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 xiiiPreface xixAcknowledgments xxi1. Introduction to neural engineering 1Stephanie Willerth1 Introduction 12 Biomedical engineering and the evolution of neural engineering 53 Biological considerations for neural engineering 74 Neural engineering strategies 105 Emerging technologies for neural engineering 116 Conclusions 13References 13SECTION 1 Biological considerations for neural engineering2. Overview of the structure and function of the nervous system 171 Introduction 172 Early development of the nervous system 183 Functional anatomy of the CNS 214 Cell types 265 Neuronal communication 326 Summary and conclusions 41References 413. Cellular biology of the central nervous system 491 Introduction 492 Neurons 493 Astrocytes 604 Microglia 665 Oligodendrocytes 726 Summary and conclusions 78References 784. Extracellular matrix of the nervous system 971 Introduction 992 Composition and assembly of ECM in the nervous system 1003 ECM during brain development 1084 Neural ECM in aging and disease 1155 Engineering ECM for human brain tissue models 1206 Summary 130References 1315. The immune system and its role in the nervous system 1491 Introduction 1492 Overview of the immune system 1503 Immunology within the nervous system 1534 Interactions between the nervous system and the systemicimmune system 1585 Neuroimmunity in injury, disease, and aging 1596 Methods in neuroimmunology 1627 Neuroimmune engineering 1658 Conclusion 171References 1716. Modulating disease states of the central nervous system:Outcomes of neuromodulation on microglia 1791 Introduction 1792 CNS seen from the microglial angle 1833 Memory disorders 1874 Disorders of inhibition 1945 Disorders of consciousness and coma 2036 Challenges and limitations of the techniques 2127 Conclusion 213References 2147. The effect of traumatic injuries on the nervous system 2311 Traumatic brain injury: Context and definitions 2312 Primary injury and the onset of traumatic brain injury pathophysiology 2343 The continuum of secondary injury 2374 Acute phase 2375 Subacute phase 2486 Chronic phase 2507 Repetitive TBI 2538 Future directions in neurotrauma research 255References 2588. Chronic pain as a neurological disease and neural engineering strategies for its management 2711 Pain is a protective mechanism necessary for survival 2712 The nociceptive pain circuit 2713 Chronic pain is a disease in its own right 2844 Neuromodulation as an engineering approach in managing chronic pain 2895 Conclusions 293Acknowledgment 293References 293SECTION 2 Neural engineering strategies9. An overview of noninvasive imaging strategies in neural engineering 3011 Introduction 3012 Utility of imaging modalities to neural engineering 3033 Optical imaging 3044 Ultrasound (US) 3135 Magnetic resonance imaging (MRI) 3156 X-rays and computed tomography (CT) 3267 Positron emission tomography (PET) and single photon emission computed tomography (SPECT) 3298 Electroencephalogram/magnetoencephalography (EEG/MEG) 3339 Conclusions 335References 33510. Brain-computer interface 3511 Defining brain-computer interface 3512 History of BCI 3543 Innovations in modern-day BCIS 3574 Brief introduction to the nervous system 3595 BCI types 3606 BCI components 3657 BCI applications 3748 Challenges and future direction 378References 38011. Neuroprosthetics 3891 Auditory prosthesis 3892 Deep brain stimulation 3943 Spinal cord neuroprosthetics 3964 Neuromuscular prosthetics 3985 Neuroprosthetics for internal organs 4006 Outlook: The next generation of neuroprosthetics 404References 40612. Neural tissue engineering 4131 Functional bio/nanomaterials 4152 In vitro 3D tissue culture platforms for nervous system (spheroids and organoids) 4303 Microfluidic systems 4394 Scaffolding (implantable neural interfaces) 4445 Electrical stimulations 4526 Summary 457References 459SECTION 3 Emerging technologies for neural engineering13. Optogenetics for neural tissue engineering applications 4791 Biophysics of microbial rhodopsin 4792 Diversity of optogenetic channels, pumps, and receptors 4833 Use of light-sensitive proteins to manipulate intracellular signaling and metabolism 4854 Visualization of cell activity 4885 Optogenetics in biological systems 4916 Optogenetics in medical applications 4937 Future aims in optogenetic engineering 498References 49914. Neuroengineering: History, modeling, and deliverables 5051 History of genomic editing 5052 Neuronal cell models 5103 In vivo models and applications of delivery 523References 53415. Recent developments in 3D bioprinting for neural tissue engineering 5491 Overview of modeling neural tissue: From 2D and3D culture systems to 3D bioprinting 5492 How 3D bioprinting works 5573 Design of biomaterial-based bioinks to mimic the neural microenvironment 5614 3D bioprinted models for studying neurodegenerative diseases 5765 Conclusion 579References 57916. Maximizing the utility of brain organoid models and overcoming their perceived limitations 5931 Introduction 5932 Current methods for generating brain organoids 5953 Uses of brain organoids 6134 Ethical considerations and limitations to data interpretation 6165 Perspective and summary 616References 61717. Modeling the synapse and neuromuscular junction using organ-on-a-chip technology 6251 Introduction 6252 Synapse- and NMJ-on-a-chip: Design and fabrication 6303 Applications of synapse and NMJ chips 6334 Challenges and future directions 637Acknowledgments 639References 639Index 645