3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine

3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine, Second Edition provides an in-depth introduction to bioprinting and nanotechnology and their industrial applications. Sections cover 4D Printing Smart Multi-responsive Structure, Cells for Bioprinting, 4D Printing Biomaterials, 3D/4D printing functional biomedical devices, 3D Printing for Cardiac and Heart Regeneration, Integrating 3D printing with Ultrasound for Musculoskeletal Regeneration, 3D Printing for Liver Regeneration, 3D Printing for Cancer Studies, 4D Printing Soft Bio-robots, Clinical Translation and Future Directions. The book's team of expert contributors have pooled their expertise in order to provide a summary of the suitability, sustainability and limitations of each technique for each specific application. The increasing availability and decreasing costs of nanotechnologies and 3D printing technologies are driving their use to meet medical needs. This book provides an overview of these technologies and their integration. 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine Copyright Contents List of contributors Preface 1 Nanotechnology: A Toolkit for Cell Behavior 1.1 INTRODUCTION 1.2 NANOBIOMATERIALS FOR TISSUE REGENERATION 1.2.1 CARBON NANOBIOMATERIALS 1.2.1.1 Carbon Nanotubes 1.2.1.2 Carbon Nanofibers 1.2.1.3 Graphene 1.2.2 SELF-ASSEMBLING NANOBIOMATERIALS 1.2.2.1 Self-Assembling Nanotubes 1.2.2.2 Self-Assembling Nanofibers 1.2.3 POLYMERIC AND CERAMIC NANOBIOMATERIALS 1.2.3.1 Polymeric Nanobiomaterials 1.2.3.2 Ceramic Nanobiomaterials and Ceramic-Polymer Nanocomposites 1.3 3D NANO/MICROFABRICATION TECHNOLOGY FOR TISSUE REGENERATION 1.3.1 3D NANOFIBROUS AND NANOPOROUS SCAFFOLDS FOR TISSUE REGENERATION 1.3.1.1 Electrospun Nanofibrous Scaffolds for Tissue Regeneration 1.3.1.2 Other 3D Nanofibrous/Nanoporous Scaffolds for Tissue Regeneration 1.3.2 3D PRINTING OF NANOMATERIAL SCAFFOLDS FOR TISSUE REGENERATION 1.3.2.1 3D Printing Techniques for Tissue Regeneration 1.3.2.2 3D Printing of Nanomaterial Scaffolds for Tissue Regeneration 1.4 CONCLUSION AND FUTURE DIRECTIONS Acknowledgments Questions References 2 Bioprinting of Biomimetic Tissue Models for Disease Modeling and Drug Screening 2.1 Introduction 2.2 Current 3D Bioprinting Approaches to Build Biomimetic Tissue Models 2.2.1 Current 3D Bioprinting Technology 2.2.1.1 Inkjet-Based Bioprinting 2.2.1.2 Extrusion-Based Bioprinting 2.2.1.3 Light-Based Bioprinting 2.2.1.3.1 TPP-Based Bioprinting 2.2.1.3.2 DLP-Based Bioprinting 2.2.2 Cell Source and Preparation 2.2.3 Biomaterial Choice 2.3 Drug Screening and Disease Modeling Applications in Various Organs 2.3.1 Liver Models 2.3.2 Cardiac and Skeletal Muscle Models 2.3.2.1 Cardiac Muscle 2.3.2.2 Skeletal Muscle Models 2.3.3 Cancer Models 2.4 Challenges and Future Outlook Acknowledgments Declaration of Interests References 3 3D BIOPRINTING TECHNIQUES 3.1 Introduction 3.2 Definition and Principles of 3D Bioprinting 3.3 3D Bioprinting Technologies 3.3.1 Ink-Jet-Based Bioprinting 3.3.2 Pressure-Assisted Bioprinting 3.3.3 Laser-Assisted Bioprinting 3.3.4 Solenoid Valve-Based Printing 3.3.5 Acoustic-Jet Printing 3.4 Challenges and Future Development of 3D Bioprinting 3.5 Conclusion References 4 The Power of CAD/CAM Laser Bioprinting at the Single-Cell Level: Evolution of Printing 4.1 Introduction 4.1.1 Direct Contact Versus Direct Write for Single-Cell Printing 4.2 Basics of Laser-Assisted Printing: Overview of Systems and Critical Ancillary Materials 4.2.1 Laser-Assisted Cell Transfer System Components 4.2.2 Absorbing Film-Assisted Laser-Induced Forward Transfer 4.2.3 Matrix-Assisted Pulsed-Laser Evaporation Direct Write 4.2.4 Ancillary Materials 4.3 Matrix-Assisted Pulsed-Laser Evaporation Direct-Write Mechanistics 4.3.1 Modeling Cellular Droplet Formation 4.3.1.1 Modeling Bubble Formation-Induced Process Information 4.3.1.2 Modeling Laser-Matter Interaction Induced Thermoelastic Stress 4.3.2 Modeling of Droplet Landing Process 4.4 Postprocessing Cell Viability and Function 4.5 Case Studies and Applications Illustrating the Importance of Single-Cell Deposition 4.5.1 Isolated-Node, Single-Cell Arrays 4.5.2 Network-Level, Single-Cell Arrays 4.5.3 Next-Generation Single-Cell Arrays: Integrated, Computation-Driven Analysis 4.5.4 Example of Single-Cell Array via Matrix-Assisted Pulsed-Laser Evaporation Direct Write 4.5.5 Laser Direct Write for Neurons 4.5.5.1 Neural Development 4.5.5.2 Engineered Circuits 4.5.5.3 Nonneuronal Interactions 4.5.5.4 Outlook 4.6 Conclusion References 5 Laser Direct-Write Bioprinting: A Powerful Tool for Engineering Cellular Microenvironments 5.1 Introduction 5.1.1 Spatial Influences of the Cellular Microenvironment 5.1.2 Overview of Printing Techniques for Engineering Cellular Microenvironments 5.1.3 Laser Direct-Write Overview 5.2 Materials in Laser Direct-Write 5.2.1 Material Properties Influencing Cellular Microenvironments 5.2.2 Matrigel-Based Laser Direct-Write 5.2.3 Gelatin-Based Laser Direct-Write 5.2.4 Dynamic Release Layers 5.2.5 Additional Hydrogels Used for Printing and the Receiving Substrate 5.2.6 Nonhydrogel Receiving Substrates and Synergistic Technologies 5.3 Laser Direct-Write Applications in 2D 5.4 Laser Direct-Write Applications in 3D 5.4.1 Microenvironments in 3D 5.4.2 Layer-By-Layer Approaches 5.4.3 Laser Direct-Write Microbeads 5.4.4 Fabrication of Core-Shelled Microenvironments 5.5 Conclusions and Future Directions Acknowledgments Questions References 6 Bioink Printability Methodologies for Cell-Based Extrusion Bioprinting 6.1 Introduction 6.2 Definition of Printability 6.2.1 Consideration on Novel Bioink Development 6.2.2 Measures of Printability 6.3 Relationships Between Printing Outcomes and Rheological Properties 6.3.1 Extrudability 6.3.2 Filament Classification 6.3.3 Shape Fidelity 6.3.4 Impact of Cell Density on Printing Outcomes 6.4 Relationships Between Printing Outcomes and Process Parameters 6.4.1 Process Parameters 6.4.2 Improving Printability by Process Parameters 6.5 Models for Printability 6.6 Current Limitations 6.7 Conclusion Acknowledgments Questions References 7 Hydrogels for Bioprinting 7.1 Hydrogels in Bioprinting 7.1.1 Natural Hydrogel 7.1.1.1 Collagen 7.1.1.2 Gelatin 7.1.1.3 Fibrin 7.1.1.4 Alginate 7.1.1.5 Chitosan and Chitin 7.1.1.6 Hyaluronic Acid 7.1.1.7 Decellularized Extracellular Matrix 7.1.2 Synthetic Hydrogel 7.1.2.1 Poly(2-Hydroxyethyl Methacrylate) 7.1.2.2 Poly(vinyl alcohol) 7.1.2.3 Poly(ethylene glycol) 7.1.2.4 Poly(lactic acid) 7.1.2.5 Poloxamers 7.1.3 Bioinspired Synthetic Hydrogel 7.2 Considerations for Using Hydrogel in Bioprinting 7.2.1 General Consideration 7.2.1.1 Biocompatibility 7.2.1.2 Water Content 7.2.1.3 Swelling Behavior 7.2.1.4 Solute Transportation 7.2.1.5 Degradation 7.2.2 Technology Specific Consideration 7.2.2.1 Material Extrusion 7.2.2.1.1 Material Consideration 7.2.2.1.2 Process Consideration 7.2.2.2 Material Jetting 7.2.2.2.1 Material Consideration 7.2.2.2.2 Process Consideration 7.2.2.3 Vat Polymerization 7.2.2.3.1 Material Consideration 7.2.2.3.2 Process Consideration 7.3 Strategies Used in Hydrogel-Based Bioprinting 7.3.1 Tuning Rheology of Bioink 7.3.2 Inducing Crosslinking during Bioprinting 7.3.3 Crosslinking after Bioprinting 7.3.4 Bioprinting with Support 7.3.5 Hybrid Bioprinting 7.4 Perspective and Outlook References 8 4D Printing: 3D Printing of Responsive and Programmable Materials 8.1 INTRODUCTION 8.2 RESPONSIVE AND PROGRAMMABLE MATERIALS FOR 4D PRINTING 8.2.1 SHAPE-MEMORY POLYMERS 8.2.2 RESPONSIVE SHAPE-CHANGING POLYMERS AND THEIR COMPOSITES 8.3 REALIZATION OF 4D PRINTING 8.3.1 4D PRINTING BASED ON FUSION DEPOSITION MODELING 8.3.2 4D PRINTING BY DIRECT INK WRITING 8.3.3 4D PRINTING BY PHOTOPOLYMERIZATION 8.4 APPLICATIONS OF 4D PRINTING 8.4.1 BIOMEDICAL APPLICATIONS 8.4.1.1 Tissue Engineering 8.4.1.2 Implantable Devices 8.4.2 SOFT ROBOTS 8.4.3 FLEXIBLE ELECTRONICS 8.4.4 FOOD PROCESSING 8.5 CONCLUSION AND PROSPECTIVE QUESTIONS References 9 Blood Vessel Regeneration 9.1 Introduction 9.1.1 Additive Manufacturing 9.1.2 Important Proteins for Vasculature 9.1.3 Application to Vascular Implants 9.2 Cell-Free Scaffolds 9.2.1 Electrospinning 9.2.2 Stereolithography 9.2.3 Fused-Deposition Modeling 9.3 Cell-Based Scaffolds 9.3.1 Inkjet Printing 9.3.2 Extrusion-Based Bioprinting 9.3.2.1 Coaxial Printing 9.3.3 Laser-Assisted Printing 9.4 Comparison of the Technologies 9.4.1 Applications to the Vascular System and Other Tissue-Engineered Implants 9.5 Future Directions Acknowledgments References 10 3D PRINTING AND PATTERNING VASCULATURE IN ENGINEERED TISSUES 10.1 Introduction 10.1.1 Macroporous Constructs as Tissue Templates 10.1.2 Fabricating Fluidic Networks within Biomaterials 10.1.3 Approaches to Fabricate Endothelialized and Cell-Laden Tissue Constructs 10.1.4 Approaches to Integrate Patterned Vasculature In Vivo 10.1.5 Patterning Multiscale Vasculature with Endothelial Function 10.1.6 Angiogenesis, Vasculogenesis, and In Vivo Integration 10.1.7 Advanced Technologies which May Assist in Vascular Tissue Fabrication References 11 Craniofacial and Dental Tissue 11.1 Introduction 11.2 Clinical Need for Craniofacial and Dental Regenerative Medicine 11.2.1 Major Diagnoses and Causes 11.2.1.1 Dental Disease 11.2.1.2 Trauma 11.2.1.3 Aging 11.2.1.4 Cancer 11.2.1.5 Congenital 11.2.2 Standard-of-Care Procedures 11.2.2.1 Teeth 11.2.2.2 Bone and Cartilage 11.2.2.3 Soft Tissue 11.3 Craniofacial and Dental Regenerative Medicine Research 11.3.1 Novel Materials 11.3.2 Teeth 11.3.3 Bone 11.3.4 Temporomandibular Joint 11.4 Bone Tissue Engineering Strategies 11.4.1 Scaffolds 11.4.1.1 Ceramic/bioactive Glasses 11.4.1.2 Natural/synthetic Polymers 11.4.1.3 Composites 11.4.2 Growth Factors 11.4.3 Cell-Based Therapies 11.4.4 New Craniofacial Tissues 11.4.5 Bioreactors 11.5 Conclusions Acknowledgment References 12 3D Printing for Craniofacial Bone Regeneration 12.1 Introduction 12.2 Anatomy and Mechanics of Craniofacial Bone 12.2.1 Structure of Craniofacial Bone 12.2.2 Craniofacial Bone Biomechanics 12.3 Materials for Craniofacial Scaffold 12.3.1 Bioceramics and Bioactive Glasses 12.3.2 Metals 12.3.3 Natural and Synthetic Polymers 12.3.4 Hydrogels 12.3.5 Demineralized and Decellularized Bone Matrix 12.4 3D-Printing Techniques for Craniofacial Scaffold 12.4.1 Photopolymerization 12.4.2 Extrusion-Based Printing 12.4.3 Laser-Assisted 3D Printing 12.4.4 Binder Jetting 12.5 Enhancing the Regenerative Capability of Biomaterials in Craniofacial Bone Regeneration 12.5.1 Effect of Scaffold Geometry 12.5.2 Effect of Mesenchymal Stem Cells, Progenitor Cells Delivery 12.5.3 Effect of Dopants or Coating 12.5.4 Effect of Oxygen and Growth Factors Delivery 12.5.5 Effect of Drug Delivery 12.5.6 Effect of Gene Delivery 12.6 Case Studies: Application of Porous Scaffold Design for Clinical Applications 12.6.1 Case Study 1: Cranial Defect 12.6.2 Case Study 2: Maxillary Defect 12.6.3 Case Study 3: Mandibular Defect 12.7 Conclusion References 13 Additive Manufacturing for Bone Load Bearing Applications 13.1 Need for Bone Substitutes 13.2 Compositional, Structural and Mechanical Properties of Bone 13.2.1 Compositional Properties of Bone and Requirements for Bone substitutes 13.2.2 Structural Properties of Bone and Requirements for Bone Substitutes 13.2.3 Mechanical Properties of Bone and Requirements for Bone Substitutes 13.3 Difficulties in Achieving an Ideal Bone Substitute 13.4 Metallic Bone Substitutes 13.4.1 Metallic Materials, Limitations and Opportunities 13.4.2 AM of Metals for Bone Substitutes 13.5 Bioceramic Bone Substitutes 13.5.1 Bioceramic, Bioactive Glasses and Composite Materials 13.5.2 AM of Bioceramic Materials: Several Techniques, Limitations, and Opportunities 13.5.2.1 Liquid-based AM Approaches 13.5.2.2 Solid- or Slurry-based AM Approaches 13.5.2.3 Powder-based AM Approaches 13.6 Nanocomposite Bone Substitutes 13.6.1 Nanomaterials, Limitations, and Opportunities 13.6.2 AM of Nanocomposites: Several Techniques, Limitations and Opportunities 13.7 Conclusions References 14 3D Printing of Cartilage and Subchondral Bone 14.1 BACKGROUND 14.1.1 FUNCTION AND ORGANIZATION 14.1.2 INJURY, DISEASE, AND TREATMENT 14.2 APPLICATIONS OF 3D PRINTING 14.2.1 3D-PRINTING CARTILAGE AND SUBCHONDRAL BONE 14.2.1.1 Extrusion Printing 14.2.1.2 Inkjet Printing 14.2.1.3 Scaffold-free Printing 14.2.1.4 Freeform Reversible Embedding of Suspended Hydrogels Printing 14.2.1.5 Direct In Situ Printing 14.3 MAJOR CHALLENGES AND PITFALLS 14.3.1 CELL SOURCE 14.3.2 BIOINKS AND SCAFFOLDS 14.3.3 DELIVERY 14.4 FUTURE DIRECTIONS Acknowledgments References 15 Bioprinting for Skin 15.1 Skin, Skin Substitutes, Possible Applications for Printed Skin 15.1.1 Skin—Function and Structure 15.1.1.1 Function 15.1.2 Structure 15.1.2.1 Epidermis 15.1.2.2 Basement Membrane 15.1.2.3 Dermis 15.1.2.4 Hypodermis 15.1.2.5 Cutaneous Appendages 15.2 Skin Substitutes, Applications for Printed Skin 15.2.1 Injuries of the Skin 15.2.2 Research 15.3 Skin Substitutes Generated by Bioprinting 15.3.1 Hydrogel 15.3.2 Extrusion-Based Bioprinted Skin Cells 15.3.3 Laser-Assisted Bioprinted Skin 15.3.3.1 Schematic of the Laser-Assisted Bioprinting Setup 15.3.3.2 The Printing Process Does not Affect the Cells 15.3.3.3 Laser-Assisted Printing of Skin Tissue—In Vitro Culture 15.3.3.3.1 Tissue Formation In Vitro (Submerged Culture) 15.3.3.3.2 Tissue Formation In Vitro (Air–Liquid Interface Culture) 15.3.3.4 Laser-Assisted Printing of Skin Tissue—In Vivo Culture 15.3.4 Inkjet-Based In Situ Bioprinted Skin 15.4 Discussion of the Different Bioprinting Techniques and Clinical Applicability 15.4.1 Optimization of the Skin Equivalents 15.4.2 Technical and Biomedical Challenges 15.4.3 Stem Cells as Possible Cell Sources for Bioprinting of Skin 15.5 Conclusion Acknowledgments References 16 Nanotechnology and 3D/4D Bioprinting for Neural Tissue Regeneration 16.1 Introduction 16.2 Nanotechnology for Neural Tissue Regeneration 16.2.1 Self-assembling Nanobiomaterials 16.2.2 Electrospun Polymeric Nanofibrous Neural Scaffold 16.2.3 Carbon Nanobiomaterials 16.3 3D/4D Bioprinting for Neural Tissue Regeneration 16.3.1 3D Bioprinting for Neural Tissue Regeneration 16.3.2 4D Bioprinting for Neural Tissue Regeneration 16.4 Conclusion and Future Directions Acknowledgments Questions References 17 3D Bioprinting for Liver Regeneration 17.1 Introduction 17.2 Structural and Functional Complexity of the Liver 17.3 Liver Diseases 17.4 Regeneration of the Liver 17.5 Liver Tissue Engineering and 3D Bioprinting 17.5.1 Bioinks for 3D Bioprinting of Liver Tissues 17.5.2 3D Bioprinting 17.5.2.1 Inkjet-Based Bioprinting 17.5.2.2 Extrusion-Based Bioprinting 17.5.2.3 Vat Photopolymerization-Based Bioprinting 17.5.2.4 Kenzan Bioprinting 17.6 3D-Bioprinted Liver Tissues 17.7 Challenges and Future Perspectives Acknowledgments Questions References 18 Organ Printing 18.1 Introduction 18.1.1 Organ Printing Techniques 18.1.1.1 Microextrustion-based Printing 18.1.1.2 Ink-jet-based Printing 18.1.1.3 Laser-based Printing 18.1.2 Challenges in Organ Printing 18.1.3 Micro-Organ Printing as Physiological and Disease Platforms 18.1.3.1 Microextusion-based Printed Liver Micro-organ on a Chip 18.1.3.2 Computational Model Setup for Perfused Printed Liver Micro-organ 18.1.3.3 Steady State Simulations 18.1.4 Future Perspectives References 19 3D Bioprinting, Nanotechnology, and Intellectual Property 19.1 Introduction 19.2 Why is Intellectual Property Important? 19.3 Types of Intellectual Property 19.3.1 Patents 19.3.2 Copyrights 19.3.3 Trademarks 19.3.4 Trade Secrets 19.4 Where Does Intellectual Property Law Originate? 19.5 What Aspects of 3D Bioprinting and Nanotechnology are Protectable? 19.5.1 Hardware 19.5.2 Software 19.5.3 Methods/Processes 19.5.4 Materials 19.6 Intellectual Property Protection Limitations for Engineered Tissue 19.7 Ethical Considerations of Engineered Tissue Intellectual Property 19.8 Intellectual Property Infringement 19.8.1 Trademark Infringement 19.8.2 Trade Secret Misappropriation 19.8.3 Copyright Infringement 19.8.4 Patent Infringement 19.9 Conclusion Questions Answers to Questions Index