Gut-on-a-Chip-Based Real-Time miRNA-21 Monitoring and Anti-Inflammatory Drug Evaluation.

Abstract

MiRNA-21 is a crucial biomarker involved in inflammatory pathways and is linked to gastrointestinal diseases like inflammatory bowel disease (IBD). Its dynamic expression reflects disease progression and treatment response, making it an attractive target for diagnostic and therapeutic applications. However, current in vitro models often lack the physiological relevance needed for effective biomarker monitoring, limiting their utility in drug screening and therapeutic evaluation. In this study, we developed an advanced gut-on-a-chip (GOC) platform integrated with an electrochemical biosensor to achieve high-sensitivity detection of miRNA-21. The chip replicates key aspects of the intestinal microenvironment, including dynamic medium perfusion and mechanical stretching, which support the formation of a functional intestinal barrier using Caco-2 cells. The integrated biosensor demonstrated excellent performance, with a wide linear range from 1 × 10-15 to 1 × 10-10 M, enabling precise monitoring of miRNA-21 expression. To demonstrate its utility, we established an in vitro inflammation model by introducing pro-inflammatory stimuli and monitored miRNA-21 levels dynamically. The platform successfully captured the correlation between miRNA-21 expression and inflammatory progression. Furthermore, we used the system to evaluate the effects of anti-inflammatory drugs, providing proof-of-concept for its application in drug screening.