Table Of ContentTissueEngineeringforArtificialOrgans
Tissue Engineering for Artificial Organs
RegenerativeMedicine,SmartDiagnosticsandPersonalized
Medicine
EditedbyAnwarulHasan
Volume1
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ContentstoVolume1
ListofContributors xiii
Foreword xxiii
Preface xxv
PartI Fundamentals 1
1 IntroductiontoTissueEngineering 3
RamiMhannaandAnwarulHasan
1.1 Introduction 3
1.2 ClinicalNeedforTissueEngineeringandRegenerative
Medicine 4
1.3 HistoryofTissueEngineeringandRegenerative
Medicine 5
1.4 FundamentalsofTissueEngineeringandRegenerative
Medicine 6
1.4.1 TissueEngineeringversusRegenerativeMedicine 6
1.4.2 TheTriadofTissueEngineering 7
1.4.3 ApproachesinTissueEngineering 8
1.4.4 RecentAdvancesinTissueEngineering 10
1.4.4.1 AdvancesinCellSourcingandCellManipulation 10
1.4.4.2 AdvancesinBiomaterialsandScaffoldProduction 10
1.4.4.3 AdvancesinCellSignalingResearchandBioreactor
Development 11
1.4.4.4 EngineeringComplexTissuesandOrgans 13
1.5 ApplicationsofTissueEngineering 14
1.5.1 ImplantableTissuesandOrgans 15
1.5.2 InVitroModelsforDiseaseStudies 19
1.5.3 SmartDiagnosisandPersonalizedMedicine 20
1.6 ChallengesinTissueEngineering 21
1.7 TheFutureofTissueEngineering 22
1.8 Conclusions 23
References 24
vi Contents
2 BiomaterialsinTissueEngineering 35
SamadAhadian,RahafRahal,JavierRamón-Azcón,RaquelObregón,and
AnwarulHasan
2.1 Introduction 35
2.2 Biomaterial–TissueInteractions 37
2.3 PropertiesofBiomaterials 40
2.4 ScaffoldRequirementsforSpecificTissues 44
2.5 ClassificationofBiomaterials 45
2.5.1 NaturalBiomaterials 45
2.5.1.1 Collagen 45
2.5.1.2 HyaluronicAcid 47
2.5.1.3 AlginicAcid(Alginate) 50
2.5.1.4 Chitosan 51
2.5.1.5 Gelatin 52
2.5.1.6 Fibrin 53
2.5.1.7 Silk 53
2.5.1.8 Peptides 54
2.5.1.9 Elastin 55
2.5.2 SyntheticBiomaterials 55
2.5.2.1 Poly(N-isopropylacrylamide) 55
2.5.2.2 Poly(lacticacid) 57
2.5.2.3 Poly(lacticacid-co-glycolicacid) 57
2.5.2.4 Poly(𝜀-caprolactone) 58
2.5.2.5 Poly(ethyleneglycol) 60
2.5.2.6 Poly(vinylalcohol) 61
2.6 FabricationMethodsofBiomaterials 61
2.6.1 ConventionalFabricationMethods 61
2.6.2 AdvancedFabricationMethods 61
2.6.2.1 Electrospinning 63
2.6.2.2 RapidPrototyping 64
2.7 TestingofBiomaterials 64
2.8 ChallengesforBiomaterialsinTissueEngineering 65
2.9 ConclusionsandFutureDirections 67
Acknowledgment 69
Abbreviations 69
References 70
3 HarnessingthePotentialofStemCellsfromDifferent
SourcesforTissueEngineering 85
DivyaMurali,KunalG.Kshirsagar,AnwarulHasan,and
ArghyaPaul
3.1 Introduction 85
3.2 StemCellsinTissueEngineering 86
3.3 UniqueProperties 86
3.4 TypesofStemCells 87
3.4.1 EmbryonicStemCells 87
3.4.2 InducedPluripotentStemCells 89
Contents vii
3.4.3 AdultStemCells 90
3.4.3.1 MesenchymalStemCell 91
3.4.3.2 HematopoieticStemCells 91
3.4.3.3 Wharton’sJellyStemCells 92
3.5 ApplicationofStemCellsinTissueEngineering 92
3.5.1 BoneTissueEngineering 92
3.5.2 CartilageTissueEngineering 96
3.5.3 CardiacTissueEngineering 97
3.5.4 NeuralTissueEngineering 97
3.5.5 TissueEngineeringforOtherTissuesIncludingSkin,Liver,Lungs,
Bladder,andPancreas 99
3.6 ChallengesandFutureDirections 101
3.7 Conclusion 102
Acknowledgments 102
References 102
4 InducedPluripotentStemCellsinScaffold-BasedTissue
Engineering 111
DeeptiRana,MinalThacker,MariaLeena,andMuruganRamalingam
4.1 Introduction 111
4.2 BasicsofInducedPluripotentStemCells 112
4.3 ConceptofScaffold-BasedTissueEngineering 116
4.4 Cell–ScaffoldInteractions 118
4.5 ApplicationofInducedPluripotentStemCells 121
4.5.1 BoneTissueEngineering 121
4.5.2 CartilageTissueEngineering 125
4.5.3 CardiacTissueEngineering 127
4.5.4 SkinTissueEngineering 131
4.5.5 NeuralTissueEngineering 132
4.6 ConcludingRemarks 134
Acknowledgments 134
References 134
5 BiosensorsforOptimalTissueEngineering:Recent
DevelopmentsandShapingtheFuture 143
JihaneAbouzeid,GhinwaDarwish,andPierreKaram
5.1 Introduction 143
5.2 FundamentalsofBiosensors 143
5.3 BiosensingTechniques 145
5.3.1 SpectroscopicTools 145
5.3.1.1 ColorimetryUsingGoldNanoparticles 145
5.3.1.2 FluorescenceSpectroscopy 146
5.3.2 ElectrochemicalMethods 146
5.4 Real-TimeSensinginTissueEngineeringandCell
Growth 147
5.4.1 Metabolites 147
viii Contents
5.4.2 OxygenMonitoringDuringCellGrowth 148
5.4.3 ReactiveOxygenSpecies 149
5.4.4 CellAdhesion 150
5.4.5 NanowireField-EffectTransistors 150
5.4.5.1 IntroductiontoField-EffectTransistors 150
5.4.5.2 Field-EffectTransistorsforIntracellularMonitoring 151
5.4.6 Microfluidics-BasedBiosensors 153
5.4.6.1 MicrofluidicChips 154
5.4.6.2 Microfluidics-IntegratedTissueScaffold 155
5.5 InVivoImplementationsandtheChallengesFaced 155
5.5.1 AntifoulingCoatings 156
5.5.2 NitricOxide 157
5.5.3 TemplatedPorousScaffolds 157
5.6 ConclusionandFutureDirections 158
References 159
6 BioreactorsinTissueEngineering 169
RaquelObregón,JavierRamón-Azcón,andSamadAhadian
6.1 Introduction 169
6.2 Bioreactors 170
6.2.1 SpinnerFlasks 171
6.2.2 Rotating-WallVesselBioreactors 172
6.2.3 WaveBioreactors 173
6.2.4 PerfusionBioreactors 173
6.2.4.1 Parallel-PlateBioreactors 173
6.2.4.2 Hollow-FiberBioreactors 173
6.2.4.3 Fixed(Packed)andFluidized-BedBioreactors 174
6.2.5 MicrofluidicBioreactors 174
6.3 ApplicationsofBioreactorsinTissueEngineering 175
6.3.1 BioreactorsforLiverTissueEngineering 176
6.3.1.1 SpinnerFlasks 176
6.3.1.2 Rotating-WallVesselBioreactors 176
6.3.1.3 PerfusionBioreactors 177
6.3.2 BioreactorsforMusculoskeletalTissueEngineering 179
6.3.2.1 Rotating-WallVesselBioreactors 179
6.3.2.2 SpinnerFlasks 182
6.3.2.3 PerfusionBioreactors 183
6.3.3 BioreactorsforNeuralTissueEngineering 185
6.3.4 BioreactorsforCardiovascularTissueEngineering 187
6.3.5 BioreactorsforBladder,Uterine,andCorneaTissue
Engineering 189
6.4 SummaryandFuturePerspectives 191
Acknowledgment 191
Abbreviations 191
References 192
Contents ix
PartII Applications 215
7 Tissue-EngineeredHumanSkinEquivalentsandTheir
ApplicationsinWoundHealing 217
LaraYildirimer,DiviaHobson,ZhiYuan(William)Lin,WenguoCui,and
XinZhao
7.1 Introduction 217
7.2 DevelopmentofTissue-EngineeredHumanSkinEquivalents 220
7.2.1 EpidermalModels 220
7.2.2 DermalModels 221
7.2.3 BilayeredModels 221
7.2.4 MultifunctionalSkinModels 223
7.3 ApplicationofTESsinWoundHealing 226
7.3.1 ClinicalWound-HealingApplications 226
7.3.1.1 EpidermalSkinRegeneration 226
7.3.1.2 DermalSubstitutes 227
7.3.1.3 Dermo-EpidermalSkinSubstitutes 228
7.3.2 InvivoWound-HealingApplications 230
7.3.3 InvitroWound-HealingModels 231
7.4 ConclusionsandFutureDirections 233
Acknowledgments 234
References 234
8 ArticularCartilageTissueEngineering 243
JiayinFu,PengfeiHe,andDong-AnWang
8.1 Introduction 243
8.1.1 ArticularCartilageCompositionandStructure 243
8.1.2 ArticularCartilageFunction 244
8.2 ArticularCartilageLesionsandRepair 245
8.2.1 ArticularCartilageLesions 245
8.2.2 CurrentTreatmentsinArticularCartilageRepair 246
8.2.2.1 Bone-Marrow-Simulation-BasedTechniques 246
8.2.2.2 OsteochondralTransplantationTechniques 246
8.2.2.3 Cell-BasedTechniques 247
8.2.2.4 TissueEngineering 247
8.3 BasicsofArticularCartilageTissueEngineering 248
8.3.1 Cells 248
8.3.1.1 Chondrocytes 249
8.3.1.2 MesenchymalStemCells 249
8.3.1.3 PluripotentStemCells 251
8.3.2 Scaffold 253
8.3.2.1 DesiredPropertiesforScaffolds 253
8.3.2.2 Classification 254
8.3.3 BiochemicalStimuli 262
8.3.3.1 GrowthFactors 262
8.3.3.2 OtherBioactiveReagents 263
8.3.4 MechanicalStimuli 264
x Contents
8.4 StrategiesinCurrentCartilageTissueEngineering 265
8.4.1 ControlledDeliveryofBiochemicalFactors 265
8.4.2 CombinationTissueEngineeringwithGeneTherapy 266
8.4.3 BiomimeticHierarchicalCartilageTissueEngineering 268
8.4.4 ApplicationofCartilage-ECM-DerivedScaffolds 269
8.4.5 Scaffold-FreeCartilageTissueEngineering 270
8.4.6 HomingEndogenousCellsforCartilageRegeneration 271
8.5 ConclusionsandFutureDirections 273
ListofAbbreviations 275
References 276
9 LiverTissueEngineering 297
JessicaL.Sparks
9.1 Introduction 297
9.2 LiverBiology 299
9.2.1 Organ-ScaleAnatomy 299
9.2.2 HistologicalStructure 300
9.2.3 CellTypesoftheLiver 302
9.2.4 LiverExtracellularMatrix 303
9.3 LiverBiomechanics 304
9.3.1 LiverBiomechanicalProperties 304
9.3.2 LiverHemodynamics 307
9.4 LiverMechanobiology 308
9.4.1 Cellular-ScaleMechanicalForces 308
9.4.2 CellularMechanotransductionMechanisms 309
9.4.3 MechanosensitivityofLiverCellTypes 310
9.5 BiophysicalStimuliinLiverTissueEngineeringScaffolds 313
9.6 ConclusionandFutureDirections 314
References 314
10 DevelopmentofTissue-EngineeredBloodVessels 325
HaiyanLi
10.1 Introduction 325
10.2 BiologyofBloodVessels 326
10.2.1 StructureandComponentofNativeBloodVessels 326
10.2.2 FunctionsofNativeBloodVessels 326
10.2.3 VasculogenesisandAngiogenesis 329
10.3 TissueEngineeringofBloodVessels 329
10.3.1 TissueEngineeringofMicrovascularNetworks 329
10.3.1.1 Prevascularization-BasedTechniques 329
10.3.1.2 Vasculogenesis-andAngiogenesis-BasedTechniques 332
10.3.2 StrategiesforEngineeringVascularReplacementGrafts 340
10.3.2.1 MaterialSelection 340
10.3.2.2 TubularScaffoldFabrication 342
10.4 ConclusionandPerspective 344
Acknowledgment 345
References 345
Contents xi
ContentstoVolume2
Foreword xv
Preface xvii
11 EngineeringTracheaandLarynx 363
MartaB.Evangelista,SaitCiftci,PeterMilad,EmmanuelMartinod,
AgnesDupret-Bories,ChristianDebry,andNihalE.Vrana
12 PulmonaryTissueEngineering 389
PatrickA.LinkandRebeccaL.Heise
13 CardiacTissueEngineering 413
EunJungLeeandPamelaHitscherich
14 ApproachesandRecentAdvancesinHeartValveTissue
Engineering 445
AnnaMallone,BenediktWeber,andSimonP.Hoerstrup
15 MusculoskeletalTissueEngineering:Tendon,Ligament,
andSkeletalMuscleReplacementandRepair 465
JorgeA.Uquillas,SettimioPacelli,ShuichiroKobayashi,and
SebastiánUquillas
16 BoneTissueEngineering:StateoftheArt,Challenges,and
Prospects 525
JanO.Gordeladze,HåvardJ.Haugen,StåleP.Lyngstadaas,and
JanneE.Reseland
17 TissueEngineeringofthePancreas 553
MasayukiShimoda
18 TissueEngineeringofRenalTissue(Kidney) 575
RaquelRodrigues-Díez,ValentinaBenedetti,GiuseppeRemuzzi,and
ChristodoulosXinaris
19 DesignandEngineeringofNeuralTissues 603
MuhammadN.HasanandUmutA.Gurkan
20 Neural-TissueEngineeringInterventionsforTraumatic
BrainInjury 655
TalaElTal,RayanElSibai,StefaniaMondello,andFirasKobeissy
21 BionicsinTissueEngineering 677
ThanhD.NguyenandBrianP.Timko
Index 701
