TY - JOUR
T1 - Engineered Axonal Tracts as “Living Electrodes” for Synaptic-Based Modulation of Neural Circuitry
AU - Serruya, Mijail D.
AU - Harris, James P.
AU - Adewole, Dayo O.
AU - Struzyna, Laura A.
AU - Burrell, Justin C.
AU - Nemes, Ashley
AU - Petrov, Dmitriy
AU - Kraft, Reuben H.
AU - Chen, H. Isaac
AU - Wolf, John A.
AU - Cullen, D. Kacy
N1 - Funding Information:
Financial support provided by the National Institutes of Health (U01-NS094340 (D.K.C.) & T32-NS043126 (J.P.H.)), Michael J. Fox Foundation (Therapeutic Pipeline Program #9998 (D.K.C.)), Penn Medicine Neuroscience Center Pilot Award (D.K.C.), Department of Veterans Affairs (Merit Review #B1097-I (D.K.C.), Career Development Award #IK2-RX001479 (J.A.W.), and Career Development Award #IK2-RX002013 (H.I.C.)), National Science Foundation (Graduate Research Fellowships DGE-1321851 (L.A.S. & D.O.A.)), and American Association of Neurological Surgeons and Congress of Neurological Surgeons (2015–2016 Codman Fellowship in Neurotrauma and Critical Care (D.P.)).
Funding Information:
doctoral Bioengineering student in the Cullen Lab at the University of Pennsylvania (Penn). In 2015, he earned a Bachelor’s and Master’s of engineering from Penn in Bioengineering and Robotics, respectively. He was awarded a pre-doctoral Graduate Research Fellowship from the National Science Foundation in 2015, which he has used to further the design and development of a biohybrid neural interface using neural tissue engineering and optogenetics.
Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/3/21
Y1 - 2018/3/21
N2 - Brain–computer interface and neuromodulation strategies relying on penetrating non-organic electrodes/optrodes are limited by an inflammatory foreign body response that ultimately diminishes performance. A novel “biohybrid” strategy is advanced, whereby living neurons, biomaterials, and microelectrode/optical technology are used together to provide a biologically-based vehicle to probe and modulate nervous-system activity. Microtissue engineering techniques are employed to create axon-based “living electrodes”, which are columnar microstructures comprised of neuronal population(s) projecting long axonal tracts within the lumen of a hydrogel designed to chaperone delivery into the brain. Upon microinjection, the axonal segment penetrates to prescribed depth for synaptic integration with local host neurons, with the perikaryal segment remaining externalized below conforming electrical–optical arrays. In this paradigm, only the biological component ultimately remains in the brain, potentially attenuating a chronic foreign-body response. Axon-based living electrodes are constructed using multiple neuronal subtypes, each with differential capacity to stimulate, inhibit, and/or modulate neural circuitry based on specificity uniquely afforded by synaptic integration, yet ultimately computer controlled by optical/electrical components on the brain surface. Current efforts are assessing the efficacy of this biohybrid interface for targeted, synaptic-based neuromodulation, and the specificity, spatial density and long-term fidelity versus conventional microelectronic or optical substrates alone.
AB - Brain–computer interface and neuromodulation strategies relying on penetrating non-organic electrodes/optrodes are limited by an inflammatory foreign body response that ultimately diminishes performance. A novel “biohybrid” strategy is advanced, whereby living neurons, biomaterials, and microelectrode/optical technology are used together to provide a biologically-based vehicle to probe and modulate nervous-system activity. Microtissue engineering techniques are employed to create axon-based “living electrodes”, which are columnar microstructures comprised of neuronal population(s) projecting long axonal tracts within the lumen of a hydrogel designed to chaperone delivery into the brain. Upon microinjection, the axonal segment penetrates to prescribed depth for synaptic integration with local host neurons, with the perikaryal segment remaining externalized below conforming electrical–optical arrays. In this paradigm, only the biological component ultimately remains in the brain, potentially attenuating a chronic foreign-body response. Axon-based living electrodes are constructed using multiple neuronal subtypes, each with differential capacity to stimulate, inhibit, and/or modulate neural circuitry based on specificity uniquely afforded by synaptic integration, yet ultimately computer controlled by optical/electrical components on the brain surface. Current efforts are assessing the efficacy of this biohybrid interface for targeted, synaptic-based neuromodulation, and the specificity, spatial density and long-term fidelity versus conventional microelectronic or optical substrates alone.
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U2 - 10.1002/adfm.201701183
DO - 10.1002/adfm.201701183
M3 - Article
AN - SCOPUS:85028731639
SN - 1616-301X
VL - 28
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 12
M1 - 1701183
ER -