Neural Engineering (eBook)

Lijie Grace Zhang is Associate Professor in the School of Engineering and Applied Science at The George Washington University, and is Director of the Bioengineering Laboratory for Nanomedicine and Tissue Engineering. She is also Associate Editor-in-Chief of International Journal of Nanomedicine. David Kaplan holds an Endowed Chair, the Stern Family Professor of Engineering, at Tufts University. He is Professor and Chair of the Department of Biomedical Engineering and also holds faculty appointments in the School of Medicine, the School of Dental Medicine, Department of Chemistry, and the Department of Chemical and Biological Engineering. He serves on the editorial boards of numerous journals and is Associate Editor for the ACS journal Biomacromolecules.

Preface 6
Contents 8
Chapter 1: Biomaterials and 3D Printing Techniques for Neural Tissue Regeneration 10
1.1 Introduction 10
1.2 Neural Tissue Engineering 12
1.2.1 Criteria for Ideal Tissue-Engineered Neural Scaffolds 12
1.2.2 Biomaterials for Nerve Scaffold 12
1.2.2.1 Natural Biomaterials 12
1.2.2.2 Synthetic Biomaterials 14
1.2.2.3 Electrically Conductive Biomaterials 15
1.2.2.4 Carbon-Based Nanomaterials 16
1.3 3D Printing Techniques for Nerve Regeneration 18
1.3.1 Inkjet Bioprinting 18
1.3.2 Stereolithography 20
1.3.3 Extrusion-Based Printing 24
1.3.4 Bioplotting 25
1.3.5 Emerging Novel 3D Printing Technologies 26
1.4 Conclusion and Future Directions 28
References 28
Chapter 2: Stem Cells, Bioengineering, and 3-D Scaffolds for Nervous System Repair and Regeneration 34
2.1 Introduction 36
2.2 Stem Cells 36
2.2.1 Pluripotent Stem Cells 37
2.2.1.1 Pluripotent Embryonic Stem Cells 37
2.2.1.2 Induced Pluripotent Stem Cells 39
2.2.2 Multipotent Stem Cells for Neural Repair Strategies 42
2.2.2.1 Neural Stem Cells 43
2.2.2.2 Non-neural Adult Stem Cells 44
2.2.2.3 Cellular Reprogramming Strategies 49
Direct Conversion Using Transcription Factors or Small Molecules 49
Ex Vivo Gene Therapy Approaches for Neuroprotection 50
2.3 3-D Scaffolds for Neural Tissue Engineering 53
2.3.1 Nano/Microparticle Systems 63
2.3.2 Nano/Microfiber Scaffolds 68
2.3.3 Other Types of Scaffolds 70
2.4 Stem Cell-Based Approaches Coupled with Bioengineering for Translational Applications 73
2.5 Conclusions and Future Directions 74
References 75
Chapter 3: Engineering Neuronal Patterning and Defined Axonal Elongation In Vitro 91
3.1 Introduction 91
3.2 A Survey of Approaches 93
3.3 Physical Topography 94
3.4 Printing Processes 94
3.4.1 Microcontact Printing 94
3.4.2 Inkjet Printing 96
3.4.3 Matrix-Assisted Pulsed Laser Evaporation-Direct Write Printing 98
3.5 Photolithography 100
3.5.1 Photopatterning Two-Dimensional Substrates 100
3.5.2 Three-Dimensional Photoimmobilization of Guidance Cues 102
3.5.3 Stereolithography of Hydrogel Guidance Structures 103
3.5.4 Laser-Assisted Protein Adsorption by Photobleaching 104
3.5.5 Digital Projection Photolithography 105
3.6 Microfluidic Applications 107
3.6.1 Material Deposition 107
3.6.2 Gradient Formation 108
3.6.3 Fluid Flow 109
3.6.4 Block Cell Printing 109
3.7 Subtractive Fabrication 110
3.7.1 Photoablation 110
3.7.2 Photothermal Etching 111
3.7.3 Nanoshaving 113
3.8 Optical Guidance 113
3.8.1 Laser Micromanipulation 113
3.8.2 Optical Tweezers 114
3.8.3 Ultrafast Laser Microbeams 115
3.8.4 Neuronal Beacon 115
3.9 Magnetic Applications 116
3.9.1 Magnetic Fields 116
3.9.2 Magnetic Fiber Alignment 116
3.9.3 Magnetic Nanoparticles 117
3.10 Electric Fields 117
3.11 Comparison of Methods 118
References 119
Chapter 4: Building Blocks for Bottom-Up Neural Tissue Engineering: Tools for In Vitro Assembly and Interrogation of Neural Circuits 130
4.1 Introduction 130
4.2 Molecular Tools for Probing Neuronal Function 131
4.2.1 Genetically Encoded Tools: Detecting and Controlling Neural Activity in Defined Cell Types 131
4.2.1.1 Genetically Encoded Indicators of Neuronal Activity and Signaling 132
4.2.1.2 Genetically Encoded Tools for Controlling Neural Circuit Function 134
4.2.1.3 Simultaneous Control and Imaging Using Genetically Encoded Tools 134
4.3 Biofabrication Methods 136
4.3.1 Bioprinting 136
4.3.1.1 Inkjet Bioprinting 137
4.3.1.2 Microextrusion Bioprinting 138
4.3.1.3 Laser-Assisted Bioprinting 138
4.3.2 Microassembly Approaches 139
4.3.2.1 Self-Assembly 140
4.3.2.2 Guided Assembly 140
Magnetic Field-Guided Assembly 141
Acoustic Field-Guided Assembly 143
Geometric Recognition-Guided Assembly 143
Liquid-Based Template Assembly 143
4.3.2.3 Direct Assembly 144
Digital Patterning 144
Microrobotics 144
Conclusions 145
References 146
Chapter 5: Electrically Conductive Materials for Nerve Regeneration 152
5.1 Introduction 152
5.2 Conductive Materials 154
5.2.1 Evaluating Electrical Properties 154
5.2.2 Inherently Conductive Polymers 156
5.2.2.1 Synthesis 156
5.2.2.2 Polypyrrole 158
5.2.2.3 PANi 164
5.2.2.4 Polythiophenes 165
5.2.3 Piezoelectric Materials 165
5.3 Nanostructured Carbons 169
5.4 In Vivo Studies 173
5.5 Conclusions and Future Directions 175
5.5.1 Electrical Stimulation: Incomplete Mechanistic Evidence 175
5.5.2 Future Work 178
5.6 Conclusion 178
References 179
Chapter 6: Bioactive Nanomaterials for Neural Engineering 187
6.1 Introduction 187
6.1.1 Nerve Regeneration and the Roles of Extracellular Matrix Elements 187
6.1.1.1 Peripheral Nervous System 188
6.1.1.2 Central Nervous System 189
6.1.2 Blood–Brain Barrier and Blood–Spinal Cord Barrier 190
6.1.3 Challenges in Engineering Biomaterials for Nervous System Repair 191
6.2 Biomaterial Design for Peripheral Nerve Repair 192
6.2.1 Engineering Topographical and Mechanical Properties for Neural Guidance 193
6.2.2 Surface Chemistry and Biochemical Modifications to Increase Nerve Regeneration 194
6.2.3 Enhancing Regeneration by Electrical Stimulation via Conductive Biomaterials 196
6.3 Biomaterial Design for Central Nervous System Repair 197
6.3.1 Mimicking Extracellular Matrix of Central Nervous System 198
6.3.1.1 Chemical Signals 198
6.3.1.2 Mechanical and Physical Cues 199
6.3.2 Approaches for Drug Delivery to Central Nervous System 200
6.3.2.1 Material Properties and Methods for Drug Delivery 200
6.3.2.2 Drug Selection 202
6.4 Concluding Remarks 203
References 203
Chapter 7: Cell Sources and Nanotechnology for Neural Tissue Engineering 213
7.1 Introduction 213
7.2 Cell Sources for Neural Tissue Engineering 215
7.2.1 Stem Cells 215
7.2.1.1 Embryonic Stem Cells 215
7.2.1.2 Fetal and Neonatal Stem Cells 217
7.2.1.3 Adult Stem Cells 217
7.2.1.4 Induced Pluripotent Stem Cell 218
7.2.2 Glial Cells 218
7.3 Nanotechnology for Neural Tissue Engineering 220
7.3.1 Carbon-Based Nanomaterials 220
7.3.1.1 Carbon Nanotubes 220
7.3.1.2 Carbon Nanofibers 222
7.3.1.3 Graphene 223
7.3.2 Engineered Nanostructured Neural Scaffolds 224
7.3.2.1 Electrospinning Nanofibrous Scaffolds 224
7.3.2.2 Self-Assembling Nanofiber Scaffolds 226
7.4 Conclusions and Prospects 227
References 229
Chapter 8: Brain-Machine Interfaces: Restoring and Establishing Communication Channels 233
8.1 A Neuroprosthetic Arm 234
8.1.1 Rats Can Control Robotic Arms Using Only Their Minds 234
8.1.2 Monkeys Are Able to Use Neural Interfaces to Manipulate Computer Cursors 235
8.1.3 Monkeys Feed Themselves Using Neuroprosthetic Arms 238
8.1.4 The Disabled Are Finally Getting a Hand as Motor Neuroprostheses Enter Clinical Trials 239
8.1.5 Researchers Give the Disabled More than a Hand, for Example, an F-35 Fighter Jet 241
8.1.6 Brain-Controlled Stimulation of Muscles Presents an Alternative Pathway to Regaining Mobility 241
8.2 A Somatosensory Neuroprosthesis 242
8.2.1 Adding Feedback to Neuroprosthetic Arms Is a Touching Story 242
8.2.2 Electrical Stimulation of the Primary Somatosensory Cortex Provides a Substitute for Natural Tactile Stimuli 243
8.2.3 Closing the Sensorimotor Loop Allows for more Naturalistic Control of Neuroprostheses 245
8.3 An Auditory Neuroprosthesis 247
8.3.1 The Cochlear Implant Emerges as the First Commercially Successful Neuroprosthesis 247
8.3.2 Competition Within the Commercial Market Improves the Cochlear Implant 248
8.3.3 Interfaces in the Cochlear Nucleus or Inferior Colliculus Deliver Audio Signals Directly to the Brain 250
8.4 A Visual Neuroprosthesis 251
8.4.1 Interfaces in the Visual Cortex Deliver Visual Signals Directly to the Brain 252
8.4.2 Interfacing with the Retina May Allow for Less Complex Encoding of the Visual Signal 254
8.5 A Brain-to-Brain Interface 256
8.5.1 Telepathically Linked Rats Are Able to Cooperatively Complete Tasks While in Separate Locations 256
8.5.2 An Interspecies Brain-To-Brain Interface Allows a Human to Twitch a Rat’s Tail 257
8.5.3 A Brain-to-Brain Interface in Humans Can Be Used to Cooperatively Play Video Games or Send Morse Code 257
8.6 Closing Words 259
References 260
Chapter 9: In Vitro Modeling of Nervous System: Engineering of the Reflex Arc 266
9.1 Introduction 267
9.1.1 Importance of In Vitro Engineering of Neural System 267
9.1.2 Major Neural Systems that Have Been Engineered In Vitro 268
9.2 Establishment of In Vitro Biologically Based Neural Models 268
9.2.1 Cell Sources for Neural Engineering 268
9.2.2 In Vitro Engineering of the Reflex Arc 271
9.2.2.1 Overview of the Reflex Arc 271
9.2.2.2 In Vitro Models of the Neuromuscular Junction 272
9.2.2.3 In Vitro Modeling of Other Components of the Reflex Arc 274
9.3 Interdisciplinary Technologies Utilized for Engineering of the Reflex Arc 276
9.3.1 Surface Modification for Directing Neural Circuit Formation 276
9.3.1.1 Topographical Patterning/Microfluidic Devices 276
9.3.1.2 Direct Chemical Modification of Surfaces 277
9.3.1.3 Adsorptive Modification of Surfaces 278
9.3.2 MEA System for Controlling/Monitoring Neuronal Activation 279
9.3.3 Cantilever Systems and Their Application in Monitoring Muscle Contraction 281
9.4 Addition of Systematic Complexity to Nervous System Models to Mimic In Vivo Conditions 284
9.4.1 Blood–Brain Barrier 284
9.4.1.1 The Relationship Between the PNS, CNS, and the BBB 284
9.4.1.2 Concept of the Neurovascular Unit 285
9.4.1.3 Current Development and Future Directions of In Vitro NVU Models 285
9.4.2 Organ-on-a-Chip Systems Under Microfluidic Circulation to Mimic In Vivo Conditions 286
9.4.3 Inclusion of Other Tissues to Reproduce Systemic Interactions 288
9.5 Summary and Perspectives 288
References 289
Index 304