
Gineretal.
demonstratedthatadoubleacidetch-ingtreatmentusinghydrofluoricacidfollowedbysulfuricacidproducedadualroughnessTisurfacewhichimprovedosteoblastadhesion,proliferationanddifferentiationthusenhancingosseointegration.
ScanbecompletelyremovedfromtheTisamplesbythenon-thermalplasmatreatmentbutnotbyUVtreatment[32].
2.
6Sodium(Na)TracesofNahavealsobeenreportedonimplantsurfaceswhichhavebeentreatedwithsodium-containingsolu-tionssuchassalineandsodiumhypochlorite,withsodiumhypochloritecausingatenfoldhigheramountoftraceNathansaline[28].
NaOHhasbeenusedinalkalinetreat-menttocreateasodiumtitanatelayerbyincorporatingNaionsontotheTisurface.
Thenanoporoushydroxyapatite/sodiumtitanatebilayerhasbeenreportedtoimprovein-vivoosteoconductionandosteointegration[33].
Moreo-ver,thetreatmentofhydrophilicityofTidiscsusingNaOHtendtoenhancetheearlystagesofcelladhesion,prolif-eration,anddifferentiation[34].
Inonestudy,SBFsolutionhasbeenusedduringacoatingprocedureforTiimplants,causingprecipitationofmanyminerals(e.
g.
Na,Ca,Mg,P)presentedinthesolution,whichleadstoahigherwearresistanceoftheimplantsurface[35].
AstudydonebyShiblietal.
revealedtracesofNacontaminantalongwithcarbon,O,N,Ca,Al,andOontheTisurfaceofthefailedimplants.
TheinfluenceofthecontaminantsblockthesitesfortheoxygencathodicreactionthuspreventingforeignionssuchasironorchromiumtocatalysetheoxygenReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4reaction.
Hence,causinganincreaseinthedissolutionrateofTiimplantsandpreventingre-osseointegration[36].
2.
7Aluminium(Al)SurfaceanalysisofTiimplantsusingX-rayPhotoelectronSpectroscopy(XPS)measurementsrevealedthepresenceofAlandfluoridewhichweredepositedduringthesand-blastingandacidetchingprocess[37].
TheoxidizedstateofAl,(alumina)isconsideredtobestableinphysiologi-calfluidswithveryminortissuereaction.
Therefore,ithasbeenusedasacoatingmaterialtoenhancethecorrosionresistancecharacteristicsofdentalimplants[15].
Inaddi-tion,favourablecellreactionswereobservedforaroughTisurfaceenrichedwithAl,CaandPions,whenincorpo-ratedintotheTisurfaceappearstoimproveviabilityofosteoblasts[22].
SomeTidentalimplantsmaycontainsurfacecontami-nantsthatmaycauseaproblemduringtheosseointegra-tionprocess.
AstudydonebySemezetal.
[38]showedthattheamountofAlinadentalimplantcalledMYIM-PLANT(NobelBiocare,India)was12-foldhigherthanthatfoundinTialloystypicallyusedfordentalimplants(between0andabout0.
06)[38].
Furthermore,anotherstudysuggestedthatahighconcentrationofresidualaluminiumoxide(AlO2)mayinterferenegativelywiththeosseointegrationprocess[39].
2.
8Silicon(Si)SiwasdetectedonthefailedimplantsalongwithP,Ca,Na,S,Cl,Znandcopper(Cu)ontheTisurface.
Ithasbeensuggestedthatthesurfacecontaminantsmayenhancetheinflammatoryresponse,alteringthehealingprocesswhichleadstoalterationoftheoxidelayersurfaceandfailureinreosseointegration.
ThepresenceofSiispossi-blyduetothepassivationprocesswheretheSiwasusedasacoatingorintreatingTisurfaces[36,40].
Otherthanthepassivationprocess,Simaycomefromiondissolutionfromtheglassstoragevialsorprobably(lesslikely)fromrubbergloves.
Itmayalsooriginatefromthefabricationprocess,cleaningandsterilizationprocess,thehandlingenvironmentandstorage(glassvials)andanalysisprepa-rationprocedures[36].
Nevertheless,Siplaysanessentialelementinbonemetabolismincludingpromotingosteoblastdifferen-tiation,stimulationofcollagentypeIsynthesis,allowinghumancelladherenceandmineralizationofhumantis-sue[41,42].
Assuch,SihasbeenusedasacoatingonTidentalimplantsformingaSisol–gelcoatingTi.
AstudydonebyMartnez-Ibanezetal.
[43]showedthattheincor-porationoftetraethylorthosilicate(TEOS)tothesol–gelSicausedhydrolyticdegradationthatleadstoreleasingofSicompoundtothemedia.
ThisresultedinanincreaseintheeffectofosteoinductivepropertiesallowingfordirectcontactbetweennewboneandtheTiimplant[43].
Silicon-basedcoatingshavepropertiesinpreventingbac-terialinfectionpost-implantationandthereforeimprovedpatientoutcomes[44].
2.
9Zinc(Zn)DentalimplantsmadeofZnwerereportedtocauseden-talmetalallergyinJapan[45].
SomeofthetracesofZnioncanbefoundasthismetalisaddedtotoothpasteandmouthwashsolutionsasanti-plaqueagents.
Thisactiv-ityisbelievedtobeduetoretentionin'oralmicroreser-voirs'suchassoftoraltissues,toothsurfacesandbacterialplaque[40].
Nevertheless,Znhasbeenrecognizedasanimportanttraceelementinincreasingthecellproliferationinosteoblasts,boneformationandbiomineralization.
Inaddition,Znhasantibacterialpropertiestherefore,attract-ingresearcherstoincorporatetheZnintoTisurfacesindentalimplantstoenhancebioactivity.
Co-implantedZnandMgionsintoTiimplantsshowedgoodosteoin-ductivity,pro-angiogenicandbacterialeffectswhichcanenhancerapidosseointegration[1,46].
2.
10Fluorine(F)TracesofFandScanbefoundduringtheacid-etchingpro-cess[40].
Fluorideions(upto0.
1wt%)canalsobefoundincommercialtoothpaste,mouthwashsolutionsandpro-phylacticgels.
Itsfunctionsaretopreventdevelopmentofdentalcariesandtoalleviatedentalsensitivity.
How-ever,highconcentrationsoffluorideionsexhibitnegativeeffectsontheprotectiveoxidelayerofTianditsalloys,triggeringlocalizedcorrosivedegradation.
ThedegreeofcorrosionofTianditsalloysaredependsontheconcentra-tionoffluorideionsandthepHofthefluoride-containingenvironments[14,17,47].
Besides,ataconcentrationsof3ppmoffluorideions,Tialloybecomesdiscolouredandataconcentrationabove20ppm,theprotectiveoxidelayerbecomesdegraded[47].
DiscolorationofTiimplantscanbeobservedafterundergoingautoclavingduetoFcon-tamination[48].
2.
11Hydrogen(H)Anacidetchingtechniqueispopularlyusedbymanufac-turerstotexturethesurfaceofdentalimplants.
Combi-nationofacidssuchashydrofluoricacid-nitricacidareoftenusedtoremovetheoxidelayerofTisurfaces.
InthehydrofluoricacidpretreatmentofTisurfaces,theformerattackstheoxidelayerandreactswithTitoformsolubleTifluoridesandH.
WhenthefreeHissaturated,titaniumSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperhydrideisformed.
ThetitaniumhydridecandramaticallyaffectthemechanicalpropertiesofTiwhichcauseembrit-tlementofthesurfacelayer.
However,byaddingnitricacid,itcanreducefreeHformation[13,49].
AstudyonthefracturesurfaceofretrievedTiscrewthreadsrevealedahighamountofHabsorptionfrombiologicalenvironmentoforalcavitytocausedelayedfractureofaTiimplant[50].
AsynergisticroleofSiandHcoatingimprovestheirinteractionwithosteoblasts.
AstudydonebyMussanoetal.
[51]revealedthathydrogen-richfilmsincreasedkeratinocytesadhesionandviabilitythusenhancingosseointegration.
3Organiccontaminants3.
1HydrocarbonsThecontaminationofTiimplantsurfacestakesonly4weeksforthefreshlycutorpreviouslyphoto-function-alizedimplantstobecoveredwithhydrocarbonsnomat-terthetypeofsurfacetreatmenttheyhaveundergone[37].
ThepresenceofhydrocarbonontheTisurfacemaylessenosteoblastattachmentasthecelladhesionproteincannotattachtosuchsites[52].
Moreover,hydrocarbonfoundintheair,water,orcleaningfluidcanbecontinu-ouslyadsorbedontotheTisurfaceandsignificantlyreducethehydrophilicityofTiduringstorage[53].
Photo-func-tionalizationhasproventobeavalidmethodtoreducetheamountofhydrocarboncontaminationonTidentalimplantsandimproveosseointegration[37].
3.
2CarboxylatesCarboxylatescanbefoundfromthecoatingofTisurfaces.
Carboxylatedmulti-walledcarbonnanotubecoatedTihasbeenshowntohaveincreasedosteoblastproliferation,differentiation,andmatrixmineralization[54].
However,carboxylatescontaminantscancauseadverseeffectsonTisurface.
Highamountsofcarboxylgroupsfromcarbox-ylatesandhydrocarboncanincreasethe(super)hydro-philicityofTi.
Thissubsequentlydecreasethebondingwiththeoxide,N,andSatomsonproteinandreducetheattachmentofcells.
Inordertoremovethecarboxylatecontaminant,high-energyphotonssuchasnon-thermalplasmaandUVlightarerequiredtobreaktheweakbondsbetweencarboxylgroupsandTi[31].
3.
3SaltsoforganicacidsTheproductionoforganicacidscomefromthepro-cessofglycolysisbybacteriaandmayreducepHtocreateafavourableenvironmentforaerobicbacteria.
Accumulationoforganicacidsleadstoanacidicenvi-ronmentandinducescorrosionanddiscolourationofTiimplants[55].
3.
4NitrogenfromammoniumresiduesPresenceofsubstances,likeN,C,O,Ca,andP,foundonthesurfaceoftheTihealingabutmentsformawhiteresidue.
ThesewhiteresiduescauseobstructionontheTisurface.
TheexistenceofNandotherelementsresiduemaycomefrombacterialplaque,bolus,soft-tissueorproteincom-poundsinsalivathathaveadheredtotheTisurface[2].
Inaddition,bacterialbiofilmincreasedthepercentageofbothcarbonandnitrogenontheTisurface.
ByusingH2O2photolysis,thedegradedbiocompatibilityofbiofilm-con-taminatedTisurfacescanberecoveredandmayhavethepotentialforimprovingperi-implantitis[52].
Astudyreportedthatthemicrowave-assisteddryingofHA(hydroxyapatite)sampleswerefoundtobeeffectiveininhibitingthegrowthofEscherichiacoli.
Theformationofammoniumnitrateduringthedryingprocesswhencal-ciumnitrateandammoniawereaddedintothesolutionforTiO2synthesis.
Theresultant,ammoniumnitrate,actsasanoxidantforthecombustionreaction[56].
3.
5BacteriaBacterialcolonizationcandamagethesurfaceTiO2layer.
Astudyreportedthatthecolonizationofbacteriademon-stratesmoreprominentdamageonthesurfacemorphol-ogyandchemistryofimplantsurfaces[57].
Bacteriacancausemicrobialcorrosionwheretheacidicwasteproductscreatedbymicrobesgenerateanacidicenvironment.
Thecorrosionmayleadtoinflammationandoccurrenceofperi-implantitis.
Theseverityofmicrobialcorrosioncanbereducedbyusingantibioticspraysanddipstominimizemicrobepopulations[14,17].
Bacterialcontaminationcanoccurondentalimplantsduringsurgeryandaffecttheosseointegrationandtheprognosisinaclinicallysig-nificantway;howeverscientificevidenceinasystematicreviewconcerningthisisinsufficient[58].
Combinedusageofantisepticssuchaschlorhexidinedigluconate(CHX)orhydrogenperoxideH2O2andpho-todynamictherapy(PDT)wasmoreeffectiveineliminat-ingbacteriabiofilm.
ThiswassupportedbyastudywherethecombinationofantisepticsandPDTshowedeffectivedecontaminationabilityineradicatingStaphylococcusaureusbiofilmfromTisurfaces[59].
Despiteawiderangeoforganicandinorganicimpu-ritiesthatmaycontaminatedentalimplantsurfaces,the10yearclinicalsurvivalrateofthemostcommonlyusedoralimplantsisintherangeof90–95%andtheresultsofReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4"modern,moderatelyroughoralimplantsarebetween95and99%at10years.
[60].
4ConclusionThisreviewistargetedatbothmanufacturersandclini-cians.
Contaminationsofdentalimplantsareintimatelyassociatedwithimplantfailures.
Fromthesummariza-tionofthereview(seeTable1),thecontaminantsmaybecomebeneficialand/orproducedisastrouseffectsondentalimplants.
Thesemayalterthesurfaceenergy,chemicalpurity,thicknessandcompositionoftheoxidelayer.
ItisalsoknownthatthemostcommonelementalcontaminationofTisurfaces,potentiallylinkedtoimplantfailuresaretraceelementssuchasN,Ca,P,Cl,S,Na,SiandF,someorganiccarbonsandbacterialcells/by-products.
However,someofthecontaminantssuchasSiandParebeneficialtothedentalimplantsthatpromoteosseointe-gration.
Thetracesoforganicandinorganiccontaminantscanbefoundfromtheimplantcleaningprocess,Tisurfacetreatmentsuchasacid-etchingandsand-blasting,biologi-calenvironmentandalsothesurroundingenvironment.
Variousmethodsofremovingcontaminantsarealsointro-ducedwiththehopeofpromotingosseointegration.
AcknowledgementsThisstudyissupportedbytheUniversityResearchCouncilunderUniversitiBruneiDarussalamwiththeGrantNumberUBD/RSCH/URC/RG(b)/2018/004,ledbyDrJagjitSinghDhaliwal(PrincipalInvestigator).
CompliancewithethicalstandardsConflictofinterestTheauthorsdeclarethattheyhavenoconflictofinterest.
OpenAccessThisarticleislicensedunderaCreativeCommonsAttri-bution4.
0InternationalLicense,whichpermitsuse,sharing,adap-tation,distributionandreproductioninanymediumorformat,aslongasyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinktotheCreativeCommonslicence,andindicateifchangesweremade.
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Ifmaterialisnotincludedinthearticle'sCreativeCommonslicenceandyourintendeduseisnotpermittedbystatutoryregulationorexceedsthepermitteduse,youwillneedtoobtainpermissiondirectlyfromthecopyrightholder.
Toviewacopyofthislicence,visithttp://creativecommons.
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EurJOralImplant11:123–136Publisher'sNoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.
org/10.
1007/s42452-020-2810-4ReviewPaperContaminationoftitaniumdentalimplants:anarrativereviewJagjitSinghDhaliwal1·ShebaRaniNakkaDavid1·NurulRamizahZulhilmi1·SachinjeetKaurSodhiDhaliwal1·JoeKnights1·RubensFerreiradeAlbuquerqueJunior2Received:13November2019/Accepted:22April2020TheAuthor(s)2020OPENAbstractContaminationoftitaniumdentalimplantsmayleadtoimplantfailure.
Therearetwomajortypesofcontaminants:theinorganicandorganiccontaminants.
Theinorganiccontaminantsmostlyconsistofelementssuchascalcium,phos-phorus,chlorine,sulphur,sodium,silicon,fluorineandsomeorganiccarbons.
Whereasorganiccontaminantsconsistofhydrocarbon,carboxylates,saltsoforganicacids,nitrogenfromammoniumandbacterialcells/byproducts.
Contami-nantscanalterthesurfaceenergy,chemicalpurity,thicknessandcompositionoftheoxidelayer,however,welackclini-calevidencethatcontaminationshaveanyeffectatall.
However,surfacecleanlinessseemstobeessentialforimplantosseointegration.
Thesecontaminantsmaycausedentalimplantstofailinitsfunctiontorestoremissingteethandalsocauseafinancialburdentothepatientandthehealthcareservicestoinvestindecontaminationmethods.
Therefore,itisimportanttodiscusstheaetiologyofdentalimplantfailures.
Inthisnarrativereview,wediscusstwomajortypesofcontaminants:theinorganicandorganiccontaminantsincludingbacterialcontaminants.
ThisreviewalsoaimstodiscussthepotentialeffectofcontaminationonTidentalimplants.
KeywordsDentalimplant·Contamination·Prognosis·Titanium1IntroductionDentalimplantscangetcontaminatedduetotheecologi-calsystemintheoralcavitywithabundantmicroorgan-isms[1].
Commonelementalcontaminationfromorganiccarbonandtracesofelementsincludingoxygen(O),nitrogen(N),calcium(Ca)andphosphorus(P)foundondentalimplantsurfacesarepotentiallylinkedtofailureinre-osseointegrationwhenpartsofanimplanthadlostitsosseointegration[2].
Ithasbeenshownre-osseointegra-tionoccurswhenthereisaformationofadirectstructuralandfunctionalunionbetweenanimplantandbone,ithasbeenshownthatproperlycleanedimplantsindeedmayre-osseointegrate[3].
Henceseveralfactorssuchassurfacetopography,chemicalpurity,thicknessandcompositionoftheoxidelayer,surfacecleanliness,andtheexistenceofmetallicandnon-metalliccompoundsonthesurfaceseemstoinfluencethesuccessofimplantosseointegra-tion[4].
Currently,agrowingamountofevidence[5,6]sug-geststhattheimplantsurfacetopographyandchemistryhasgreatinfluenceontheosseointegrationprocessbyaffectingproteinsignallingandcellmigrationordiffer-entiation.
Bone-implantcontactarea,mechanicalinter-lockingandstressdistributionarerecognisablybetterinsurfaceswithacertaindegreeofroughnessincomparisontosmoothones,favouringosteoblast-likecellcolonisa-tion[7].
However,ithasalsobeenshownthatroughenedsurfacesenhancetheaccumulationofcontaminants[8].
Nevertheless,themechanismsbywhichinorganicandorganiccontaminantsinteractwiththeimplantsurfacesremainundefined.
Althoughmanymethodsofimplant*JagjitSinghDhaliwal,jagjit.
dhaliwal@ubd.
edu.
bn|1PengiranAnakPuteriRashidahSa'adatulBolkiahInstituteofHealthSciences,UniversitiBruneiDarussalam,JalanTungkuLink,Gadong,BruneiDarussalam.
2DepartamentodeMateriaisDentáriosEPrótese,FaculdadedeOdontologiadeRibeiroPreto,UniversidadedeSoPaulo,SoPaulo,Brazil.
ReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4decontaminationhavebeenattempted,noneofthemhavesucceededinproducingpredictableresults.
Implantsurfacedecontaminationremainschallengingandthusthedevelopmentofnew,effectivemethodsisnecessary[9,10].
Topographicalmodificationisfrequentlyadoptedintitanium-basedimplantstoproducethedesiredsurfacepropertiesbyusingdifferentsurfacetreatmentssur-facetreatmentssuchassandblasting,chemicaletching,anodization,lasertreatment,andsurfacecoatings[11].
Althoughthesesurfacetreatmentscanchangetheprop-ertiesoftheimplantsurfacesandonrareoccasions,mayalsoleadtoundesiredpropertiesandhence,contamina-tionoftheimplantsurfaces.
Humanbodyfluidscontaintraceelementssuchaschlorineandfluorideionswhereasourbonecompriseofcollagen,hydroxyapatite(Ca10(PO4)6(OH)2),andsomeani-onicandcationicsubstituentssuchascarbonates(H2CO3),sodium(Na),magnesium(Mg),zinc(Zn),fluorine(F),chlo-rine(Cl),potassium(K)andsilicon(Si)[12].
Thus,whentheforeignmaterialsareimplantedinthehumanbody,theyencounterahostilecorrosiveenvironmentcomprisingofvariousmediasuchasblood,water,Na,Cl,plasma,aminoacids,andmucininsaliva[13].
Inorganicmetaloxidesuchastitaniumoxide(TiO2)anditsalloysarecommonlyusedindentalimplantsduetoitsfavourablebiocompatibilityandmechanicalproperties.
Theabilityoftheoxidelayeroftitanium(Ti)towithstandthecorrosioninsalineandacidicenvironmentmakeitanexcellentimplantmaterialincreasingthechanceofre-osseointegration[14].
However,afterlongterminteractionwithlivingtissue,theTiO2willreleasesmallamountsofcorrosionproductsandleadtodentalimplantcontamina-tion[14].
Corrosionduetobodilyfluidscancausechangesinmaterialstructureandreleaseofunwantedinflamma-toryby-products,andcompromiseimplant'smechanicalstability[15].
Dentalimplantsmayalsobecontaminatedwhentheyaremarketed,i.
e.
priortoanycontaminationfromtheoralcavity.
Therefore,thereisapossibilitythatcontaminationsmayalsodependonothermattersthanbiologicalinsitueffects.
Therefore,sterilepackagedmedicaldevicesmustbeperiodicallyreviewedanddocumentedbythemanu-facturesthattheimplantsarefreeofsurfaceimpurities[16].
Anothercauseofdentalimplantcontaminationisgal-vaniccorrosion.
Thisisanelectrochemicalprocessthatoccurswhenelectronscanflowfreelybetweentwodif-ferentmaterialswithsufficientlydifferentelectricalpoten-tials[17].
Thekeycircumstancesthatcouldinfluencetheini-tialhealingphaseoftheimplantsiteandthesurvivalrateofdentalimplantsarethesurgicalfactors,thetimeofimplantsurgery,siteofimplantplacement,typeofimplantosteotomy,implantdesignandimplantstabil-ity[18].
Thesefactorsheavilyinfluencetheprobabilityofexposuretocontaminants.
Thesecontaminantsmaycausedentalimplantstofailintheirfunctiontorestoremissingteeth.
Also,thereisandalsocauseafinancialburdentothepatientandthehealthcareservicestoinvestindecon-taminationmethods.
Therefore,itisimportanttodiscusstheaetiologyofdentalimplantfailures.
Inthisreview,wediscusstwomajortypesofcontaminants:theinorganicandorganiccontaminantsincludingbacterialcontami-nants.
ThisreviewalsoaimstodiscussthepotentialeffectofthesecontaminantsonTidentalimplants.
2Inorganiccontaminants2.
1Reactiveoxygenandnitrogenspecies(RONS)Reactiveoxygenandnitrogenspecies(RONS)arefreeradi-calsandreactivemoleculesderivedfrommolecularoxy-genandnitrogenspecies,bothasintercellularaswellasintracellularmessengers.
AscanbeseeninTable1,RONScanbefoundinlasers(i.
e.
LLLT-low-levellasertherapy),photosensitizers,bleachingagents,coldplasma,andresincementasaby-productfromdentalapplications[19].
AtlowormoderateconcentrationofRONS,ithasbeneficialeffectswhichresultsintheangiogenesis(formationofnewbloodvessels),proliferationandre-epithelialisationofcellsinthegingivalandothertissuesofthebody,andvascularendothelialgrowthfactor(VEGF)inducedcellmigration[18].
However,atveryhighlevelsofreactiveoxygenspe-cies(ROS),adverseeffectsmayrisecausingperi-implantinflammation,carcinogenesis&mutagenesis,mitochon-drialdysfunctionandcelldeath[19,20].
2.
2Calcium(Ca)AlargeamountoftheCacontaminationwasfoundinthesodiumhydroxide(NaOH)reagent[21].
Kizukietal.
[21]verifiedthattreatmentofTiwithNaOHreagentandheattreatmentsinducedapatiteformationwithbone-bondingabilitywithTimetal.
Unfortunately,withincreasingvolumeofNaOHreagent,theapatiteformationwasdecreasedduetoCacontaminationfoundintheNaOHreagent.
TheCainhibitedapatiteformationontheTimetalinSBF(Syn-thetic/SimulatedBodyFluid)bysuppressingNaionreleasefromthesodiumtitanateintothesurroundingfluid.
EvenaCacontaminationlevelof0.
0005%oftheNaOHrea-gentwassufficienttoinhibittheapatiteformation[21].
ExposureofTitosimulatedphysiologicalsolutions(i.
e.
Ringer'ssolutionandsaline,whichcontainscalciumandphosphateions)leadstoadsorptionofcalciumphosphateSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperTable1ListoforganicandinorganiccontaminantsonTidentalimplantsandtheirpotentialentryandeffectsondentalimplantsNatureofcontaminantsContaminantPotentialentryPotentiallybeneficialeffectPotentiallydangerouseffectReferencesInorganiccontaminantsReactiveoxygenandnitrogenspecies(RONS)Low-levellasertherapy[19]Photosensitizers[19]Bleachingagents[19]Coldplasma[19]Resincement[19]Angiogenesis[19]Proliferationandre-epithelializationofcells[19]VascularEndothelialGrowthFactor(VEGF)inducedcellmigration[19]Peri-implantinflammation[20]Celldeath[19]Carcinogenesis&mutagenesis[19]Mitochondrialdysfunction[19][19,20]CalciumNaOHreagent[20]Physiologicalsolution(Ringer'ssolu-tionandsaline)[15]Improvedbonecontactandresultsingoodosseointegration[22]Inhibitapatiteformation[21][15,21,22]PhosphorusAnodizationinphosphoricacidsolu-tion[11]Calciumphosphatecoating[24]Biologicalresidue(oralcavity)[25]Modulatecytokinesproduction[23]Promotestemcelldifferentiation[24]Increaseosteoblastsproduction[24]Increaseboneformation[24]WhiteresidueobstructingTiimplant[25][2,11,23–25]PhosphorusAnodizationinphosphoricacidsolu-tion[11]Calciumphosphatecoating[24]Biologicalresidue(oralcavity)[25]Modulatecytokinesproduction[23]Promotestemcelldifferentiation[24]Increaseosteoblastsproduction[24]Increaseboneformation[24]WhiteresidueobstructingTiimplant[25][2,11,23–25]ChlorineHClsolution[26]Low-levelFrequencyUltrasoundTreat-ment[27]Saliva[17]CleanTisurface(HCl)[26]Creatinganacidicenvironment[17]Attacktheoxidationlayer[17]Corrodeimplant-abutmentconnec-tion[17][17,26,27]SulphurSandblasting[31]Acidetchingprocess[32]Sulphuricacid[26]Doubleacidetchingtreatment:Pro-duceddualroughnessTi,improvedosteoblastadhesion,proliferationanddifferentiation[32]DisturbthechemicalmodificationofTisurface[26][26,31,32]SodiumSaline[28]Sodiumhypochlorite[26]Sodiumhydroxide[33]Improveosteoconductionandosteoin-tegration[33]Enhanceearlystageofcelladhesion,proliferation,anddifferentiation[34]Causeprecipitationofmanyminerals,higherwearresistanceoftheimplantsurface[28,33–35]AluminiumSand-blasting[37]Acidetching[37]Physiologicalfluids[15]Ti–Alcoating[38]Enhancecorrosionresistant[15]Improvedosteoblastviability[22]Interfereosseointegrationprocess[39][15,22,37–39]SiliconPassivationprocessSisol–gelcoatingTi[43]Fabricationprocess,cleaningandsterilizationprocess[36]Environmentduringhandlingandstor-age(glassvials)[36]Analysispreparation[36]Promoteosteoblastdifferentiation[41,42]StimulatescollagentypeIsynthesis[41,42]Allowedhumancelladherence[41,42]Mineralizationofhumantissue[41,42]Increaseosteoinductiveproperties[43]Preventbacterialinfectionafterimplantation[44]Enhanceinflammatoryresponse[36,40]Alterationoftheoxidelayersurface[36,40]Failureinre-osseointegration[36,40][36,40–44]ReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4NAnotavailableTable1(continued)NatureofcontaminantsContaminantPotentialentryPotentiallybeneficialeffectPotentiallydangerouseffectReferencesZincToothpaste[40]Mouthwash[40]Increasingthecellproliferationinosteoblasts,boneformationandbiomineralization[46]AntibacterialpropertyPro-angiogenic[1]Goodosteoinductivity[1]Allergicreactiontometal[45][1,40,45,46]FluorineToothpaste[14,47]Mouthwash[14,47]Prophylacticgels[14,47]Acid-etchingprocess[47]Preventdentalcariesdevelopment[14,47]Relievedentalsensitivity[14,47]DegradedtheprotectiveoxidelayerofTianditsalloys[14,47]DiscolourationofTiimplants[17][14,17,40,47]HydrogenAcid-etching[13]Biologicalenvironmentoforalcavity[50]DelayedfracturedonTiimplant[50]ImproveOsteoblasts(Si–Hcoating)[51]Keratinocytesadhesionandviability[51]EmbrittlementoftheTisurfacelayer[13][13,50,51]OrganiccontaminantsHydrocarbonAir[53]Water[53]Cleaningfluid[53]NALessenosteoblastattachment[52]ReducedhydrophilicityofTi[52][52,53]CaboxylatesCoatingofTisurface[54]Osteoblastproliferation,differentia-tion,andmatrixmineralization[54]Increasethe(super-)hydrophilicityofTianddecreasedthebondingwiththeoxide,N,andSatomsonprotein[31]Reducedtheattachmentofcells[31][31,54]SaltsoforganicacidsGlycolysisofbacteria[55]NAReducedpH–favourableforaerobicbacteria[55]Corrosion[55]DiscolourationofTiimplants[55][55]Nitrogenfromammoniumresi-duesBacterialplaque[2]Bolus[2]Saliva[2]InhibitgrowthofE.
coliandactasanoxidantforthecombustionreaction[56]WhiteresidueobstructstheTisurface[2][2,56]BacteriaMicrobesinoralcavity[57]Bacterialcontaminationduringsurgery[58]NADamagedtheTiO2layer[57]Microbialcorrosion[14,17]Inflammation[14]Peri-implantitis[17][14,17,57,58]SNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperonthesurfaceoftheoxidelayer,spontaneously[15].
Pos-itivelychargedCaionsattachedtonegativelycharged(PO4)3and(CO3)2actingasnucleationsitesforapatiteandimprovingbonetoimplantcontact,thusresultingingoodosseointegration[22].
2.
3Phosphorus(P)ChemicalcompositionofthesurfaceoftheTidentalimplantsplaysanimportantrolecreatingasurfacewherethebonecellscanattachwellthusallowingosseointegra-tiontooccur.
Astudyhadbeenconductedtoexaminethesurfacephosphoruscontentsofanodizedmedical-gradeTisamples[11].
TheTisampleswereanodisedinphosphoricacidsolutionatdifferentvoltages(10V,20V,30Vor40V)andcreatedTiO2layersonthesurfaces.
Anodisationinphosphoricacidsolutionincreasesthephosphorcontentofthesurfacemaypromoteosseointegrationandleadtosecondarystabilityforthedentalimplants[11].
Furthermore,dentalimplantsurfacestreatedwith37%phosphoricacidmodulatescytokineproductionbybloodmononuclearcells,establishingabalancebetweenpro-teinswithantiandpro-inflammatoryactivity,thuspro-motingthesuccessofdentalimplants[23].
ATisurfacecoatingbasedoncalciumphosphateshowedhighhydro-philicityandhighosseointegration,promotingstemcelldifferentiation,increasingosteoblastproductionandboneformation,thusresultinginincreasingboneformationinashortertime[24].
OnestudycharacterizedthesurfaceofTihealingabut-mentsbeforeandafterclinicalplacementtoinvestigatetheeffectsoftheoralenvironmentondevicesurfaces[25].
TheresearchersfoundathickwhiteresiduecontainingC,N,O,CaandPcompletelyobstructingtheTisurface.
TheysuggestedthatthepresenceofPcontaminantcamefrombiologicalresidueoftheoralcavity.
2.
4Chlorine(Cl)Hydrochloricacid(HCl)wasusedtocleantheTisurface.
However,aminimalamountofClwasdetectedontheimplantsurfaces.
Fortunately,smallamountofCldidnotweakentheTisurfacesastheClformedTi-Clcomplexandsolubleinwater[26].
Anotherpotentialcontamina-tionbyClwasfromsonicatedsolutionoflow-frequencyultrasound(usedtotreatchronicallyinfectedwounds).
ThesonicationsolutionfromtheultrasoundtreatmentwasabletoaltertheTisurfacechemistry,depositingClaswellasCa,aluminium(Al),Si,NaandKontheimplantsurface[27].
SalivacontainsK,Na,N,chloride,bio-actonateproductsandproteins.
However,duringcrevicecorrosion,thecon-centrationofchlorideionsincreasesandreducesthepHvalueofsalivacreatinganacidicenvironment.
Thechlorideionsattacktheoxidationlayerofdentalimplantsleadingtoacorrodedimplant-abutmentconnection[17].
Hence,sterilesalinecanbeusedtoreducetheminimaltracesofchlorideonimplantsurface[28].
However,ClcanbecompletelyremovedfromtheTiimplantsurfaceseitherbyrinsingorultra-sonication,bothinultra-purewater[29].
2.
5Sulphur(S)Sulphur(S)compoundsaswellasNa,K,Ca,PO4,CO2andmucincanbefoundinthemouth[30].
Tracesofsulphatesalongwithfluorides,magnesiumoxides,silicates,andcal-ciumoxidesarefoundasaresultofthesandblastingandetchingprocessoftheimplantsurfaces[31].
Hydrochloricacid(HCl)andsulphuricacids(H2SO4)arefrequentlyusedtopre-treatedTisurfaces.
SfromtheresidualS2O82orSO42wasdetectedfromthesamplestreatedwitheitherSodiumpersulfate(Na2S2O8)orH2SO4.
However,theTi-acidcomplexes(titaniumsulfate)waslessdissolvedinwater,thusnotsuitablefordecontaminationofTisurfacesasitcandisturbthechemicalmodificationofTisurface[26].
Gineretal.
demonstratedthatadoubleacidetch-ingtreatmentusinghydrofluoricacidfollowedbysulfuricacidproducedadualroughnessTisurfacewhichimprovedosteoblastadhesion,proliferationanddifferentiationthusenhancingosseointegration.
ScanbecompletelyremovedfromtheTisamplesbythenon-thermalplasmatreatmentbutnotbyUVtreatment[32].
2.
6Sodium(Na)TracesofNahavealsobeenreportedonimplantsurfaceswhichhavebeentreatedwithsodium-containingsolu-tionssuchassalineandsodiumhypochlorite,withsodiumhypochloritecausingatenfoldhigheramountoftraceNathansaline[28].
NaOHhasbeenusedinalkalinetreat-menttocreateasodiumtitanatelayerbyincorporatingNaionsontotheTisurface.
Thenanoporoushydroxyapatite/sodiumtitanatebilayerhasbeenreportedtoimprovein-vivoosteoconductionandosteointegration[33].
Moreo-ver,thetreatmentofhydrophilicityofTidiscsusingNaOHtendtoenhancetheearlystagesofcelladhesion,prolif-eration,anddifferentiation[34].
Inonestudy,SBFsolutionhasbeenusedduringacoatingprocedureforTiimplants,causingprecipitationofmanyminerals(e.
g.
Na,Ca,Mg,P)presentedinthesolution,whichleadstoahigherwearresistanceoftheimplantsurface[35].
AstudydonebyShiblietal.
revealedtracesofNacontaminantalongwithcarbon,O,N,Ca,Al,andOontheTisurfaceofthefailedimplants.
TheinfluenceofthecontaminantsblockthesitesfortheoxygencathodicreactionthuspreventingforeignionssuchasironorchromiumtocatalysetheoxygenReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4reaction.
Hence,causinganincreaseinthedissolutionrateofTiimplantsandpreventingre-osseointegration[36].
2.
7Aluminium(Al)SurfaceanalysisofTiimplantsusingX-rayPhotoelectronSpectroscopy(XPS)measurementsrevealedthepresenceofAlandfluoridewhichweredepositedduringthesand-blastingandacidetchingprocess[37].
TheoxidizedstateofAl,(alumina)isconsideredtobestableinphysiologi-calfluidswithveryminortissuereaction.
Therefore,ithasbeenusedasacoatingmaterialtoenhancethecorrosionresistancecharacteristicsofdentalimplants[15].
Inaddi-tion,favourablecellreactionswereobservedforaroughTisurfaceenrichedwithAl,CaandPions,whenincorpo-ratedintotheTisurfaceappearstoimproveviabilityofosteoblasts[22].
SomeTidentalimplantsmaycontainsurfacecontami-nantsthatmaycauseaproblemduringtheosseointegra-tionprocess.
AstudydonebySemezetal.
[38]showedthattheamountofAlinadentalimplantcalledMYIM-PLANT(NobelBiocare,India)was12-foldhigherthanthatfoundinTialloystypicallyusedfordentalimplants(between0andabout0.
06)[38].
Furthermore,anotherstudysuggestedthatahighconcentrationofresidualaluminiumoxide(AlO2)mayinterferenegativelywiththeosseointegrationprocess[39].
2.
8Silicon(Si)SiwasdetectedonthefailedimplantsalongwithP,Ca,Na,S,Cl,Znandcopper(Cu)ontheTisurface.
Ithasbeensuggestedthatthesurfacecontaminantsmayenhancetheinflammatoryresponse,alteringthehealingprocesswhichleadstoalterationoftheoxidelayersurfaceandfailureinreosseointegration.
ThepresenceofSiispossi-blyduetothepassivationprocesswheretheSiwasusedasacoatingorintreatingTisurfaces[36,40].
Otherthanthepassivationprocess,Simaycomefromiondissolutionfromtheglassstoragevialsorprobably(lesslikely)fromrubbergloves.
Itmayalsooriginatefromthefabricationprocess,cleaningandsterilizationprocess,thehandlingenvironmentandstorage(glassvials)andanalysisprepa-rationprocedures[36].
Nevertheless,Siplaysanessentialelementinbonemetabolismincludingpromotingosteoblastdifferen-tiation,stimulationofcollagentypeIsynthesis,allowinghumancelladherenceandmineralizationofhumantis-sue[41,42].
Assuch,SihasbeenusedasacoatingonTidentalimplantsformingaSisol–gelcoatingTi.
AstudydonebyMartnez-Ibanezetal.
[43]showedthattheincor-porationoftetraethylorthosilicate(TEOS)tothesol–gelSicausedhydrolyticdegradationthatleadstoreleasingofSicompoundtothemedia.
ThisresultedinanincreaseintheeffectofosteoinductivepropertiesallowingfordirectcontactbetweennewboneandtheTiimplant[43].
Silicon-basedcoatingshavepropertiesinpreventingbac-terialinfectionpost-implantationandthereforeimprovedpatientoutcomes[44].
2.
9Zinc(Zn)DentalimplantsmadeofZnwerereportedtocauseden-talmetalallergyinJapan[45].
SomeofthetracesofZnioncanbefoundasthismetalisaddedtotoothpasteandmouthwashsolutionsasanti-plaqueagents.
Thisactiv-ityisbelievedtobeduetoretentionin'oralmicroreser-voirs'suchassoftoraltissues,toothsurfacesandbacterialplaque[40].
Nevertheless,Znhasbeenrecognizedasanimportanttraceelementinincreasingthecellproliferationinosteoblasts,boneformationandbiomineralization.
Inaddition,Znhasantibacterialpropertiestherefore,attract-ingresearcherstoincorporatetheZnintoTisurfacesindentalimplantstoenhancebioactivity.
Co-implantedZnandMgionsintoTiimplantsshowedgoodosteoin-ductivity,pro-angiogenicandbacterialeffectswhichcanenhancerapidosseointegration[1,46].
2.
10Fluorine(F)TracesofFandScanbefoundduringtheacid-etchingpro-cess[40].
Fluorideions(upto0.
1wt%)canalsobefoundincommercialtoothpaste,mouthwashsolutionsandpro-phylacticgels.
Itsfunctionsaretopreventdevelopmentofdentalcariesandtoalleviatedentalsensitivity.
How-ever,highconcentrationsoffluorideionsexhibitnegativeeffectsontheprotectiveoxidelayerofTianditsalloys,triggeringlocalizedcorrosivedegradation.
ThedegreeofcorrosionofTianditsalloysaredependsontheconcentra-tionoffluorideionsandthepHofthefluoride-containingenvironments[14,17,47].
Besides,ataconcentrationsof3ppmoffluorideions,Tialloybecomesdiscolouredandataconcentrationabove20ppm,theprotectiveoxidelayerbecomesdegraded[47].
DiscolorationofTiimplantscanbeobservedafterundergoingautoclavingduetoFcon-tamination[48].
2.
11Hydrogen(H)Anacidetchingtechniqueispopularlyusedbymanufac-turerstotexturethesurfaceofdentalimplants.
Combi-nationofacidssuchashydrofluoricacid-nitricacidareoftenusedtoremovetheoxidelayerofTisurfaces.
InthehydrofluoricacidpretreatmentofTisurfaces,theformerattackstheoxidelayerandreactswithTitoformsolubleTifluoridesandH.
WhenthefreeHissaturated,titaniumSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4ReviewPaperhydrideisformed.
ThetitaniumhydridecandramaticallyaffectthemechanicalpropertiesofTiwhichcauseembrit-tlementofthesurfacelayer.
However,byaddingnitricacid,itcanreducefreeHformation[13,49].
AstudyonthefracturesurfaceofretrievedTiscrewthreadsrevealedahighamountofHabsorptionfrombiologicalenvironmentoforalcavitytocausedelayedfractureofaTiimplant[50].
AsynergisticroleofSiandHcoatingimprovestheirinteractionwithosteoblasts.
AstudydonebyMussanoetal.
[51]revealedthathydrogen-richfilmsincreasedkeratinocytesadhesionandviabilitythusenhancingosseointegration.
3Organiccontaminants3.
1HydrocarbonsThecontaminationofTiimplantsurfacestakesonly4weeksforthefreshlycutorpreviouslyphoto-function-alizedimplantstobecoveredwithhydrocarbonsnomat-terthetypeofsurfacetreatmenttheyhaveundergone[37].
ThepresenceofhydrocarbonontheTisurfacemaylessenosteoblastattachmentasthecelladhesionproteincannotattachtosuchsites[52].
Moreover,hydrocarbonfoundintheair,water,orcleaningfluidcanbecontinu-ouslyadsorbedontotheTisurfaceandsignificantlyreducethehydrophilicityofTiduringstorage[53].
Photo-func-tionalizationhasproventobeavalidmethodtoreducetheamountofhydrocarboncontaminationonTidentalimplantsandimproveosseointegration[37].
3.
2CarboxylatesCarboxylatescanbefoundfromthecoatingofTisurfaces.
Carboxylatedmulti-walledcarbonnanotubecoatedTihasbeenshowntohaveincreasedosteoblastproliferation,differentiation,andmatrixmineralization[54].
However,carboxylatescontaminantscancauseadverseeffectsonTisurface.
Highamountsofcarboxylgroupsfromcarbox-ylatesandhydrocarboncanincreasethe(super)hydro-philicityofTi.
Thissubsequentlydecreasethebondingwiththeoxide,N,andSatomsonproteinandreducetheattachmentofcells.
Inordertoremovethecarboxylatecontaminant,high-energyphotonssuchasnon-thermalplasmaandUVlightarerequiredtobreaktheweakbondsbetweencarboxylgroupsandTi[31].
3.
3SaltsoforganicacidsTheproductionoforganicacidscomefromthepro-cessofglycolysisbybacteriaandmayreducepHtocreateafavourableenvironmentforaerobicbacteria.
Accumulationoforganicacidsleadstoanacidicenvi-ronmentandinducescorrosionanddiscolourationofTiimplants[55].
3.
4NitrogenfromammoniumresiduesPresenceofsubstances,likeN,C,O,Ca,andP,foundonthesurfaceoftheTihealingabutmentsformawhiteresidue.
ThesewhiteresiduescauseobstructionontheTisurface.
TheexistenceofNandotherelementsresiduemaycomefrombacterialplaque,bolus,soft-tissueorproteincom-poundsinsalivathathaveadheredtotheTisurface[2].
Inaddition,bacterialbiofilmincreasedthepercentageofbothcarbonandnitrogenontheTisurface.
ByusingH2O2photolysis,thedegradedbiocompatibilityofbiofilm-con-taminatedTisurfacescanberecoveredandmayhavethepotentialforimprovingperi-implantitis[52].
Astudyreportedthatthemicrowave-assisteddryingofHA(hydroxyapatite)sampleswerefoundtobeeffectiveininhibitingthegrowthofEscherichiacoli.
Theformationofammoniumnitrateduringthedryingprocesswhencal-ciumnitrateandammoniawereaddedintothesolutionforTiO2synthesis.
Theresultant,ammoniumnitrate,actsasanoxidantforthecombustionreaction[56].
3.
5BacteriaBacterialcolonizationcandamagethesurfaceTiO2layer.
Astudyreportedthatthecolonizationofbacteriademon-stratesmoreprominentdamageonthesurfacemorphol-ogyandchemistryofimplantsurfaces[57].
Bacteriacancausemicrobialcorrosionwheretheacidicwasteproductscreatedbymicrobesgenerateanacidicenvironment.
Thecorrosionmayleadtoinflammationandoccurrenceofperi-implantitis.
Theseverityofmicrobialcorrosioncanbereducedbyusingantibioticspraysanddipstominimizemicrobepopulations[14,17].
Bacterialcontaminationcanoccurondentalimplantsduringsurgeryandaffecttheosseointegrationandtheprognosisinaclinicallysig-nificantway;howeverscientificevidenceinasystematicreviewconcerningthisisinsufficient[58].
Combinedusageofantisepticssuchaschlorhexidinedigluconate(CHX)orhydrogenperoxideH2O2andpho-todynamictherapy(PDT)wasmoreeffectiveineliminat-ingbacteriabiofilm.
ThiswassupportedbyastudywherethecombinationofantisepticsandPDTshowedeffectivedecontaminationabilityineradicatingStaphylococcusaureusbiofilmfromTisurfaces[59].
Despiteawiderangeoforganicandinorganicimpu-ritiesthatmaycontaminatedentalimplantsurfaces,the10yearclinicalsurvivalrateofthemostcommonlyusedoralimplantsisintherangeof90–95%andtheresultsofReviewPaperSNAppliedSciences(2020)2:1011|https://doi.
org/10.
1007/s42452-020-2810-4"modern,moderatelyroughoralimplantsarebetween95and99%at10years.
[60].
4ConclusionThisreviewistargetedatbothmanufacturersandclini-cians.
Contaminationsofdentalimplantsareintimatelyassociatedwithimplantfailures.
Fromthesummariza-tionofthereview(seeTable1),thecontaminantsmaybecomebeneficialand/orproducedisastrouseffectsondentalimplants.
Thesemayalterthesurfaceenergy,chemicalpurity,thicknessandcompositionoftheoxidelayer.
ItisalsoknownthatthemostcommonelementalcontaminationofTisurfaces,potentiallylinkedtoimplantfailuresaretraceelementssuchasN,Ca,P,Cl,S,Na,SiandF,someorganiccarbonsandbacterialcells/by-products.
However,someofthecontaminantssuchasSiandParebeneficialtothedentalimplantsthatpromoteosseointe-gration.
Thetracesoforganicandinorganiccontaminantscanbefoundfromtheimplantcleaningprocess,Tisurfacetreatmentsuchasacid-etchingandsand-blasting,biologi-calenvironmentandalsothesurroundingenvironment.
Variousmethodsofremovingcontaminantsarealsointro-ducedwiththehopeofpromotingosseointegration.
AcknowledgementsThisstudyissupportedbytheUniversityResearchCouncilunderUniversitiBruneiDarussalamwiththeGrantNumberUBD/RSCH/URC/RG(b)/2018/004,ledbyDrJagjitSinghDhaliwal(PrincipalInvestigator).
CompliancewithethicalstandardsConflictofinterestTheauthorsdeclarethattheyhavenoconflictofinterest.
OpenAccessThisarticleislicensedunderaCreativeCommonsAttri-bution4.
0InternationalLicense,whichpermitsuse,sharing,adap-tation,distributionandreproductioninanymediumorformat,aslongasyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinktotheCreativeCommonslicence,andindicateifchangesweremade.
Theimagesorotherthirdpartymaterialinthisarticleareincludedinthearticle'sCreativeCommonslicence,unlessindicatedotherwiseinacreditlinetothematerial.
Ifmaterialisnotincludedinthearticle'sCreativeCommonslicenceandyourintendeduseisnotpermittedbystatutoryregulationorexceedsthepermitteduse,youwillneedtoobtainpermissiondirectlyfromthecopyrightholder.
Toviewacopyofthislicence,visithttp://creativecommons.
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