Microfluidic Bi-Axial Cell Stretching Platform for Intestinal Epithelial Cell Modeling

Abstract Intestinal epithelial cells encounter intricate mechanical and physiological stimuli within the intestinal microenvironment. Establishing a precise and dynamic in vitro model is essential to exert control over cellular behaviors. As microfluidic devices offer unparalleled versatility and precision for replicating physiological conditions, this tool has attracted increasing attention in broad applications. This study presents a novel microfluidic bi-axial 9-well cell stretching system designed for cells using two common intestinal epithelial cell lines (Caco2 and HT29) as the models. The system employs a mechanical linkage system capable of simultaneously stretching cells in nine wells, applying a 10% strain driven by a linear actuator. Realtime strain data is collected on the shaft to validate displacement and detect system motion disturbances. The material characterization of 15:1 polydimethylsiloxane was done utilizing a tensile testing system, and the experimental validation was achieved through digital image correlation. Cellular morphology and viability were assessed under different cell culture conditions for 5 days. The results indicate that cells cultured in stretching and static conditions exhibited higher viability compared to those solely cultured under flow conditions. Interestingly, both cell lines demonstrated faster differentiation under flowing and stretching conditions, displaying an enlarged cellular membrane. HT29 cells also exhibited higher viability than Caco2 cells under cell stretching. Furthermore, flow shear stress reduced the viability of both cell lines emphasizing the need for further comprehensive studies to conduct a parametric analysis of flow shear stress and strain rate to optimize dynamic cell culturing conditions to obtain desired cellular properties.