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Book Details
Abstract
3D tissue modelling is an emerging field used for the investigation of disease mechanisms and drug development. The two key drivers of this upsurge in research lie in its potential to offer a way to reduce animal testing with respect to biotoxicity analysis, preferably on physiology recapitulated human tissues and, additionally, it provides an alternative approach to regenerative medicine.
Integrating physics, chemistry, materials science, and stem cell and biomedical engineering, this book provides a complete foundation to this exciting, and interdisciplinary field. Beginning with the basic principles of 3D tissue modelling, the reader will find expert reviews on key fabrication technologies and processes, including microfluidics, microfabrication technology such as 3D bioprinting, and programming approaches to emulating human tissue complexity. The next stage introduces the reader to a range of materials used for 3D tissue modelling, from synthetic to natural materials, as well as the emerging field of tissue derived decellularized extracellular matrix (dECM). A whole host of critical applications are covered, with several chapters dedicated to hard and soft tissues, as well as focused reviews on the respiratory and central nervous system. Finally, the development of in vitro tissue models to screen drugs and study progression and etiologies of diseases, with particular attention paid to cancer, can be found.
3D tissue modelling is an emerging field used for the investigation of disease mechanisms and drug development. The two key drivers of this upsurge in research lie in its potential to offer a way to reduce animal testing with respect to biotoxicity analysis, preferably on physiology recapitulated human tissues and, additionally, provides an alternative approach to regenerative medicine.
Integrating physics, chemistry, materials science, and stem cell and biomedical engineering, this book provides a complete foundation to this exciting, and interdisciplinary field. Beginning with the basic principles of 3D tissue modelling, the reader will find expert reviews on key fabrication technologies and processes, including microfluidics, microfabrication technology such as 3D bioprinting, and programming approaches to emulating human tissue complexity. The next stage introduces the reader to a range of materials used for 3D tissue modelling, from synthetic to natural materials, as well as the emerging field of tissue derived decellularized extracellular matrix (dECM). A whole host of critical applications are covered, with several chapters dedicated to hard and soft tissues, as well as focused reviews on the respiratory and central nervous system. Finally, the development of in vitro tissue models to screen drugs and study progression and etiologies of diseases, with particular attention paid to cancer, can be found.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Preface | v | ||
| Contents | vii | ||
| Chapter 1 Microstereolithography | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 Photopolymerization | 2 | ||
| 1.2.1 Step-growth Polymerization | 2 | ||
| 1.2.2 Free-radical Polymerization | 4 | ||
| 1.2.3 Living Free-radical Polymerization | 4 | ||
| 1.2.4 Photoinitiators | 6 | ||
| 1.3 Biomaterial Choice for Microstereolithography | 7 | ||
| 1.3.1 Natural Polymers | 7 | ||
| 1.3.2 Synthetic Polymers | 8 | ||
| 1.3.3 Composite Materials | 9 | ||
| 1.4 Scanning-based Microstereolithography | 11 | ||
| 1.4.1 Single-photon Polymerization Scanning-based Methods | 11 | ||
| 1.4.2 Two-photon Polymerization Scanning-based Methods | 12 | ||
| 1.5 Projection-based Microstereolithography | 14 | ||
| 1.5.1 Digital Light Processing | 14 | ||
| 1.5.2 Liquid-Air Interface Polymerization Setup | 15 | ||
| 1.5.3 Liquid-substrate Polymerization Setup | 17 | ||
| 1.6 Summary and Outlook | 18 | ||
| References | 18 | ||
| Chapter 2 Extrusion-based Bioprinting | 22 | ||
| 2.1 Extrusion-based Bioprinting | 22 | ||
| 2.1.1 Bioprinting | 22 | ||
| 2.1.1.1 Benefits of Bioprinting | 23 | ||
| 2.1.1.2 Types of Bioprinting | 23 | ||
| 2.1.1.3 Bioinks | 23 | ||
| 2.1.1.3.1 Hydrogels | 24 | ||
| 2.1.1.3.2 Decellularized Extracellular Matrix Bioinks | 25 | ||
| 2.1.2 EBB Systems | 25 | ||
| 2.1.2.1 Design of EBB Systems | 25 | ||
| 2.1.2.2 Functioning of EBB Systems | 26 | ||
| 2.1.2.2.1 Design of Product and Programming | 26 | ||
| 2.1.2.2.2 Robotic Movement of EBB Systems | 27 | ||
| 2.1.2.3 Mechanisms of Extrusion | 27 | ||
| 2.1.2.3.1 Mechanical Force Extrusion Systems | 27 | ||
| 2.1.2.3.2 Pneumatic Extrusion System | 28 | ||
| 2.1.2.4 Nozzle Deposition | 28 | ||
| 2.1.2.4.1 Advanced Nozzle Designs | 29 | ||
| 2.1.3 Bioinks in Extrusion-based Bioprinting | 30 | ||
| 2.1.3.1 Hydrogels | 31 | ||
| 2.1.3.1.1 Naturally-derived Hydrogels | 31 | ||
| 2.1.3.1.2 Synthetic Hydrogels | 35 | ||
| 2.1.3.2 Decellularized ECM | 35 | ||
| 2.1.3.3 Extrusion-based Hybrid Bioprinting Materials | 36 | ||
| 2.1.4 Applications of EBB | 36 | ||
| 2.1.4.1 Tissue Engineering | 36 | ||
| 2.1.4.2 Tissue Models | 37 | ||
| 2.1.4.3 Drug Fabrication | 39 | ||
| 2.1.5 Future Directions | 39 | ||
| 2.1.6 Conclusion | 40 | ||
| References | 40 | ||
| Chapter 3 Microfluidic Platforms for Biofabrication and 3D Tissue Modeling | 49 | ||
| 3.1 Introduction | 49 | ||
| 3.2 A Brief Overview of Microfluidics | 50 | ||
| 3.3 Tissue-off-chip (fab-only) Platforms for Biofabrication | 50 | ||
| 3.3.1 Microfluidic Fabrication of Point-shaped Microtissues | 53 | ||
| 3.3.2 Microfluidic Fabrication of Line-shaped Microtissues | 55 | ||
| 3.3.3 Microfluidic Fabrication of Plane-shaped Microtissues | 57 | ||
| 3.4 Tissue-on-chip (fabless/more-than-fab) Platforms for 3D Tissue Modeling | 58 | ||
| 3.4.1 On-chip Tissue Construction and Installation Techniques | 59 | ||
| 3.4.1.1 Dynamic Microarrays for Tissue Trapping | 61 | ||
| 3.4.1.2 On-chip Tissue Housing and Anchoring Techniques | 63 | ||
| 3.4.1.3 On-chip Construction of Tissue-Tissue Interfaces | 64 | ||
| 3.4.2 On-chip Tissue Sensing and Stimulation Techniques | 65 | ||
| 3.4.2.1 Mechanical Stimulation | 66 | ||
| 3.4.2.2 Chemical Sensing and Stimulation | 68 | ||
| 3.4.2.3 Electrical Sensing and Stimulation | 71 | ||
| 3.5 Conclusions | 72 | ||
| References | 72 | ||
| Chapter 4 Computational Design and Modeling of Linear and Nonlinear Elastic Tissue Engineering Scaffold Triply Periodic Minimal Surface (TPMS) Porous Architecture | 77 | ||
| 4.1 Introduction | 77 | ||
| 4.2 Methods | 80 | ||
| 4.3 Results | 83 | ||
| 4.4 Discussion | 86 | ||
| Acknowledgments | 91 | ||
| References | 91 | ||
| Chapter 5 Shear Thinning Hydrogel-based 3D Tissue Modelling | 94 | ||
| 5.1 Hydrogels: A Versatile Bioink Platform for Tissue Engineering | 94 | ||
| 5.1.1 Advantages and Challenges of Gel-phase Bioinks | 94 | ||
| 5.1.2 Current Gel-phase Bioinks | 98 | ||
| 5.2 Hydrogels as Tissue Engineering Scaffolds | 100 | ||
| 5.2.1 Oxygen and Nutrient Transport | 100 | ||
| 5.2.2 Incorporating Biochemical Signals | 101 | ||
| 5.2.3 Mechanical Properties | 102 | ||
| 5.2.4 Degradability | 103 | ||
| 5.2.5 Hierarchical Structure | 103 | ||
| 5.3 Potential Crosslinking Mechanisms for Gel-phase Inks | 104 | ||
| 5.3.1 Guest-Host | 104 | ||
| 5.3.2 Peptide-Peptide | 106 | ||
| 5.3.3 Nonspecific Hydrophobic Interactions | 106 | ||
| 5.3.4 Calcium Crosslinking | 107 | ||
| 5.3.5 Enzymatic Crosslinking | 108 | ||
| 5.3.6 Small Molecule Linkers | 109 | ||
| 5.3.7 UV Crosslinking | 109 | ||
| 5.4 Complex Architectures Using Hydrogel Inks | 110 | ||
| 5.5 Closing Remarks | 113 | ||
| References | 113 | ||
| Chapter 6 Polymers in Biofabrication and 3D Tissue Modelling | 119 | ||
| 6.1 Sources of Polymer-based Biomaterials in Biofabrication and 3D Tissue Modelling | 119 | ||
| 6.1.1 Naturally-derived Polymers | 120 | ||
| 6.1.1.1 Proteins | 120 | ||
| 6.1.1.2 Polysaccharides | 121 | ||
| 6.1.1.3 Decellularised Extracellular Matrix | 122 | ||
| 6.1.2 Synthetic Polymers | 123 | ||
| 6.2 Properties of Polymer-based Biomaterials in Biofabrication and 3D Tissue Modelling | 124 | ||
| 6.2.1 Rheology | 124 | ||
| 6.2.1.1 Viscosity | 125 | ||
| 6.2.1.2 Shear-thinning | 126 | ||
| 6.2.1.3 Yield Stress | 126 | ||
| 6.2.2 Case Study: Poloxamer 407 | 127 | ||
| 6.2.3 Solidification | 129 | ||
| 6.2.4 Final Gel Properties | 130 | ||
| 6.3 Functions of Polymer-based Biomaterials in Biofabrication and 3D Tissue Modelling | 130 | ||
| 6.3.1 Scaffolding | 130 | ||
| 6.3.1.1 Pre-fabricated Scaffolds | 130 | ||
| 6.3.1.2 Co-printing of Scaffolds for Biofabrication | 130 | ||
| 6.3.2 Cell-supporting | 131 | ||
| 6.3.2.1 In Vitro Models | 132 | ||
| 6.3.2.2 In Vivo Regeneration and Repair | 133 | ||
| 6.3.3 Facilitating Fabrication | 134 | ||
| 6.3.3.1 Supporting Structures | 134 | ||
| 6.3.3.2 Suspension Baths | 134 | ||
| 6.3.3.3 Creating Vascular Networks | 135 | ||
| 6.3.3.4 Rheology Modifier | 137 | ||
| 6.3.4 Sensing | 138 | ||
| 6.3.5 Actuating | 139 | ||
| 6.3.5.1 Shape Memory Polymers | 139 | ||
| 6.3.5.2 Anisotropic Swelling | 141 | ||
| 6.4 Summary and Outlook | 141 | ||
| Abbreviations | 141 | ||
| References | 142 | ||
| Chapter 7 Decellularized Tissue Matrix-based 3D Tissue Modeling | 148 | ||
| 7.1 Introduction | 148 | ||
| 7.2 ECM and Its Functions and Components | 150 | ||
| 7.2.1 Tissue and Organ Variety | 150 | ||
| 7.2.2 Major Elements of the ECM | 152 | ||
| 7.2.3 Functions of ECM | 153 | ||
| 7.2.3.1 Biomechanical Cues | 153 | ||
| 7.2.3.2 Biochemical Signals | 153 | ||
| 7.2.3.3 Dynamic Remodeling | 154 | ||
| 7.3 Approaches for Tissue/Organ Decellularization | 154 | ||
| 7.3.1 Physical Treatments | 154 | ||
| 7.3.2 Chemical Treatments | 155 | ||
| 7.3.2.1 Acids and Bases | 156 | ||
| 7.3.2.2 Detergents | 156 | ||
| 7.3.3 Enzymatic Treatments | 157 | ||
| 7.3.4 Sterilization | 158 | ||
| 7.3.5 Evaluation | 158 | ||
| 7.4 Applications in 3D Tissue Modeling | 159 | ||
| 7.4.1 Tissue Modeling Using Conventional Tissue Engineering Methods | 159 | ||
| 7.4.2 Tissue Modeling Using 3D Cell Printing of dECM-based Bioink | 160 | ||
| 7.5 Conclusion and Future Perspectives | 165 | ||
| Acknowledgments | 166 | ||
| References | 166 | ||
| Chapter 8 3D Tissue Modelling of the Central Nervous System | 171 | ||
| 8.1 Introduction | 171 | ||
| 8.2 Reconstruction of a 3D Neural Circuit in a Microfluidic Device | 172 | ||
| 8.2.1 Introduction | 172 | ||
| 8.2.2 Methods for In Vitro 3D Neural Circuit Platform | 173 | ||
| 8.2.2.1 Microfluidic Platform Fabrication | 173 | ||
| 8.2.2.2 Deformation of Matrigel in the Microfluidic Platform | 173 | ||
| 8.2.2.3 Primary Neural Cell Preparation and Plating in the Microfluidic Platform | 173 | ||
| 8.2.2.4 Immunostaining | 174 | ||
| 8.2.3 Results and Discussion of In Vitro 3D Neural Circuit Platform | 174 | ||
| 8.2.3.1 Deformation of Matrigel and Formation of Axon Bundle | 174 | ||
| 8.2.3.2 Formation of the Neural Circuit through the Addition of Post-synaptic Neuron Group | 175 | ||
| 8.3 Reconstruction of 3D BBB in Microfluidic Device | 177 | ||
| 8.3.1 Introduction | 177 | ||
| 8.3.2 Methods for In Vitro 3D BBB Platform | 177 | ||
| 8.3.2.1 Microfluidic Platform Fabrication | 177 | ||
| 8.3.2.2 Cell Plating for Vasculogenesis in the Microfluidic Platform | 177 | ||
| 8.3.2.3 Area of Vascular Network and Astrocytes Measurement | 178 | ||
| 8.3.2.4 Permeability Coefficient Measurement | 178 | ||
| 8.3.3 Results and Discussion of In Vitro 3D BBB Platform | 178 | ||
| 8.3.3.1 Formation of BBB by Co-culture of Neural Cell and Endothelial Cell | 178 | ||
| 8.3.3.2 Difference in Morphology and Function of BBB Depending on Media Composition Inside and Outside of Vascular Network | 179 | ||
| 8.4 Conclusion | 181 | ||
| Acknowledgments | 182 | ||
| References | 182 | ||
| Chapter 9 3D Tissue Modelling of Skeletal Muscle Tissue | 184 | ||
| 9.1 Introduction | 184 | ||
| 9.2 The Structure and Functions of Skeletal Muscle Tissue | 186 | ||
| 9.3 Skeletal Muscle Regeneration | 190 | ||
| 9.3.1 Cell Sources | 190 | ||
| 9.3.2 Satellite Cells | 190 | ||
| 9.3.3 Pericytes | 193 | ||
| 9.3.4 Fibro-adipogenic Progenitors | 193 | ||
| 9.4 Biomaterials | 194 | ||
| 9.4.1 Decellularized Matrix | 195 | ||
| 9.4.2 Natural-derived Biomaterials | 195 | ||
| 9.4.3 Synthetic Materials | 197 | ||
| 9.5 In Vitro Models for Skeletal Muscle Regeneration | 197 | ||
| 9.5.1 Electrospinning | 198 | ||
| 9.5.2 Bulk Hydrogels | 198 | ||
| 9.5.3 3D Printing | 199 | ||
| 9.6 Induction of Differentiation | 199 | ||
| 9.6.1 Mechanical Stimulation | 202 | ||
| 9.6.2 Electrical Stimulation | 205 | ||
| 9.7 In Vivo Studies | 207 | ||
| 9.8 Conclusion and Future Directions | 210 | ||
| References | 211 | ||
| Chapter 10 3D Tissue Modelling of Orthopaedic Tissues | 216 | ||
| 10.1 Introduction | 216 | ||
| 10.2 Tissue Engineering Strategies for Orthopaedic Tissues | 217 | ||
| 10.2.1 Cell-based Approach | 217 | ||
| 10.2.2 Scaffold-based Approach | 218 | ||
| 10.2.3 Additive Manufacturing (3D Printing) | 219 | ||
| 10.2.3.1 3D Bioprinting | 219 | ||
| 10.3 3D Modelling | 221 | ||
| 10.3.1 Analysis of Patient Defect | 221 | ||
| 10.3.2 Virtual Reconstruction of Defect | 222 | ||
| 10.3.3 FEM Analysis for High Efficiency and Accuracy | 222 | ||
| 10.3.4 Prototype Fabrication | 222 | ||
| 10.4 Case Reports | 223 | ||
| 10.4.1 Case Report 1 | 223 | ||
| 10.4.2 Case Report 2 | 224 | ||
| 10.4.3 Case Report 3 | 224 | ||
| 10.4.4 Case Report 4 | 224 | ||
| 10.4.5 Case Report 5 | 225 | ||
| 10.4.6 Case Report 6 | 226 | ||
| 10.5 Concept to Clinic | 226 | ||
| 10.5.1 Transforming Strategies of Bone Tissue Engineering from Lab to Patient | 226 | ||
| 10.5.2 Bridging the Breach Between the Research and Clinical Applications of Tissue Engineering | 227 | ||
| 10.6 Future Perspectives | 228 | ||
| 10.7 Conclusion | 228 | ||
| Acknowledgments | 228 | ||
| References | 229 | ||
| Chapter 11 3D Tissue Modeling of Skin Tissue | 233 | ||
| 11.1 Introduction | 233 | ||
| 11.1.1 The Need for Skin Substitutes | 234 | ||
| 11.1.2 Conventional Skin Wound Treatments | 234 | ||
| 11.2 3D Bioprinting System for Skin Tissue Engineering | 235 | ||
| 11.2.1 Bio-ink for Skin Printing | 237 | ||
| 11.2.2 Cell Source | 237 | ||
| 11.2.3 Biomaterials | 237 | ||
| 11.2.4 Basic 3D Skin Bioprinting Technique | 240 | ||
| 11.2.5 3D Skin Biofabrication | 241 | ||
| 11.3 Vascularized Skin Regeneration | 244 | ||
| 11.4 Bioprinting of Functional Artificial Skin | 246 | ||
| 11.5 Discussion | 247 | ||
| 11.6 Conclusion | 250 | ||
| References | 250 | ||
| Chapter 12 3D Modeling of Hepatic Tissue | 253 | ||
| 12.1 Introduction | 253 | ||
| 12.2 The Need for Novel Hepatic Models | 254 | ||
| 12.2.1 Predicting Drug Metabolism and Toxicity | 255 | ||
| 12.2.2 Understanding Liver Disease | 255 | ||
| 12.3 In Vivo Liver Models | 256 | ||
| 12.4 Cell Sources for In Vitro Culture | 257 | ||
| 12.5 2D Hepatocyte Cultures | 257 | ||
| 12.5.1 2D Sandwich Culture | 257 | ||
| 12.5.2 2D Co-culture Models | 258 | ||
| 12.6 3D Model Systems of the Liver | 259 | ||
| 12.6.1 Hepatic Spheroids | 259 | ||
| 12.6.2 Liver Organoids | 261 | ||
| 12.6.3 Microphysiological Hepatic Culture Systems | 263 | ||
| 12.6.4 Integrated Microphysiological Systems | 265 | ||
| 12.6.5 Bioprinted Liver Models | 266 | ||
| 12.7 Conclusion and Future Perspectives | 267 | ||
| References | 268 | ||
| Chapter 13 Microphysiological Models of the Respiratory System | 279 | ||
| 13.1 Introduction | 279 | ||
| 13.2 Early Demonstration of Lung-on-a-chip: Airway Crackle-on-a-chip | 281 | ||
| 13.3 Human Breathing Lung-on-a-chip | 283 | ||
| 13.4 Recent Advances in Lung-on-a-chip Technology | 285 | ||
| 13.4.1 A Microfabricated Organotypic Lung Model for the Study of Host-Pathogen Interactions | 285 | ||
| 13.4.2 A Microengineered Model of Human Small Airways | 287 | ||
| 13.4.3 A Specialized Disease Model of Lung Cancer | 288 | ||
| 13.4.4 A Microfluidic Model of Intravascular Thrombosis in the Alveolar System | 290 | ||
| 13.5 Future Opportunities and Challenges | 290 | ||
| References | 292 | ||
| Chapter 14 3D Tissue Model of Cancers | 294 | ||
| 14.1 Introduction | 294 | ||
| 14.2 About Cancer and the Microenvironments Shaping the Cancer | 295 | ||
| 14.2.1 Cancer-associated Fibroblasts | 297 | ||
| 14.2.2 Immune Cells | 298 | ||
| 14.2.3 Vascular Endothelial Cells | 300 | ||
| 14.2.4 Pericytes | 300 | ||
| 14.2.5 Adipocytes | 301 | ||
| 14.2.6 Extracellular Matrix | 301 | ||
| 14.3 3D Cancer Modeling Tools | 302 | ||
| 14.3.1 Shift From 2D Modeling to 3D Modeling: Why is it so Important? | 302 | ||
| 14.3.2 Microfluidic Devices | 303 | ||
| 14.3.3 Tumor Spheroids | 305 | ||
| 14.3.4 Cancer Organoids | 306 | ||
| 14.4 Conclusion | 307 | ||
| References | 308 | ||
| Chapter 15 3D Tissue Models for Toxicology | 312 | ||
| 15.1 Introduction | 312 | ||
| 15.2 3D Skin Models for Toxicology | 314 | ||
| 15.3 3D Liver Models for Toxicity | 315 | ||
| 15.4 3D Kidney Models for Toxicity | 320 | ||
| 15.5 3D Cardiac Models for Toxicity | 321 | ||
| 15.6 Conclusions and Future Outlook | 324 | ||
| Acknowledgments | 325 | ||
| References | 325 | ||
| Chapter 16 Ethics of Using Human Cells/Tissues for 3D Tissue Models | 329 | ||
| 16.1 Introduction | 329 | ||
| 16.2 Ethical Aspects of Cells | 331 | ||
| 16.2.1 Ethics Related to the Source of Cells | 331 | ||
| 16.2.1.1 Human Embryonic Stem Cells (hESCs) | 331 | ||
| 16.2.1.2 Umbilical and Adult Stem Cells | 333 | ||
| 16.3 Ethics Related to the Donation of Cells | 334 | ||
| 16.4 Ethics Related to Clinical Trials | 336 | ||
| 16.4.1 Information and Consent | 337 | ||
| 16.4.1.1 Disclosure of Information | 338 | ||
| 16.4.1.2 Comprehension of Information | 338 | ||
| 16.4.1.3 Voluntariness | 338 | ||
| 16.4.1.4 Competence | 339 | ||
| 16.4.1.5 Consent | 339 | ||
| 16.5 Conclusions | 340 | ||
| Acknowledgments | 340 | ||
| References | 341 | ||
| Subject Index | 345 |