Engineered Axonal Tracts as “Living Electrodes” for Synaptic-Based Modulation of Neural Circuitry

M. D. Serruya, J. P. Harris, D. O. Adewole, L. A. Struzyna, J. C. Burrell, A. D. Nemes, D. Petrov, R. H. Kraft, H. I. Chen, J. A. Wolf, D. K. Cullen, Adv. Funct. Mater. 2017, doi:10.1002/adfm.201701183

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.

Friedrich’s ataxia: Patients develop severe motor impairments in the absence of pro­prioceptive and epicritic signals from the periphery. Living electrodes could provide an articial sensory arc: by tapping into signals from periphery (such as strain gauges, accelero­meters and gyroscopes worn at joints in all four limbs, or from implanted cuff recordings of peripheral nerves), living electrodes implanted into primary sensory cortices could pro­vide sensory feedback and allow improved voluntary move­ ment and functional independence. Grown with glutamatergic neurons, these living electrodes could be implanted to termi­nate in layer IV of the post­central gyrus; because living elec­trodes are themselves quite small, multiple constructs could be implanted corresponding to different joints (e.g., gyros from the left knee driving a living electrode implanted in the right medial sensory cortex, left elbow and shoulder to right lateral sensory cortex, and viceversa for the right extremities and left hemisphere).