TY - JOUR T1 - Development of Optically-Controlled “Living Electrodes” with Long-Projecting Axon Tracts for a Synaptic Brain-Machine Interface JF - bioRxiv DO - 10.1101/333526 SP - 333526 AU - Dayo O. Adewole AU - Laura A. Struzyna AU - James P. Harris AU - Ashley D. Nemes AU - Justin C. Burrell AU - Dmitriy Petrov AU - Reuben H. Kraft AU - H. Isaac Chen AU - Mijail D. Serruya AU - John A. Wolf AU - D. Kacy Cullen Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/06/333526.abstract N2 - Achievements in intracortical neural interfaces are compromised by limitations in specificity and long-term performance. A biological intermediary between devices and the brain may offer improved specificity and longevity through natural synaptic integration with deep neural circuitry, while being accessible on the brain surface for optical read-out/control. Accordingly, we have developed the first “living electrodes” comprised of implantable axonal tracts protected within soft hydrogel cylinders for the biologically-mediated monitoring/modulation of brain activity. Here we demonstrate the controlled fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of neuronal activity within these engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex in vivo as a proof-of-concept for this neural interface paradigm. The creation and functional validation of these preformed, axon-based “living electrodes” is a critical step towards developing a new class of biohybrid neural interfaces to probe and modulate native circuitry.Competing Interest StatementD.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. ER -