Bioprinted gut-on-a-chip to mimic the small intestinal mucosa

Abstract

Organ-on-a-chip (OoC) is an emerging technology which combines microfluidics with cell culture to create platforms that replicate human organs. These predictive models are used to understand human physiology and to predict responses to medical treatments. Being the small intestine the largest interface between the environment and the human organism and one of the most important organs involved in drug metabolism, there is an increasing interest from researchers and the pharmaceutical industry for reliable in vitro intestine models. However, currently available gut-ona- chip devices that replicate the complex microenvironment found in the in vivo tissue are scarce, limiting their translational capabilities to clinical outcomes. Therefore, in this work we aim to develop a reproducible gut-on-a-chip device that mimics the 3D architecture and cell heterogeneity of the small intestinal mucosa. SLA 3D bioprinting will be used to fabricate cell-encapsulating GelMAPEGDA hydrogels that support the formation of an epithelial monolayer on top, to replicate the two compartments of the intestinal mucosa; the lamina propria and the intestinal epithelial barrier. The hydrogels contain fibroblasts and immune cells, which play a key role in maintaining the intestinal mucosa integrity and homeostasis. These scaffolds will be then incorporated into PDMS microfluidic chips to create the final biomimetic system. Although further improvements are needed, this gut-on-a-chip, obtained using precise and fast fabrication techniques, might be a useful tool for drug development and human physiology studies.