Handbook of Neural Engineering

Dr. Stephanie Willerth, Ph.D., F.C.S.S.E., F.B.S.E., is a Full Professor in Biomedical Engineering at the University of Victoria, where she has dual appointments in the Department of Mechanical Engineering and the Division of Medical Sciences. She runs an internationally recognized research group focused on tissue engineering and regenerative medicine. She also holds an appointment with the School of Biomedical Engineering at the University of British Columbia. She was elected to the Royal Society of Canada’s College of New Scholars in 2021 and received the 2021 Engineers and Geoscientists of British Columbia’s Teaching Award for Excellence. She founded the award winning start-up company Axolotl Biosciences, which sells high-quality bioinks for bioprinting human tissue models. Dr. Willerth is an active member of the steering committee of the B.C. Regenerative Medicine Initiative and the Stem Cell Network. She also serves as a staff scientist at Creative Destruction Lab. Dr. Willerth served as the Director of the Centre for Biomedical Research and the Biomedical Engineering undergraduate program at the University of Victoria from 2018-2021 and as the President of Canadian Biomaterials Society from 2018-2019. Dr. Willerth is the author of Engineering Neural Tissue from Stem Cells, published by Elsevier Academic Press in 2016.

Contributors xiii
Preface xix
Acknowledgments xxi
1. Introduction to neural engineering 1
Stephanie Willerth
1 Introduction 1
2 Biomedical engineering and the evolution of neural engineering 5
3 Biological considerations for neural engineering 7
4 Neural engineering strategies 10
5 Emerging technologies for neural engineering 11
6 Conclusions 13
References 13
SECTION 1 Biological considerations for neural engineering
2. Overview of the structure and function of the nervous system 17
1 Introduction 17
2 Early development of the nervous system 18
3 Functional anatomy of the CNS 21
4 Cell types 26
5 Neuronal communication 32
6 Summary and conclusions 41
References 41
3. Cellular biology of the central nervous system 49
1 Introduction 49
2 Neurons 49
3 Astrocytes 60
4 Microglia 66
5 Oligodendrocytes 72
6 Summary and conclusions 78
References 78
4. Extracellular matrix of the nervous system 97
1 Introduction 99
2 Composition and assembly of ECM in the nervous system 100
3 ECM during brain development 108
4 Neural ECM in aging and disease 115
5 Engineering ECM for human brain tissue models 120
6 Summary 130
References 131
5. The immune system and its role in the nervous system 149
1 Introduction 149
2 Overview of the immune system 150
3 Immunology within the nervous system 153
4 Interactions between the nervous system and the systemic
immune system 158
5 Neuroimmunity in injury, disease, and aging 159
6 Methods in neuroimmunology 162
7 Neuroimmune engineering 165
8 Conclusion 171
References 171
6. Modulating disease states of the central nervous system:
Outcomes of neuromodulation on microglia 179
1 Introduction 179
2 CNS seen from the microglial angle 183
3 Memory disorders 187
4 Disorders of inhibition 194
5 Disorders of consciousness and coma 203
6 Challenges and limitations of the techniques 212
7 Conclusion 213
References 214
7. The effect of traumatic injuries on the nervous system 231
1 Traumatic brain injury: Context and definitions 231
2 Primary injury and the onset of traumatic brain injury pathophysiology 234
3 The continuum of secondary injury 237
4 Acute phase 237
5 Subacute phase 248
6 Chronic phase 250
7 Repetitive TBI 253
8 Future directions in neurotrauma research 255
References 258
8. Chronic pain as a neurological disease and neural engineering strategies for its management 271
1 Pain is a protective mechanism necessary for survival 271
2 The nociceptive pain circuit 271
3 Chronic pain is a disease in its own right 284
4 Neuromodulation as an engineering approach in managing chronic pain 289
5 Conclusions 293
Acknowledgment 293
References 293
SECTION 2 Neural engineering strategies
9. An overview of noninvasive imaging strategies in neural engineering 301
1 Introduction 301
2 Utility of imaging modalities to neural engineering 303
3 Optical imaging 304
4 Ultrasound (US) 313
5 Magnetic resonance imaging (MRI) 315
6 X-rays and computed tomography (CT) 326
7 Positron emission tomography (PET) and single photon emission computed tomography (SPECT) 329
8 Electroencephalogram/magnetoencephalography (EEG/MEG) 333
9 Conclusions 335
References 335
10. Brain-computer interface 351
1 Defining brain-computer interface 351
2 History of BCI 354
3 Innovations in modern-day BCIS 357
4 Brief introduction to the nervous system 359
5 BCI types 360
6 BCI components 365
7 BCI applications 374
8 Challenges and future direction 378
References 380
11. Neuroprosthetics 389
1 Auditory prosthesis 389
2 Deep brain stimulation 394
3 Spinal cord neuroprosthetics 396
4 Neuromuscular prosthetics 398
5 Neuroprosthetics for internal organs 400
6 Outlook: The next generation of neuroprosthetics 404
References 406
12. Neural tissue engineering 413
1 Functional bio/nanomaterials 415
2 In vitro 3D tissue culture platforms for nervous system (spheroids and organoids) 430
3 Microfluidic systems 439
4 Scaffolding (implantable neural interfaces) 444
5 Electrical stimulations 452
6 Summary 457
References 459
SECTION 3 Emerging technologies for neural engineering
13. Optogenetics for neural tissue engineering applications 479
1 Biophysics of microbial rhodopsin 479
2 Diversity of optogenetic channels, pumps, and receptors 483
3 Use of light-sensitive proteins to manipulate intracellular signaling and metabolism 485
4 Visualization of cell activity 488
5 Optogenetics in biological systems 491
6 Optogenetics in medical applications 493
7 Future aims in optogenetic engineering 498
References 499
14. Neuroengineering: History, modeling, and deliverables 505
1 History of genomic editing 505
2 Neuronal cell models 510
3 In vivo models and applications of delivery 523
References 534
15. Recent developments in 3D bioprinting for neural tissue engineering 549
1 Overview of modeling neural tissue: From 2D and
3D culture systems to 3D bioprinting 549
2 How 3D bioprinting works 557
3 Design of biomaterial-based bioinks to mimic the neural microenvironment 561
4 3D bioprinted models for studying neurodegenerative diseases 576
5 Conclusion 579
References 579
16. Maximizing the utility of brain organoid models and overcoming their perceived limitations 593
1 Introduction 593
2 Current methods for generating brain organoids 595
3 Uses of brain organoids 613
4 Ethical considerations and limitations to data interpretation 616
5 Perspective and summary 616
References 617
17. Modeling the synapse and neuromuscular junction using organ-on-a-chip technology 625
1 Introduction 625
2 Synapse- and NMJ-on-a-chip: Design and fabrication 630
3 Applications of synapse and NMJ chips 633
4 Challenges and future directions 637
Acknowledgments 639
References 639
Index 645