Investigating Hepatic Glucose Metabolism in Insulin Resistance Cell Model Using 3D‐Printed Open Microfluidic Chip

The liver is recognized as a pivotal tissue contributing to insulin resistance and exerts a crucial influence on the systemic orchestration of glucose metabolism. While biologists have embraced microfluidics for its potential to elucidate hepatic glucose homeostasis and metabolic dynamics, huge challenges remain in the widespread adoption of microfluidic devices, such as complex design and production, and the use of additional pumps for fluid handling. In this study, we report the fabrication of an α-cellulose-modified open microfluidic chip using a 3D printer for the investigation of glucose metabolism in HepG2 cells after insulin and pioglitazone intervention. The Christmas tree-inspired design of the chip integrates a concentration gradient generation zone alongside a 3D cell culture environment. The chip's utility was assessed through the measurement of cellular glucose uptake and ROS expression levels, revealing that the 3D cell model exhibited markedly reduced sensitivity to insulin and pioglitazone compared to the 2D model. Additionally, expression of insulin resistance-related proteins was examined to confirm the improvement of insulin resistance. Collectively, these findings underscore the chip's capacity for stable fluid management and utility in advancing glucose metabolism research. Moreover, this approach provides the new strategy for the development of disease cell models to explore the physiological and pathophysiological intricacies underpinning metabolic disorders.