Organs-on-a-Chip Recapitulating the Gut–Islets Axis for Endocrine Hormone Secretion Regulator Evaluation

Organ-on-a-chip is emerging as a vital platform for in vitro modeling of biological systems. However, its application in the gut–islets axis and assessing regulators of endocrine hormone secretion has yet to be explored. Here, we developed an organ-on-a-chip platform featuring a microfluidic chip with scaffolds of a closed-packed porous structure to recapitulate the characteristics of the gut–islets axis for bile acid (BA) evaluation. The scaffolds were fabricated by negative replication of assembled droplet templates, enabling intestinal L-cells and pancreatic β-cells to form uniform spheroids. The scaffolds were embedded within a well-designed cascading microfluidic chip capable of generating a concentration gradient. Through this, the assessment of different concentrations of BAs in promoting GLP-1 and insulin secretion was achieved, with results consistent with previous studies, indicating the high accuracy of our platform. This novel system holds promise for evaluating other drugs or signaling molecules involved in glucose homeostasis, offering a new avenue for metabolic drug discovery.