title: 3D printed nervous system on a chip.
abstract: Bioinspired organ-level in vitro platforms are emerging as effective technologies for fundamental research, drug discovery, and personalized healthcare. In particular, models for nervous system research are especially important, due to the complexity of neurological phenomena and challenges associated with developing targeted treatment of neurological disorders. Here we introduce an additive manufacturing-based approach in the form of a bioinspired, customizable 3D printed nervous system on a chip (3DNSC) for the study of viral infection in the nervous system. Micro-extrusion 3D printing strategies enabled the assembly of biomimetic scaffold components (microchannels and compartmented chambers) for the alignment of axonal networks and spatial organization of cellular components. Physiologically relevant studies of nervous system infection using the multiscale biomimetic device demonstrated the functionality of the in vitro platform. We found that Schwann cells participate in axon-to-cell viral spread but appear refractory to infection, exhibiting a multiplicity of infection (MOI) of 1.4 genomes per cell. These results suggest that 3D printing is a valuable approach for the prototyping of a customized model nervous system on a chip technology.
authors.affiliation: Department of Industrial and Systems Engineering, Virginia Tech, Blacksburg, Virginia 24061, USA and Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Blake N
authors.initials: BN
authors.lastname: Johnson
authors.affiliation: Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Karen Z
authors.initials: KZ
authors.lastname: Lancaster
authors.affiliation: Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hogue
authors.affiliation: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA and Department of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA. mcalpine@umn.edu.
authors.forename: Fanben
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Yong Lin
authors.initials: YL
authors.lastname: Kong
authors.affiliation: Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Lynn W
authors.initials: LW
authors.lastname: Enquist
authors.affiliation: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA and Department of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA. mcalpine@umn.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: McAlpine
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000295:instrumentation*; D056656:Lab-On-A-Chip Devices; D009420:Nervous System / Q000166:cytology / Q000821:virology; D066330:Printing, Three-Dimensional / Q000295:instrumentation*; D051381:Rats