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Critical Reviews™ in Biomedical Engineering
SJR: 0.207 SNIP: 0.376 CiteScore™: 0.79

ISSN Imprimir: 0278-940X
ISSN On-line: 1943-619X

Volumes:
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Critical Reviews™ in Biomedical Engineering

DOI: 10.1615/CritRevBiomedEng.v39.i3.30
pages 201-240

Neural Tissue Engineering and Biohybridized Microsystems for Neurobiological Investigation In Vitro (Part 1)

D. Kacy Cullen
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; Penn Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, 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

RESUMO

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 μm), 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.


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