Abstract
For implantable neural interfaces, the functional and clinical outcomes of inorganic microelectrodes are challenged by limitations in specificity and long-term performance. A biological intermediary between micro-electrical devices and the brain may improve specificity and longevity through (1) natural synaptic integration with deep neural circuitry, (2) accessibility on the brain surface, (3) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable “living electrodes”, living cortical neurons and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex as an in vivo proof-of-concept for this neural interface paradigm. The creation and characterization of these functional, optically-controllable “living electrodes” are critical steps in developing a new class of optobiological tools for neural interfacing.
Competing Interest Statement
D.K.C. is a co-founder of two University of Pennsylvania spin-out companies related to nervous system regeneration and restoration: INNERVACE, Inc. and Axonova Medical, LLC. There are two patent applications related to the methods, composition, and use of micro-tissue engineered neural networks, including U.S. Patent App. 15/032,677 titled ''Neuronal replacement and reestablishment of axonal connections'' (D.K.C.) and U.S. Patent App. 16/093,036 titled ''Implantable living electrodes and methods for use thereof'' (D.K.C., J.P.H., J.A.W., H.I.C., and M.D.S.). The other authors declare that they have no competing interests.
Footnotes
Final revision provides additional histological insights into the living electrode performance post-transplant, as well as developmental considerations for in vitro modeling and validation versus more long-term clinical translation.