(432b) Engineered Models of the Gut-Brain Axis

The gut-brain-axis is a complex bi-directional communication pathway between the gastrointestinal tract, the enteric nervous system (ENS), and the central nervous system (CNS) that is implicated in not only gastrointestinal function, but also cognitive tasks like memory and decision making. Gastrointestinal flora has also been implicated in alterations of brain function and behavior, however, mechanisms behind the gut-to-brain communication remain poorly understood. To investigate the mechanisms for epithelial/neural interactions in the gastrointestinal tract and understand the impact of alterations in neural activity in response to intestinal contents, we are developing in vitro humanized culture models of the enteric-gut axis. These platforms, termed “Organs-on-chips,” have generated interest from academia and industry as these physiological models may augment drug and basic biological discoveries. However, the lack of rapid, scalable, and facile manufacturing techniques may limit the widespread use of organs-on-chips. Here I will discuss a novel laser-cut and assembly-based fabrication method for simple, and cost-effective thermoplastic organ-chips. It has also been proposed that seeding patient derived cells will enable personalized medicine, but current intestine-on-a-chip models utilize immortalized cells and do not include support cells such as enteric neurons. Finally, I will discuss the culture and differentiation of a primary, human epithelial monolayer from intestinal organoids for future on chip studies that recapitulate the heterogeneous gut population, and the impact of trophic cross-talk between the epithelium and enteric populations in static models.