Begell House Inc.
Critical Reviews™ in Biomedical Engineering
CRB
0278-940X
39
3
2011
Transformative Research in Neural Engineering: Foreword / Editors' Commentary (Volume 3)
181-183
10.1615/CritRevBiomedEng.v39.i3.10
Bryan J.
Pfister
Department of Biomedical Engineering, New Jersey Institute of Technology, USA
D. Kacy
Cullen
University of Pennsylvania, Philadelphia, PA 19104, USA
Neural engineering is in the midst of a renaissance. The main goal of neural engineering is to develop solutions to neurological, neurosurgical, and rehabilitative problems. As neuroscientists and neural engineers, we are in an early period of discovery where we are defining the limitations both technologically and biologically of how we can fundamentally alter the function of the nervous system. This issue of Critical Reviews in Biomedical Engineering is volume three of a three volume series focused on neural engineering. The theme of this issue is "Transformative Research in Neural Engineering."
Microfluidic and Compartmentalized Platforms for Neurobiological Research
185-200
10.1615/CritRevBiomedEng.v39.i3.20
Anne
Taylor
1Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA
Noo Li
Jeon
WCU Multiscale Mechanical Design Division, School of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, Korea
compartmentalized devices
neuron cell culture
microfluidic devices
microfluidic platforms
compartmentalization
central axons
axon compartment
synaptic compartment
Methods to compartmentalize neurons allow distinct neuronal segments (i.e., cell bodies, axons, dendrites, or synapses) to be accessed, visualized, and/or manipulated. Compartmentalization has resulted in multiple studies that would not otherwise be possible in vivo or in traditional random cultures, such as investigations of axonal transport, biochemical analysis of axons, and axonal injury/regeneration. Chambers for compartmentalizing neurons were first developed for long projection peripheral neurons in the 1970s using machined Teflon dividers and relied on manually applied grease layers to spatially and fluidically separate distal axons from their cell bodies. More recently microfabrication and soft lithography techniques have been used to create compartmentalized microfluidic platforms, relying on microgrooves contained within a solid barrier through which axons and dendrites are able to extend, but not their cell bodies. These platforms are unique in their ability to culture central nervous system (CNS) neurons and allow high-resolution live imaging. These microfluidic platforms have allowed new investigations of axonal and synaptic biology in the CNS. Moreover, these microfluidic platforms offer improvements for other neural cell and tissue preparations. In this review we discuss traditional methods for compartmentalization, compartmentalized microfluidic platforms, and their use for neurobiology. Lastly, we discuss the use of these platforms for defining and manipulating synapses both pharmacologically and by electrical stimulation and recording.
Neural Tissue Engineering and Biohybridized Microsystems for Neurobiological Investigation In Vitro (Part 1)
201-240
10.1615/CritRevBiomedEng.v39.i3.30
D. Kacy
Cullen
University of Pennsylvania, Philadelphia, PA 19104, USA
John A.
Wolf
Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania,
Philadelphia, PA, USA; Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
Varadraj N.
Vernekar
Coulter Dept. of Biomedical Engineering, Georgia Institute of Technology / Emory University, Atlanta, GA, USA
Jelena
Vukasinovic
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
Michelle C.
LaPlaca
Coulter Dept. of Biomedical Engineering, Georgia Institute of Technology / Emory University, Atlanta, GA, USA
neural engineering
neuroengineering
three-dimensional
3-D culture
neural culture
axon
coculture
extracellular matrix
neuron
astrocytes
traumatic brain injury
biohybrid
microsystems
Advances in neural tissue engineering have resulted in the development and implementation of three-dimensional (3-D) neural cellular constructs, which may serve as neurofidelic in vitro investigational platforms. In addition, interfacing these 3-D cellular constructs with micro-fluidic and/or micro-electrical systems has created biohybridized platforms, providing unprecedented 3-D microenvironmental control and allowing noninvasive probing and manipulation of cultured neural cells. Cells in the brain interact within a complex, multicellular environment with tightly coupled 3-D cell-cell/cell−extracellular matrix (ECM) interactions; yet most in vitro models utilize planar systems lacking in vivo−like ECM. As such, neural cultures with cells distributed throughout a thick (>500 μ;m), bioactive extracellular matrix may provide a more physiologically relevant setting to study neurobiological phenomena than traditional planar cultures. This review presents an overview of 2-D versus 3-D culture models and the state of the art in 3-D neural cell-culture systems. We then detail our efforts to engineer a range of 3-D neural cellular constructs by systematically varying parameters such as cell composition, cell density, matrix constituents, and mass transport. The ramifications on neural cell survival, function, and network formation based on these parameters are specifically addressed. These 3-D neural cellular constructs may serve as powerful investigational platforms for the study of basic neurobiology, network neurophysiology, injury/disease mechanisms, pharmacological screening, or test-beds for cell replacement therapies. Furthermore, while survival and growth of neural cells within 3-D constructs poses many challenges, optimizing in vitro constructs prior to in vivo implementation offers a sound bioengineering design approach.
Neural Tissue Engineering for Neuroregeneration and Biohybridized Interface Microsystems In vivo (Part 2)
241-259
10.1615/CritRevBiomedEng.v39.i3.40
D. Kacy
Cullen
University of Pennsylvania, Philadelphia, PA 19104, USA
John A.
Wolf
Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania,
Philadelphia, PA, USA; Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
Douglas H.
Smith
Department of Neurosurgery, Center for Brain Injury & Repair, University of Pennsylvania, Philadelphia, PA
Bryan J.
Pfister
Department of Biomedical Engineering, New Jersey Institute of Technology, USA
neural engineering
neuroengineering
3-D neural culture
axon
neuron
peripheral nerve injury
spinal cord injury
transplantation
Neural tissue engineering offers tremendous promise to combat the effects of disease, aging, or injury in the nervous system. Here we review neural tissue engineering with respect to the design of living tissue to directly replace damaged or diseased neural tissue, or to augment the capacity for nervous system regeneration and restore lost function. This article specifically addresses the development and implementation of tissue engineered three-dimensional (3-D) neural constructs and biohybridized neural-electrical microsystems. Living 3-D neural constructs may be "pre-engineered" in vitro with controlled neuroanatomical and functional characteristics for neuroregeneration, to recapitulate lost neuroanatomy, or to serve as a nervous tissue interface to a device. One application being investigated is developing constructs of axonal tracts that, upon transplantation, may facilitate nervous system repair by directly restoring lost connections or by serving as a targeted scaffold to promote host regeneration by exploiting axon-mediated axonal regeneration. In another application, living nervous tissue engineered constructs are being investigated to biohybridize neural-electrical interface microsystems for functional integration with the nervous system. With this design, in vivo neuritic ingrowth and synaptic integration may occur with the living component, potentially exploiting a more natural integration with the nonorganic interface. Overall, the use of tissue engineered 3-D neural constructs may significantly advance regeneration or device-based deficit mitigation in the nervous system that has not been achieved by non-tissue engineering approaches.