Bio-inspired 3D bioelectronic model of the intestinal crypts

Organ-on-a-chip (OOC) technology represents an important tool in the field of molecular biology, offering a platform that mimics the complex structure and function of human organs in a controlled laboratory setting. These systems have the potential to host biologically complex 3D cell co-cultures, allowing researchers to study cellular behavior in a more physiologically relevant environment compared to traditional 2D models. Due to their ability to closely mimic human physiology, these systems are rapidly gaining popularity, as they exhibit high predictive power for clinical outcomes and may one day replace the use of animal models. The central aim of the proposed project is to increase the biological complexity of bioelectronic intestine-on-a-chip models by incorporating the tissue structures, cell types, and microbes essential for healthy gut function. The first objective is to 3D print a conductive polymer scaffold that recapitulates the 3D structure of colonic crypts and the microporous architecture of the extracellular matrix. This scaffold will be integrated into the E-transmembrane, a device developed by the Owens group at the University of Cambridge, and validated using a cell line model of the intestinal epithelium. The second objective involves replacing the cell lines with dissociated primary intestinal organoids on the 3D scaffold to achieve the epithelial cellular diversity of the gut and form a stem cell niche at the base of the crypts. Finally, human whipworm will be introduced into the model to further understand parasitic infections in the gut. Through the combination of molecular assays, imaging techniques, and electrical measurements, insights will be gained into the complex interactions between cells, parasites, and biomaterials within the OOC system. Overall, this project aims to advance the capabilities of OOC technology for studying gut physiology, disease mechanisms, and drug responses in a more physiologically relevant context.