Table Of Content3D Cell Culture
Pan Stanford Series on Renewable Energy — Volume 2
3D Cell Culture
Fundamentals and Applications in Tissue
Engineering and Regenerative Medicine
Ranjna C. Dutta | Aroop K. Dutta
editors
Preben Maegaard
Anna Krenz
Wolfgang Palz
The Rise of Modern Wind Energy
Wind Power
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April3,2018 15:5 PSPBook-9inx6in 00-Dutta-and-Dutta-Prelims
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3DCellCulture:FundamentalsandApplicationsinTissue
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ISBN978-981-4774-53-6(Hardcover)
ISBN978-1-315-14682-9(eBook)
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Contents
Preface ix
Acknowledgements xi
Synopsis xiii
1 Introduction 1
1.1 CellCulture:HistoricalPerspective 1
1.2 CellCulture:2Dvs.3D 3
2 SignificanceofTissue-SpecificExtracellular
Microenvironment(ECM) 13
2.1 Introduction 13
2.1.1 WhatIsECM? 15
2.1.2 TissueSpecificityofECM 20
2.1.3 Essential/RepresentativeComponentsofECM 22
2.1.3.1 Collagens(fibrillarandstructural) 27
2.1.3.2 Elastin(elastic) 36
2.1.3.3 Microfibrilassociatedmacromolecules
(fibrillar) 38
2.1.3.4 Laminin(adhesive) 43
2.1.3.5 Fibronectin(adhesive) 45
2.1.3.6 Matricellular(anti-adhesive) 49
2.1.3.7 Matrikinesandmatricryptins 52
2.1.3.8 Proteoglycans 53
2.1.3.9 Glycosaminoglycans(GAGs) 61
2.1.3.10Hyaluronan(hyaluronicacid) 61
2.2 Cell-CellInteraction 64
2.3 Cell-EffecterInteraction 65
2.4 Cell-ECMInteraction 66
2.4.1 ProtrusiveContacts 66
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vi Contents
2.4.2 ContractileContacts 70
2.4.3 MechanicallySupportiveContacts 70
2.5 ECMRelatedDisorders 74
2.6 Conclusion 79
2.6.1 Classification 79
2.6.2 Inter&IntramolecularECMInteractions 80
2.6.3 Implications 81
3 ECMMimickingfor3DCellCulture 103
3.1 3DCellCulture(Introduction) 103
3.1.1 SignificanceofECMMimicking 104
3.1.2 ECMMimicking/Reconstitution 107
3.1.2.1 Physicalmimicking 108
3.1.2.2 Biochemicalmimicking 110
3.1.2.3 Mechanicalmimicking 110
3.1.2.4 ECMmimickingthroughorgan/tissue
decellularization 113
3.1.3 NeedforCompatibleCell-Types 114
3.2 Modelsfor3DCellCulture 115
3.2.1 Spheroids 115
3.2.2 Hydrogels 116
3.2.3 ScaffoldsandMatrices 118
3.3 Materialsfor3DCellCulture 119
3.3.1 Natural 120
3.3.2 Synthetic 121
3.3.3 Hybrid 122
3.3.3.1 Physicalblends 123
3.3.3.2 Chemicalblends 125
3.4 MethodsofCreatingScaffold/Matricesfor
3DCulture 125
3.4.1 ConventionalTechniques 126
3.4.1.1 Solventcasting/meltmolding 126
3.4.1.2 Extrusion 126
3.4.1.3 Moldingwithparticleleaching 127
3.4.1.4 Gelcastingandfreezedrying 127
3.4.1.5 Thermallyinducedphase
transition/gasfoaming 128
3.4.1.6 Fiberbonding 128
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Contents vii
3.4.1.7 Microspheresintering 128
3.4.1.8 Micro-contactprinting 128
3.4.2 AdvancedTechniques 128
3.4.2.1 Electrospinning 129
3.4.2.2 Rapidprototypingorsolidfreeform
fabrication 130
3.4.2.3 Emulsiontemplating 132
3.4.2.4 Micromolding 133
3.4.2.5 Photoplating/photolithography 133
3.4.2.6 Designedself-assembly 134
3.5 Applicationsof3DScaffolds/Matrices 138
3.5.1 InResearchandDevelopment 138
3.5.2 Diagnostics 139
3.5.3 Cell-BasedSensors 140
3.5.4 HighThroughputScreening 141
3.5.5 BiotechIndustry 141
3.5.6 DrugDelivery 142
3.5.7 BiochemicalReplacement 142
3.5.8 InTissueEngineering(TE) 142
3.5.8.1 Exvivoorganmodel 143
3.5.8.2 Tissueexplants 144
3.5.8.3 Invivotissueregeneration 144
3.5.9 Human-OrganoidModelsforPhysiology 145
4 Scaffolds/Matricesfor3DCell/TissueCulture 159
4.1 Introduction 159
4.2 Non-specificinvitro3DCulture 165
4.3 TissueEngineering 165
4.4 RegenerativeMedicine 167
4.4.1 Insitu 167
4.4.2 Exsitu 167
4.5 AvailableTechnologies 168
4.5.1 Matrigel 170
4.5.2 Alvetex(cid:2)R 171
4.5.3 3D-Biotek(cid:2)R 172
4.5.4 AlgiMatrix(cid:2)R 3DCellCultureSystem 172
4.5.5 PuraMatrix(cid:2)R 173
4.5.6 Integra(cid:2)R 174
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viii Contents
4.5.7 PriMatrix 176
4.5.8 Hyalubrix(cid:2)R/Hyalgan 176
4.5.9 ExtracelTM 177
4.5.10 Mebiol 178
4.5.11 UpCellTM 179
4.5.12 BioVaSc-TERM(cid:2)R 180
4.5.13 Corgel(cid:2)R 180
4.5.14 Opsite,BiobraneandOasis(cid:2)R WoundMatrix 181
4.5.15 Cyto-Matrix 182
4.5.16 AmnioGraft(cid:2)R 182
4.5.17 Artiss/Tisseel 183
4.5.18 ECMAnalog(cid:2)R 185
4.6 FutureTrends/ChallengesAhead 187
RecommendedReading 197
Glossary 199
Index 203
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Preface
Cell culture is an in vitro laboratory technique widely used for
growingplantandanimalcells.Itisprimarilyutilizedtolearnand
evaluatecellularprocessesunderartificialbutdefinedexperimental
conditions.Isolatedcellsandcelllinesareenabledtogrowexvivoin
glassorplasticappliancesusingartificialnutrientsandsupplements
for targeted explorations. The composition of liquid medium is
adjusted to meet the requirement of different types of cells to be
cultured. Till now culturing cells in a flat-bottomed flask or Petri
dish where cells are allowed to expand on a flat surface, i.e., in
twodimensionshasbeenacommonpractice.Thetechniqueforits
ease is now widely adopted in clinics for diagnostic purposes. Use
of cell culture techniques has not remained limited to unraveling
the mysteries of cell biology but also extended to other areas like
qualitativeandquantitativeassessmentofmetabolicactivities.
Thepossibilityofgrowinghealthyandviablecellsexvivoledto
thehumanurgetowardsanewdirectionforachievinglongevityby
replacingtheailingordiseasedbodytissueswithrenewed-healthy
cellsandtissues.Organtransplantationhasbeenviewedasthemost
preferredchoiceinthestateofkidneyandheartfailures.Tumorous
tissuesalsoleavenochoicebuttoberemovedandifpossiblereplace
theorganwiththenormalhealthierones.Replacementwithhealthy
normaltissuescouldbeabetterchoiceforcanceroustissuebefore
metastasis. Even after the onset of metastasis a swapping with
healthy tissue might provide a control as the source of malignant
signalingwouldnotbethere.Though,identifyinganaccuratematch
andawillingdonorhasalwaysbeenscarce.Thisledtoanexpedition
for generating ex vivo implants by growing patients’ own cells.
Such artificially created functional tissue is expected to replace
the diseased tissue/organ without any fear of rejection. The quest
