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Nanobiomaterials in Clinical Dentistry - City University of
CHAPTER 2 Nanotechnology and Nanobiomaterials in Dentistry 17 Seyed Shahabeddin Mirsasaani, Mehran Hemati, Tina Tavasoli, Ehsan Sadeghian Dehkord, Golnaz Talebian Yazdi and Danesh Arshadi Poshtiri
Chapter 9 Emerging Polymers in Dentistry - Bertassoni lab
F Puoci (ed ), Advanced Polymers in Medicine, DOI 10 1007/978-3-319-12478-0_9 Abstract Polymers represent the foundation of modern restorative Dentistry The majority of dental procedures currently utilized in clinical dentistry depend on the close interaction of polymeric materials with dental tissues In fact, the den-
HITT 1211 Chapter 9 Lecture Notes Information Technology in
Chapter 9 Lecture Notes Information Technology in Dentistry Dental informatics—combines the use of computers with dentistry • Eighty-five percent of dental offices make some use of computers Special purpose applications: education • Computer-generated treatment plans to educate patients • Simulations for training dentists
Nanobiomaterials in Clinical Dentistry - cityueduhk
CHAPTER 2 Nanotechnology and Nanobiomaterials in Dentistry 17 Seyed Shahabeddin Mirsasaani, Mehran Hemati, Tina Tavasoli, Ehsan Sadeghian Dehkord, Golnaz Talebian Yazdi and Danesh Arshadi Poshtiri
TITLE 37 PROFESSIONS AND OCCUPATIONS CHAPTER 9 DENTISTS Section
dentistry or dental hygiene A Any health care provider possessing a degree in dentistry or a dental degree as specifically approved under R S 37:771 and a medical degree must be licensed and maintain licensure with the Louisiana State Board of Dentistry prior to and as long as said health care provider practices, engages in,
53343_713_26.pdf Nanobiomaterials in
Clinical Dentistry
Edited by
Karthikeyan Subramani
Waqar Ahmed
James K.Hartsfield, Jr.
AMSTERDAMBOSTONHEIDELBERGLONDON
NEW YORKOXFORDPARISSAN DIEGO
SAN FRANCISCOSINGAPORESYDNEYTOKYO
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Contents
Forewordby Professor C.N.R.Rao....... .............................................. ....................................xvii
Forewordby Professor PeixuanGuo .................................................. ..................................... xix
Acknowledgments.................................................................................................................xxi
SECTION 1INTRODUCTION
CHAPTER1 Introduction toNanotechnology ..................... ...................................................... 3
Waqar Ahmed,Abdelbary ElhissiandKarthikeyan Subramani1.1 Introduction.....................................................................................................3
1.2 Approachesto nanotechnology .......................................................................4
1.3 Nanotechnologyona large scaleand volume................................................5
1.3.1 Top-downapproach ...................................................................................5
1.3.2 Bottom-upapproach ................................................................. .................6
1.4 Applications........... .......................................................................................11
1.5 Futureconside rations....................................................................................15
1.6 Nanobiomaterialsinclinical dentistry................... ....................................... 15
References..............................................................................................................16
CHAPTER2 Nanotechnol ogyandNanobiomaterialsin Dentistry.............. ...............................17
Seyed ShahabeddinMirsasaani, MehranHemati, TinaTavasol i, Ehsan SadeghianDehkord, GolnazTalebian Yazdi andDaneshArshadiPoshtiri2.1 Introduction...................................................................................................17
2.2 Nanoscalemateri als............................................................................. .........18
2.2.1 Nanoparticles.................................. .........................................................20
2.2.2 Characterization.......................................................................................20
2.2.3 Nanofibers................................................................................................21
2.3 Nanodentistry......... .......................................................................................21
2.4 Nanobiomaterialsindentistry .............................................................. .........21
2.5 Nanobiomaterialsinprev entivedentistry .....................................................22
2.6 Nanobiomaterialsinrestorative dentistry..................... ................................ 25
2.6.1 Dentalnanocompo sites............................................................................25
2.6.2 Silvernanoparticles inrestorative dentalmaterials ................................ 29
2.7 Nanocompositesinbone regeneration ................................................. .........29
2.8 Conclusions...................................................................................................30
References..............................................................................................................30
v SECTION 2NANOSCALE MATERIALSAND THEIRAPPLICATIONSIN DENTALBIOMATERIALS
CHAPTER3 CarbonNanotube-Bas edMaterial sPreparation, Biocompatibility,and Applications inDentistry.............. ..................... ................37Mrinal BhattacharyaandW ook-JinSeong
3.1 Introduction...................................................................................................37
3.2 Preparationof CNTcomposites ............................................... .....................38
3.2.1 Meltprocessing ofCNT composites...................... .................................40
3.2.2 Solutionprocessing ofCNT composites............................... ..................42
3.2.3 Insitu polymerizationtechnique ............................................................. 42
3.2.4 Electrospinning........................................................................................43
3.2.5 Layer-by-layerassembly .............................................................. ...........46
3.3 Conductivity..................................................................................................47
3.4 CNTcytotoxicity ...........................................................................................48
3.5 CNTapplications indentistry ......................................... ..............................50
3.5.1 Dentalrestorative materials............................ .........................................50
3.5.2 Bonydefect replacementtherapy ............................................................ 52
3.5.3 Protein,gene, anddrug delivery............................ .................................54
3.6 Summaryand conclusions................................ ............................................ 56
References..............................................................................................................56
CHAPTER4 Dentaland SkeletalAp plicationsof Silica-BasedNanom aterials......................... 69 Shin-Woo Ha,M. NealeWeitzmann andGeorge R.Bec kJr .4.1 Introduction...................................................................................................70
4.2 Silicananoparticles .......................................................................................70
4.3 Synthesisof silica-basednanomaterial s........... ............................................71
4.3.1 Methods....................................................................................................72
4.3.2 Dispersibilityandpurification .............................................................. ...73
4.3.3 Compositesand functionalization...................... .....................................74
4.4 Physicochemicalproperties ofsilica-based nanomaterials .......................... 75
4.4.1 Size...........................................................................................................75
4.4.2 Shape........................................................................................................76
4.4.3 Surfaceproperties andmodifications ...................................................... 77
4.5 Dentalapplications ofsilica- basednanomaterials .......................................78
4.5.1 Compositeresins ......................................................................................78
4.5.2 Surfacetopography: roughness,polishing, and
antimicrobialproperties ...........................................................................82
4.6 Skeletalapplic ationsofsilica-based nanomaterials .....................................83
4.6.1 Skeletalmodeling andremodeling, osteoblast,and osteoclasts............. 83
4.6.2 Silicaand osteoblasts............................... ................................................84
4.6.3 Silicananoparticles andbone metabolism............................ ..................84
4.6.4 Osseointegration.................................................................... ..................85
4.6.5 Biocompatibility/toxicology....................................................................85viContents
4.7 Conclusions...................................................................................................85
Acknowledgments................... ..............................................................................86
References..............................................................................................................86
CHAPTER5 Nanoparticles ,Properties,andApplications inGlassIonomerCemen ts.............. ..93Abdul SamadKhan ,MariaKhan andIhtesham UrRehman
5.1 Introduction...................................................................................................93
5.2 Smartdental materials........... .............................................................. .........94
5.3 Nanotechnologyanddentistry ............................................. .........................94
5.4 Glassionomer cement................... ................................................................95
5.5 ModifiedGIC ................................................................................................97
5.6 Resin-modifiednano-glass ionomercomposites.......................................... 98
5.7 Nanoparticles-basedGIC.............................. ..............................................103
5.8 Conclusions.................................................................................................105
References............................................................................................................106
CHAPTER6 Nanostructured DentalCompositesand Adhesiveswith Antibacterialand Remineralizing CapabilitiesforCari esInhibition.............. ......109 HockinH.K. Xu,Lei Cheng, KeZha ng,MaryAnne S.Melo, Michael D.Weir ,JosephM.Antonucci ,Nancy J.Lin, ShengLin-Gibson,Laurence C.Cho wandXuedong Zhou
6.1 Introduction.................................................................................................109
6.2 Developmentof antibacterial nanocompositewith
CaP nanoparticles........................................................................................111
6.3 Durabilityof antibacterial nanocompositeinwater-aging ......................... 114
6.4 Antibacterialdentin primer........... ..............................................................118
6.5 Antibacterialadhesi ve.................................................................................120
6.6 Antibacterialand remineralizingadhesive containing NACP................... 123
6.7 Summaryand conclusions..................... ..................................................... 125
Acknowledgments................... ............................................................................126
Disclaimer............................................................................................................126
References............................................................................................................126
CHAPTER7 Nanotechnol ogyandNanoparticlesinContempor aryDental Adhesives............... 131MohammadNas sifandFarid ElAskary
7.1 Introduction.................................................................................................132
7.2 Briefhistory ofdental adhesives........... ..................................................... 132
7.3 Contemporaryadhesive systems .................................................................133
7.3.1 Etch-and-rinseadhesives............................ ...........................................135
7.3.2 Self-etchingadhesives ...........................................................................135
7.3.3 Glassionomer adhesive...................... ...................................................137
7.4 Chemicalcompositi onsofcontemporaryadhesi ves........... .......................138
7.4.1 Resinmonomers ........................................................ ............................139
7.4.2 Solvents..................................................................................................140viiContents
7.4.3 Fillers............................ .........................................................................140
7.5 Ketacnanopri mer........................................................................................145
7.6 Nanoleakage................................................................................................147
7.7 Atomicforce microscopyin thefield ofdental adhesion..................... .....149
7.8 Howcan nanoscience andnanotechnologyimprovethe outcomeof
clinical adhesivedentistry? .........................................................................151
7.8.1 Useof hydrophobiccoating ................................................................. .151
7.8.2 Extendedpolymerizatio ntime.............................................................. .152
7.8.3 Useof MMPsinhibitors ........................................................ ................152
7.8.4 Improvedimpregnation .................................................................... .....153
7.8.5 Wetethanol bondingapproach .............................................................. 153
7.8.6 Improvingdental collagennetwork mechanicalproperties
prior tobonding .....................................................................................154
7.8.7 Enhancingbiomimetic remineralization............................... ................155
7.9 Futureprospective ofnanotech nologyin thefieldofadhesi ve
dentistry.......................................................................................................155
7.9.1 On-demandantibacterial adhesives............................... ........................155
7.9.2 Improvingadhesive polymerizationthrough catalytic
activity ofnanoparticles ........................................................ ................155
7.9.3 Antibacterialorthodontic adhesivescontaining nanosilver.................. 156
7.9.4 Radiopaquedental adhesives.................................. ...............................156
7.9.5 Self-adhesivecomposites .......................................................................156
7.9.6 Self-healingadhesives ...........................................................................156
7.9.7 High-speedAFM ........................................................... ........................157
7.10 Conclusionsand futuredirections ......................................... ...................159
References............................................................................................................160
SECTION 3NANOBIOMATERIALS INPREVENTIVE
AND RESTORATIVEDENTISTRY
CHAPTER8 Nanobiomater ialsinPreventiveDentistry .................. .......................................167
Matthias Hannigand Christian Hannig
8.1 Introductioncurrentchallengesin preventive dentistry..................... .....167
8.2 Theubiqui tousphenomenonofbioadhes ionon dental hardtissues.........168
8.3 Mainstrategies forimplementa tionof nanosized
materials indental prophylaxis......... ..........................................................170
8.4 Modulationof bioadhesion andbiofilmmana gement................... ............170
8.5 Effectson de-and remineralization......... ................................................... 174
8.6 Erosion.........................................................................................................176
8.7 Nanosizedcalcium fluoride..................... ...................................................177
8.8 Dentinhypers ensitivity...............................................................................177
8.9 Regenerationof dental hardsubstances......................................... ............178
8.10 Discussionand clinicalrecomme ndations............... ...................................179
viiiContents8.11 Conclusions.................................................................................................180
References............................................................................................................181
CHAPTER9 Silverand Phosphate Nanoparticles: AntimicrobialApproachand CariesPreven tionApplication.................. ......................... ........................187
D.B. Barbosa,D.R.Mont eiro,A.S. Takamyia,E.R. Camargo,A.M. Agostinho,A.C. B.DelbemandJ.P .Pessan
9.1 Welcometo nanoworld................. ..............................................................187
9.2 NanoparticlesX BUGS"............. ..............................................................190
9.2.1 Microbialbiofilms andtolerance ........................................................ ..190
9.2.2 Silvernanoparticles andbiofilms ........................................................ ..192
9.3 Phosphatesmicro- andnanopartic lesand cariesprevention...................... 195
9.3.1 De-and remineralizationprocess ........................................................ ..195
9.3.2 Nanophosphatesandmicrobial adhesion......................... .....................195
9.4 Prosand consof nanoparticlestoward biological-dental application .......196
9.4.1 Toxicity..................................................................................................196
9.4.2 Processingcosts .....................................................................................197
9.4.3 Potentialuse indental fieldand futuredirections ................................198
9.5 Conclusions.................................................................................................198
References............................................................................................................199
CHAPTER10 Nanoparticles andtheControl ofOralBiofilms ..................... ..................... ......203
Robert PatrickAllaker
10.1 Introduction...............................................................................................204
10.2 Biofilmsand oralinfections .............................................................. .......205
10.2.1 Formationand propertiesof oralbiofilms ........................................ 205
10.2.2 Oralbiofilms anddisease .................................................................. 206
10.2.3 Controlof oralbiofilms ........................................................ .............207
10.3 Antimicrobialnanopartic lesandoral biofilmcontrol ..............................207
10.3.1 Nanoparticulatemetals asantimicrobial agents................................ 207
10.3.2 Nanoparticulatemetal oxidesas antimicrobialagents ......................211
10.3.3 Oralapplications ofnanoparticulate metalsand metaloxides .........213
10.3.4 Quaternaryammonium compounds.................................. .................215
10.4 Antiadhesivenanoparticlesand oralbiofilm control................. ..............216
10.4.1 Chitosannano- andmicroparticles .................................................... 216
10.4.2 Silicaand siliconnanoparticles ......................................................... 216
10.4.3 Hydroxyapatiteand othercalcium phosphate-based systems........... 217
10.5 Photodynamictherapyand theuse ofnanoparticles
to controloral biofilms............... ..............................................................218
10.6 Biocompatibilityofnanoantimicrobia lswith intheoral cavity...............219
10.7 Conclusions...............................................................................................221
Acknowledgments................... ............................................................................223
References............................................................................................................223
ixContentsSECTION 4NANOBIOMATERIALS INORTHODONTICS
CHAPTER11 Nanotechnol ogyinOrthodontics?1: ThePast, Present,and aPerspecti veoftheFuture ..................... ....................... ......................... 231
KarthikeyanSubram ani,SarandeepHuja,G. Thomas Kluemper ,Lorri MorfordandJame sK. HartsfieldJr.
11.1 Introduction...............................................................................................231
11.2 Nanoindentationand atomicforce microscopystudies onorthodontic
brackets andarchwir es..............................................................................233
11.3 Frictionreducing nanocoatingson orthodontic archwires........... ............234
11.4 Nanoparticlesin orthodonticadhesi ves................. ...................................236
11.5 Nanoparticledelivery fromorthodontic elastomericligatures ................ 241
11.6 Developingand futureapplicati onsof nanotechnologyin
dentistry andorthodontics .........................................................................242
11.6.1 Theuse ofshape-memory polymerin orthodontics......................... 242
11.6.2 BioMEMS/NEMSfor orthodontictooth movement
and maxillaryexpansion ....................................................................24211.6.3 Nanorobotdelivery fororal anesthesiaand improved
oral hygeine........................................................................................244
11.7 Temporaryanchorage devices............... ...................................................244
11.8 Conclusions...............................................................................................245
References............................................................................................................245
CHAPTER12 Nanotechnol ogyinOrthodontics?2: FactsandPossibleFuture Applications ................................................ .........................249
TarekEl-Bialy
12.1 Introduction...............................................................................................249
12.2 Nanoscalein orthodontics............... ..........................................................250
12.3 Nanotechnologyandgene therapyin orthodontics .................................. 251
12.4 Nanofabricatedultrasound devicefor orthodontics ................................. 252
12.5 Nanomechanicalsensors fororthodontic forces
and momentsmeasurement .......................................................................25312.6 Futureapplicati onsofnanotechnologyin orthodontics............... ............255
12.7 Conclusions...............................................................................................256
Acknowledgment.................................................................................................256
References............................................................................................................256
CHAPTER13 Nanoparticle CoatingofOrthodont icAppliancesfor FrictionReduct ion.............259Meir RedlichandResh efT enne
13.1 Introduction...............................................................................................260
13.2 Frictionin orthodontics................... ..........................................................260
13.3 Materialsconside rations:fullerene-likenanop articles.............................263
xContents13.3.1 Prelude:inorganic fullerene-likenanoparticles
of WS 2 and MoS 2 ..............................................................................26313.3.2 Synthesis.............................................................................................264
13.3.3 Self-lubricatingsurfaces ....................................................................265
13.4 Orthodonticapplian cescoatedwith nanoparticles...................................266
13.4.1 Challengesin designingthe experimentalsetup ............................... 266
13.4.2 Coatingprocess andtribological measurements......................... ......267
13.4.3 Coatingadhesion andwear .............................................................. ..268
13.4.4 Invitro frictionforce tests...................... ........................................... 269
13.5 Safety:toxicity andbiocompa tibility......... ..............................................274
13.6 Conclusions:fromthe labto theclinic ............................................. .......276
Acknowledgments................... ............................................................................277
References............................................................................................................277
SECTION 5NANOBIOMATERIALS INPROSTHODONTICS
CHAPTER14 Characterization ofSilverNanoparticles Incorporated Acrylic-Based TissueCo nditionerwithAntimicrobial Effectand Cytocompatibility.............. ....283Ki YoungNamand ChulJae Lee
14.1 Introduction...............................................................................................283
14.2 Preparationand identification ofsilvernanoparticles.............................. 285
14.3 Acrylictissue conditioner combinedwithsilver nanoparticles...............287
14.3.1 Fabricationof Ag
-tissue conditionercomposites ............................28714.3.2 Invitro antimicrobialeffects onS. aureus,
Streptococcus mutans, andC. albicans.............................................28714.3.3 Cytotoxictest onhuman gingivalcell line...................... .................289
14.4 CharacterizationofAg
-tissue conditionercomposites............. ..............28914.4.1 Determinationof elutedAg
1 from thespecimens ........................... 28914.4.2 Microstructureof Ag
-tissue conditionercomposites .......................29114.5 Conclusions...............................................................................................292
References............................................................................................................293
SECTION 6NANOBIOMATERIALS INPERIODONTICS, IMPLANT
DENTISTRY, ANDDENTAL TISSUEENGINEERING
CHAPTER15 Bioactive GlassNanoparticlesfor Periodontal Regenerationand ApplicationsinDe ntistry....... ..................................................................299
SandhraM. Carvalho, AgdaA.R.Oliveira, ElkeM.F .Lemos and MarivaldaM.Perei ra15.1 Introduction...............................................................................................299
15.2 Compositionand synthesisof bioactiveglass nanoparticles ...................300
15.3 Bioactivityof glassnanoparticles ............................................... ..............303
15.4 Bioactiveglass indentistry ......................................... ..............................305
15.5 Bioactiveglass nanoparticles inperiodontalregenera tion....................... 309
xiContents15.6 Bioactiveglass nanocomposites ...............................................................312
15.7 Bioactiveglass nanocomposite applicationsinbone
regeneration anddenta limplants........................................... ...................31415.8 Thefuture ofbioactive glassnanop articlesin dentistry..................... .....315
15.9 Conclusions...............................................................................................317
Acknowledgments..................... ..........................................................................317
References............................................................................................................318
CHAPTER16 Impactof Nanotechnology onDental Implants.................................. ..............323
SandrineLaven us,JulieRoze
´, GuyLou arnandPierre Layrolle
16.1 Introduction...............................................................................................323
16.2 Nanoscalesurface modifications........... ...................................................326
16.3 Interactionsof surfacedenta limplants withblood .................................. 327
16.4 Interactionsbetween surfacesand mesenchymal stemcells........ ............328
16.4.1 Originof mesenchymalstem cells............................ ........................329
16.4.2 Migration,adhesion, andproliferation .............................................. 329
16.4.3 Differentiation....................................................................................329
16.5 Tissueintegrati on......................................................................................330
16.6 Conclusions...............................................................................................332
Acknowledgments..................... ..........................................................................332
References............................................................................................................332
CHAPTER17 Titania NanotubeCoatingson DentalImplantswith Enhanced OsteogenicActivi tyandAnti-Infection Properties....... .....................................337Lingzhou Zhao,KaifuHuo andPaul K.Chu
17.1 Introduction...............................................................................................337
17.2 Fabricationof NTson Ti................................ .......................................... 339
17.3 Factorsinfluencing thebio activityof theNTs........................................ 340
17.3.1 Influenceof sterilizationon thebioactivity ofthe NTs................... 340
17.3.2 Influenceof cellphenotype onthe bioactivityof theNTs ...............342
17.3.3 Influenceof proteinconcentration inculture mediumon
the bioactivityof theNTs ................................................................. .34217.3.4 Influenceof proteindistribution patternon the
bioactivity ofthe NTs...................... ..................................................34417.4 Invitro bioactivityof theNTs andin vivoos seointegration................... 346
17.4.1 Invitro bioactivityof theNTs ........................................................... 346
17.4.2 Invivo osseointegrationof theNTs .................................................. 348
17.5 Drug-loadingNTs forbetter bioactivityand antibacterial properties..... 350
17.6 Conclusions...............................................................................................355
Acknowledgments..................... ..........................................................................355
References............................................................................................................355
xiiContents CHAPTER18 CarbonNanom aterialsfor ImplantDentistryandBo neT issueEngineerin g........ 359 Qing Cai,Karthikey anSubramani,Reji MathewandXiaopingY ang18.1 Introduction...............................................................................................359
18.2 Enhancedfunctions ofosteobla stson carbonnanomaterials...................361
18.3 CNT/CNFapplicationsin dentistry..................... ..................................... 367
18.4 Fabricationof carbonnanomat erials................... .....................................370
18.4.1 Carbonnanotubes (CNTs)...................... ...........................................371
18.4.2 Carbonnanofibers (CNFs)...................... ...........................................371
18.5 Cytotoxicityof carbonnanomaterial s................................ .......................372
18.6 Fabricationof carbonnanomat erialswith
improved osteogenicbioactivity................. ..............................................37418.6.1 Biomineralization...............................................................................374
18.6.2 Solgel/electrospinning.....................................................................376
18.7 Uniqueproperties ofCaP nanoparticles embedded
CNFs forbone tissueengineering ............................................................ 38118.8 Conclusions...............................................................................................383
References............................................................................................................383
CHAPTER19 Nanoceramics forBoneRegeneration inthe OralandCraniomaxillofacialComplex .......................................... ...............................389
R. Dziak,K.Mohan, B.Almagh rabiand Y. Park
19.1 Introduction...............................................................................................389
19.2 Nanoceramicsand bonerepair ................................................... ..............391
19.3 Hydroxyapatite..........................................................................................392
19.4 Nano-HAcollagencomposites ...............................................................397
19.5 Hydrogelsand nano-HA............. ..............................................................397
19.6 Chitosanand nano-bioactiveglass composites................. .......................398
19.7 Nanocalciumsu lfate..................................................................................398
19.8 Conclusions...............................................................................................405
Acknowledgment.................................................................................................406
References............................................................................................................406
CHAPTER20 Biomimetics UsingNanotechnology/Nanopar ticlesin DentalTissueRe generation.................................... .................................................411
ShengbinHuang, Tingting WuandHaiyang Yu
20.1 Introduction...............................................................................................411
20.2 Nanotechnologyforcraniofac ialbone andcartilage
tissue engineering......................................................................................412
20.3 Nanotechnologyforperiodo ntalregeneration ..........................................414
20.4 Nanotechnologyfortooth regeneration............... ..................................... 417
20.4.1 Nanomaterialsin biomimeticenamel regeneration.......................... 417
20.4.2 Nanomaterialin enameland dentineremineralization .....................419
20.4.3 Nanomaterialin dentinpulp complexregeneration ........................421xiiiContents
20.5 Conclusions...............................................................................................423
References............................................................................................................423
SECTION 7NANOBIOMATERIALS INENDODONTICS
CHAPTER21 Scopeof Nanotechnol ogyin Endodontics......................................... ..............431
Sami M.A.Cho gle,BassamM.Kinai aand HaroldE. Goodis21.1 Introduction...............................................................................................432
21.2 Clinicalapplicati ons..................................................................................433
21.2.1 Instrumentmodifications ...................................................................433
21.2.2 Enhancementof canaldisinfection .................................................... 434
21.2.3 Materialmodifications .......................................................................436
21.3 Applicationsfor repair andpulpregeneration............. ............................440
21.4 Repairand regeneration ............................................................................441
21.5 Nanotechnologyapplications forrepairand pulpreg eneration...............442
21.6 Conclusion.................................................................................................444
Acknowledgments..................... ..........................................................................445
References............................................................................................................445
SECTION 8SALIVARY DIAGNOSTICSAND NANOPARTICLES
AS DENTALDRUG DELIVERYSYSTEMS AND
THEIR BIOCOMPATIBILITY/TOXICITY
CHAPTER22 Salivaas anEmer gingBiofluid forClinica lDiagnosisand Applications of MEMS/NEMSinSalivar yDiagnostics ............................................ ..............453ChamindiePunyad eeraandPaul D.Slowey
22.1 Introduction...............................................................................................454
22.1.1 SalivaAmiracle biofluid?............................... ...............................454
22.1.2 Salivaproduction andbimolecular transport............................... .....455
22.2 Salivaas abio fluidfor diseasedetection................................................. 456
22.2.1 Salivadiagnostic assaysin themarket todate .................................. 458
22.2.2 Salivaresearch update......................... .............................................. 462
22.3 Applicationsof salivafor earlydetection ofischemic heart
disease andin headand neckcancers ................................................. .....46322.3.1 SalivaryC-reactive proteinlevels asa proxyto diagnoseischemic
heart disease......................................................................................463
22.3.2 SalivaryDNA methylationas aproxy todiagnose
head andneck cancer.................................. .......................................46322.3.3 Applicationsof MicroElectromechanical Systems(MEMS)/
Nano ElectromechanicalSystems (NEMS)in salivarydiagnostics .46522.4 Futureoutlook andconclusions ............................................. ...................466
Acknowledgments..................... ..........................................................................468
References............................................................................................................468
xivContentsCHAPTER23 Nanoparticles asDentalDrug- DeliverySystems ..................... .........................475
E. Pin
o´n-Segundo,N. Mendoza-M unoz
and D.Quintan ar-Guerrero23.1 Introduction...............................................................................................475
23.2 Definitions.................................................................................................479
23.3 Dentalapplicati onsofnanoparticles.................... ..................................... 482
23.3.1 Polymericnanoparticles .....................................................................484
23.3.2 Nonpolymericnanoparticles ..............................................................489
23.4 Futuretrends ..............................................................................................491
Acknowledgments................... ............................................................................491
References............................................................................................................491
CHAPTER24 Orally DeliveredNanoparti cleDrugDeliverySystems forDental Applicationsand TheirToxi cityon SystemicOrgans....... ....................... ..........497YashwantPathakand CharlesPreuss
24.1 Introduction...............................................................................................497
24.2 Dentalapplicati onsofnanodrug delivery................. ..............................499
24.2.1 Nanoparticulatedrug deliverysystems localanesthesia ...................499
24.2.2 Curingthe hypersensitivityin oraltreatments .................................. 500
24.2.3 Nanoroboticdentifrices ......................................................................500
24.2.4 Dentaldurability andcosmetics applicationsin dentistry................ 501
24.2.5 Nanophasealumina fordental applications......................... .............501
24.2.6 Nanoparticulatedrug deliveryin dentalapplications .......................501
24.2.7 Treatmentof oralcancer usingnanoparticulate drug
delivery system............................... ...................................................502
24.3 Toxicityof nanoparticles..................... .....................................................502
24.3.1 Toxicokinetics....................................................................................503
24.3.2 Acuteand chronictoxicity..................................... ............................504
24.3.3 Genotoxicityand carcinogenicity...................... ................................505
24.3.4 Reproductiveand developmentaltoxicity ......................................... 505
24.4 Conclusions...............................................................................................506
References............................................................................................................506
Index..................................................................................................................................509
xvContentsCHAPTER
17TitaniaNanotube Coatingson
Dental Implantswith Enhanced
Osteogenic Activityand
Anti-Infection Properties
LingzhouZhao
c , KaifuHuo a,b and PaulK. Chu b a School ofMaterials andMetallurgy ,Wuhan UniversityofScienceand Technology,Wuhan, China b Department ofPhysics andMaterials Science,City Universityof HongKong, TatChee Avenue,Kowloon,Hong Kong,China
c Department ofPeriodontology andOral Medicine,School ofStomatology, The FourthMilitary MedicalUniversity, WestChangle Road,Xi'an, ChinaCHAPTEROUTLINE
17.1 Introduction........................................................................
.......................................................33717.2 Fabricationof NTson Ti........................................................................
........................ ............. 33917.3 Factorsinfluencing thebioactivity ofthe NTs........................................................................
...... 34017.3.1 Influenceof sterilizationon thebioactivity ofthe NTs ..............................................340
17.3.2 Influenceof cellphenotype onthe bioactivityof theNT s.......................................... 342
17.3.3 Influenceof proteinconcentration inculture mediumon thebioactivity ofthe NTs ....342
17.3.4 Influenceof proteindistribution patternon thebioactivity ofthe NTs ........................344
17.4 Invitro bioactivityof theNTs andin vivoosseointegration ...........................................................346
17.4.1 Invitro bioactivityof theNT s........................................................................
......... 34617.4.2 Invivo osseointegrationof theNT s........................................................................
. 34817.5 Drug-loadingNTs forbetter bioactivityand antibacterialproperties ..............................................350
17.6 Conclusions........................................................................
.......................................................355 Acknowledgments........................................................................ .......................................................355 References........................................................................ .................................................................35517.1Introduction
Dentalimpla ntsareanideal optionfor peoplein good general oralhealth whohave losta toothor teethdue toperiodo ntaldisease ,aninjury,or someotherreasons. Titanium (Ti)and itsalloys are 337Nanobiomaterials inClinical Dentistry.
©2013 ElsevierInc. Allrights reserved.
widelyused asdent alimp lantmaterialsdueto theirgoodmechanical properties, excellent corrosion resistance,and biocompatibi lity.Thelong-termnormalfunct ionsofdentalimplants arerel atedto their earlyand rigidosseointegr ation.Although thespontaneously formedthin TiO 2 passive layer provides somecorr osionresistanceand biocompatibilityfor theTi implant,itisnotableto induce bone formationeffectively. Providingthatthe naturalextracellular matrix(ECM) hasa hierarchical nanostructure [1], theformat ionofananost ructuredsurface onan implantisagood strategy to achieve enhancedosseo integration.Gritblasting,anodization, acid etching, chemicalgrafting, and ionimplanta tionaresome commontechniq uesusedto modifyTi implantstoenhance bone? implantcontact (BIC)and improve theirclini calperformance.Anod izationis anewlydevel oped method toform anoxide nanotube (NT)coat ingonmetalsincluding Ti [2?5].By adjusting the
anodizationconditions suchas thevoltage andtime, nanoscale properties canbe controlled [2,3]. The nanotubulartopography mimicsthedimensions ofcollage nfibri linbonesto some extent[6] and haselasticit ysimilartothat ofbones [7]. TheNTcoating son Tihavebeenfound tofoster the growth of nanostructuredhydroxyapatite insimulatedbody fluids(SBF) [8,9], enhance ECMsecre- tion, mineralization,andother functionalities of osteoblasts,andeven inducethecommitment of mesenchymalstemcells (MSCs)toward bonelin eagein theabsen ceof extraosteogenicsupple- ments(OS) [2,3,10?12]. Emerginginvivo evidence alsosugges tstheabilityof theNT coatings to enhanceosseointegration [13?16]. Implant-associatedinfectionwhichi sanothe rissueimpairing thenormal functiono fdental implants isusually difficult totreatand sometimes requiresimplantr emovalandr epeatedrevi- sionof su rgeries [17]. Variousmeans such asthorough sterilizationa ndstringentaseptic surgical protocols havebeen proposedtomitigate bacterialcontamination. However, bacterialinvasion usually occursafter surgery, and complicationscana risefrominfe ctionofnea rbyt issuesora hematogenous sourceat alatertime [18]. Infectionsassociated withdentalim plantsa recharacter- ized by bacterialc olonizationandbiofilmform ation onthe implanteddevice andinfectiono fthe adjacent tissues(periimplantit is).Bacteriain the biofilmaref armore resistantto antibi otics resulting inpersist entinfectiondespite aggressiveantibiotictherapy [19]. Ase mergingantibiotic resistance becomesm orecha llenging,developingnovelimp lantsorsurfacemodificationm ethods with dualfunctions ofexcellent bone-bondingability andl ong-lastingantibacterial ability throughapr oce durereadyforindustrialp roduction andclinicalapplication is the needforthe hour inim plantdentistr y. NTs ondent alTiimplantsnot onlyprovide ananotopogr aphicalsurface toinduc ebone forma- tion effectivelybutalso serve asa gooddrugloading anddeliverin gplatfo rmfor varioustarget ed agents toattain extrafunctio ns.Many kindsofagents includingantibac terialagent s,bone growth favoringagent s,andanti-inflammat oryagent shavebeenincorporatedinto NTstoenhance the implantsin clinical applications.Itis ourbeliefthatNTs aremor esuitable forload ingand delivery of theinor ganicagentsthatare stableand havevery loweffect ivedoses. Hence,we haveload ed silver [5], strontium[20], zincand soon intothe NTsto achievelong-te rmfunctions concerning antibac terial abilityandosteogene sisinduction . In thischapter ,wesummarize thelatest progressonTiO 2NT coatingsandreview thefactor s
influencingthe NTbioactivi ty,the effectsofthe NTson bonecellfunctionalitie sin vitro,osseo in- tegrationin vivo,and drugload ingand delivery. Thischapter willnot describeindetail theprepa- ration andmechani smofTiO 2 NT byanodi zationbecausethereare alreadysom ereviews inthe literatureregardi ngthefabrication ofanodi zedNTarrayson Tiimplants .338 CHAPTER17 TitaniaNanotube Coatingson DentalImplants
17.2Fabrication ofNTs onTi
Uniformand highlyordered NTarrays canbe readilyfabricate dby anodization ofa Tifoil in F-containingelectrolyte s.Theas-anodized NTs,which growinsituon theTi substrate, arehighl y orientedperpe ndiculartotheTisurf ace [21]. TheNTsare generally fabricated intheaqueous hydrof luoric acid(HF) electrolyte inatwo-electrode electrochemical cellat aconstantpotential between5 and35 V [4,8,10]. At alow anodization voltageof 5V,themorphol ogyof theanodized film issponge -likewithatypical poresiz eof 25nm. At20 V,hollowand cylindrical tube-like fea- tureswith aninner diameterof 80nm form( Figure17.1 ). Besidesthe HF/H 2O electrolyte,many
otheraqueou selectrolyteshave alsobeendevelopedto fabricate NTs,for example, H 2 SO 4 /NaF/ (A)(B) (C)(D)FIGURE 17.1
(A andB) NTs formedat5and 20V in0.5 wt%aqueous HFsolution withtube diametersof 25and 80nm, respectively.(C andD) NTs formedat 10and40V inan EGsolution with0.5 wt%NH 4 F,5 vol%CH
3OH, and5 vol%H
2O withtube diametersof 30and 80nm, respectively.
Reprintedwith permission fromRef.[4].
33917.2Fabrication ofNT sonTi
H 2O[7], NaH
2 PO 4 /HF[9], andNa 2 SO 4 /HF[9]. Thediamet eroftheNTs canb eregulated tovary from15 to140 nmand theleng thcan rangefrom 200to1000nm byadju stingthe electrolyte con-
tent andanodi zationvoltage [21]. Whenusin gpolarorgan icelectrolytes,muc hlongerNTsof hun- dreds of micrometerscanbe fabricated [22]. Ethyleneglycol (EG)isthecommon lyused organic solv ent tofabric ateNTs.The typicalNTs formedbyanodization ofa Tifoi lin anEG solution with 0.5wt% NH 4F, 5vol% CH
3OH, and5 vol%H
2O at10 Vfor 1h and40 Vfor 40min are
showninFigure 17.1Cand D, respectively.
17.3Factors influencingthe bioactivityof theNTs
Variousfactors caninflue ncethe bioactivityofthe NTsduring theirpreparationand cellcultur e process.A betterunderstan dingof thesefactorshelp sto optimize theNTsforbetter biological performance.Here, wesum marizethe factorssuchas theste rilizationprocess, phenotypeof cells, proteinconcentr ationinthecultur emedium, andsmo othnessofthetop endsof thetube wallsthat affect thebioa ctivityoftheNTs.17.3.1Influence ofsterilization onthe bioactivityof theNTs
Sterilizationprocess isesse ntialfor theinvitrobioa ctivityassay andfin allyin vivoapplications of dentalimplan ts.However,many researcherschoosesterilizat ionmethods arbitrarilywhen study- ing thebiocomp atibilityofNTs.In someexper iments,auto clavingis used[1013,23] , whereasin
someothe rs,ultraviolet(UV) irradiationorethanol immersionis used[2426]. Sterilizationmeth- ods canbe considered asaposttreatme ntof thesample s,andthevarioussterilization methodscan change thesurface properties ofthesamples andcorrespo ndingbioa ctivity.Wehave compared the effectsof three commonlyusedste rilizationmethods, namelyautocla ving,UVirradiation,andeth- anol immersiononthe bioactivity ofNTs. We havefound thatthe sterilizatio nprocess canmodifythesurface ofthe biomaterials. Strong discolo ration ofsamples isoccas ionallyobser vedafterautoclaving, butitisusually notfound after UV oretha nolsterilization. Themostsignificantlymodified characteristic saftersterilization are surface chemistryandwett ability.Autoclavin gdecreasesthe surfacefreeenergy ofbiomedical implants,but contrarily UVtreatmentdramatically enhances thatof Ti(Figure 17.2A). The
decr ease inhydrophil icitybyautoclaving isrelated tothedeposition ofhydrop hobiccontam inants on theimplant surfaces [27]. Theenhanc ementinthesurface freeener gyof Tiby UVtreat mentis assoc iated withthe molecular structurealteration ofsurfacetitaniawith abundantTiOH group formationand removalof surface hydrophobic contaminantsespecia llyhydrocarbons [28,29]. The changesin thesurface properties subsequently leadtodifferential cellresponses. UV andetha nolsterilizations inducehigherinitialadherent cellnumb ers(Figure17.2B ) andcell prolif eration thanauto claving,andUVirradiationlead sto thebest cellfuncti onalitiesincluding adhesion,prolif eration,aswellas differentiation represented byrelated geneexpressions.UV steril- ization appearsto bethe optimalsterilizat ionmethod fromthe viewpointofelimina tingsurface contamination.Oh etal.
[30]have investigatedtheinf luenceof twosterilizationmethods ofwet autoclaving vers us dryautoclavin gonthefunctio nalitiesof osteoblasts culturedonthe NTs.Their results340 CHAPTER17 TitaniaNanotube Coatingson DentalImplants
5 V 20V
Total02040
Surface free energy (mJ/m
2 ) 6080(A)
Polar Dispersive
P 5 V20 V P5 V20 VPAutoclave
UVEthanol
5V20 V
30 min0
Cell number/field
450400
350
* * * *## # ** ********** ****** **** ** **300 250
200
150
100
50(B)
P5V20V
60 minP5V20V
120 minPAutoclave
UVEthanol
FIGURE 17.2
(A) Valuesof surfacefree energy(mJ/m 2 ) and(B) initialosteoblast adhesionof 5V NTs, 20V NTs, andpolished Tiaftersterilized byautoclaving, UVirradiation, andethanol immersion.The samplessterilized by
UV andethanol generatehigher surfacefree energyand thusinitial adherentcell numbers.* p,0.05 and **p,0.01 comparedwith theautoclave-sterilized ofeach surface,# p,0.05 comparedwith theUV-sterilized ofeach surface.
Reprintedwith permission fromRef.[4].
34117.3Factors influencingthe bioactivityof theNT s
indicate thatthe adhesion,prolif eration,and alkalinephosphatas e(ALP) activityofosteoblast s culturedon thelarger 70and 100nm NTsare dramatically changedby thedifferent sterilizatio n conditionsat alow cellseeding densityof 10,000cells/w ellin 12-cellculture well. Thedifferent autoclavingmethods create hugedifferencesin celladher enceon70and 100nm NTscompare dto30 and50 nmNTs. Theseresu ltsreveal thatthe nanofeaturesofprot einsadher edon theNTs can
be alteredby differentsteri lizationmethods .17.3.2Influence ofcell phenotype onthebioactivityof theNTs
NTs havebeen assayed forvariousbiological purposessuch asbone implants[2,3,1012,31], transcu taneous partof theim plants[32], andvascular prostheses[24]. Thereis muchevid ence from the variousprimary cellphenot ypesincludi ngprimaryosteoblasts, osteoblastcelllines, MSCs,endothel ialcells(ECs),vascular smoothmuscle cells(VSMCs) ,dermal fibroblasts, and epidermalkera tinocytessuggestingthat differentcellphenotypes responddif ferentlyto theNTs. We haveobserved differential responsesofprimary ratcalvarial osteoblasts totheNTscompared to thoseofthe osteoblast celllines [10,31]. Our resultsto somedegree corroborate thereport by Brammeret al.[33]. Theyhavecompare dthe effectsofTiO 2 and C-coatedNT surface chemistries on osteoblastandosteop rogenitorcell behaviors.TheTiO 2NT surfaceinduces anincrease inosteo-
blast functionalitiesintermsof ALPact ivity.In contrast, itis thecarbonchemistry thatresu ltsin increasedbone mineral depositionandbone matrixprotein expression ofoste oprogenitorcells. More significantevidenceu nambiguously demonstratingthephenotypicdepend enceofcell responsesto theNTs isobta inedfrom ECs/VSMCs anddermalfibroblasts/epiderm alkeratino cytes.Peng etal.
[24]have foundthat theNTs significantly enhanceEC proliferationbutdecrease VSMC proliferation(
Figure17.3 ). Smithet al.[32]have reportedincreased dermalfibroblastand decr eased epidermalkera tinocyteadhesion,prolifera tion,anddifferentiati onontheNTs. The evidenceremin dsusthatwhen comparing thereports onthe bioactivityoftheNTs from differentsourc es,itshould beborne inmindthatthe responsesof cellsto theNTs arephenotypi c dependent.In addition, thedifferentialrespon seof thedifferentcel lphenotypesto theNTs provides a goodapproach fortissue specific implantsthat selectivelybenefit fromthe desired tissueintegra- tion whilesimul taneouslyinhibitingthe unwantedresponse.17.3.3Influence ofprotein concentrationin culturemedium
on thebioactivity ofthe NTs The proteinsadsorbed tothe implant surfaceplay akeyrolein cell/implant interactions. Wehave comparedthe influence oftheserum concentration inthe culturemedium onthechangein thepro- tein adsorptionamountand theconsequ entinitial cellspreadi ngontheNTs andflat Ti[2]. Diff erent serumconce ntrationsdonotinflue ncecell adhesion onflatTicont roland 25nmNTs but seriouslyaffectthat on80 nmNTs (Figure17.4 ). Thecells attach andspreadwellon the
80nm NTswhe nculturedwith 5%or10%serum while2% serumleads topoor cell adhesion. This phenomenoncanbe explained bythe celladhesion mechanism. Arequire mentfornormalcell functionalitieson biomaterialsisstable adhesionorelsecell apoptosis willoccur [34]. Therefore, the amount ofadsorbed proteins isveryimportant forthe biological performanceofbiomater ials. The amountsof proteins onthenanostructured surfaceincreas ewith serumconcentrationsfrom