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

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.