UC Davis

Neuroinflammation plays a significant role in a wide range of neurological disorders, from neurodegenerative diseases to cancer, affecting millions of people worldwide. As a result, there is a critical need to better understand the mechanisms underlying neuroinflammation and its relationship to different disease states. Organ-on-a-chip platforms can aid in this research by striking a balance between recapitulating relevant cell-cell interactions found in vivo, while reducing the complexity of the system to allow for more controlled mechanistic studies. In this work, we developed an organ-on-a-chip model to study neuroinflammation, with a particular focus on modeling how different disease states are able to propagate to synaptically connected, but anatomically remote regions of the brain. We used theoretical, computational, and experimental methods to optimize a two-chamber microfluidic device to maintain two distinct primary neural cultures that are chemically isolated but synaptically connected. Additionally, we demonstrate the ability to record robust extracellular electrophysiological signals from axons connecting the two cell populations for 60 days in vitro using an integrated surface-patterned microelectrode array. In tandem, we developed and characterized an enhanced cell culture model comprised of neurons, astrocytes, and microglia that more faithfully mimics the in vivo neuroinflammatory response (both neurotoxic and neuroprotective) to a variety of neuroinflammatory stimuli. This “tri-culture” is established and maintained through the use of a specifically designed, serum-free media making the tri-culture particularly amenable to high-throughput experiments and integration into complex culture platforms for studying a wide range of neurological diseases.