Development of optically controlled “living electrodes” with long-projecting axon tracts for a synaptic brain-machine interface

Abstract

For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) 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.

Recent advances in materials and applications for bioelectronic and biorobotic systems

“…The electrodes accurately performed optical sensing and neuromodulation in the rat brain for extended periods. 61 In the future, living electrodes may be combined with traditional electronic circuits to create a closedloop neural interfaces. Additionally, biological vasculature, which may increase biointegration and cell viability near implants, should be considered in future bioelectronic and biorobotic systems.…”

Carbohydrate based biomaterials for neural interface applications

“…97,98 Additionally, these approaches can be combined with multi-electrode systems to enable recording and stimulation while promoting the regeneration of the tissue surrounding the implanted device. 18,99,100…”

“…6(G–I)) seeded with neurons on one end were demonstrated as conduits that can be implanted in the brain to establish bi-directional communication with the host tissue. 18,293 These strategies can inspire biohybrid multi-modal applications which combine electrical elements with biocompatible components to promote seamless integration with the tissue.…”

Advances in construction and modeling of functional neural circuits in vitro

“…We call these connected organoids "connectoids". The interorganoid connection could be also formed by connecting two organoids with reciprocally extending axons within a tube of gel [120,121].…”