Integration of reconfigurable microchannels into aligned three-dimensional neural networks for spatially controllable neuromodulation | Science Advances

Anisotropically organized neural networks are indispensable routes for functional connectivity in the brain, which remains largely unknown. While prevailing animal models require additional preparation and stimulation-applying devices and have exhibited limited capabilities regarding localized stimulation, no in vitro platform exists that permits spatiotemporal control of chemo-stimulation in anisotropic three-dimensional (3D) neural networks. We present the integration of microchannels seamlessly into a fibril-aligned 3D scaffold by adapting a single fabrication principle. We investigated the underlying physics of elastic microchannels’ ridges and interfacial sol-gel transition of collagen under compression to determine a critical window of geometry and strain. We demonstrated the spatiotemporally resolved neuromodulation in an aligned 3D neural network by local deliveries of KCl and Ca ²⁺ signal inhibitors, such as tetrodotoxin, nifedipine, and mibefradil, and also visualized Ca ²⁺ signal propagation with a speed of ~3.7 μ m/s. We anticipate that our technology will pave the way to elucidate functional connectivity and neurological diseases associated with transsynaptic propagation.