Biomimetic Human Intestinal Tumor‐on‐a‐Chip with Crypts and Villus‐Like Structures for Chemotherapy Drug Evaluations

ABSTRACT Organ‐on‐a‐chip technology holds great value for modeling intestinal tumors. However, how to more accurately replicate the tumor microenvironment and implement high‐throughput drug screening on‐chip remains to be further explored. In this study, we developed a biomimetic intestinal tumor‐on‐a‐chip platform that simulates the 3D structure of intestinal crypts and villi, and incorporates a herringbone fluidic mixer. Compared to conventional chips, this design significantly improves the dynamic interplay between tumor cells and their surrounding microenvironment. Inside the chip, patient‐derived primary epithelial and tumor cells successfully form a 3D tumor model. Furthermore, the platform enables monitoring of dynamic drug response in tumor cells derived from individual patients. Preliminary findings indicate that mitophagy could be a key contributor to the development of chemoresistance. This biomimetic intestinal tumor‐on‐a‐chip platform effectively reproduces the complex characteristics of intestinal tumors through its high‐fidelity 3D structure and dynamic microenvironment.