Jouybar, M. | bioRxiv Science

bioRxiv2025

A breast Duct-on-Chip model for emulating invasive ductal carcinoma and testing therapies

There are not many in vitro models that closely mimic ductal carcinoma in vivo. We present a novel breast duct-on-chip model designed to simulate ductal carcinoma in situ as well as invasive breast ductal carcinoma. This model features a tubular channel encapsulated in collagen and lined with normal epithelial cells. A basement membrane layer forms between the epithelium and the collagen, expressing basement membrane proteins. Invasive breast cancer cell lines are introduced into the breast duct to simulate ductal carcinoma. We observe two distinct lateral migration regimes that depend on the initial number of cancer cells within the duct. Additionally, the morphology of the breast duct and the invasion distance varies between the two regimes. Furthermore, we examine the effects of two widely used chemotherapies, Doxorubicin and Paclitaxel, on the invasion behavior of breast cancer cells within this model. The introduction of these drugs alters the invasion patterns of cancer cells, with Paclitaxel inhibiting invasion in 30% of tests. Notably, in the absence of treatment, all tests result in single-cell invasion. Our findings also highlight the dynamics of intraductal migration of cancer cells in non-invasive DCIS, revealing flow-like movements of cancer cells along the epithelial layer. This work establishes a valuable platform for investigating the mechanisms of cancer invasion from the epithelium and basement membrane, as well as evaluating chemotherapeutic strategies and testing novel cell-based therapies. It can have significant implications for understanding the dynamics of early-stage ductal carcinoma for improving treatment protocols of existing chemotherapies, and for developing and advancing novel therapies.

bioengineering↗

bioRxiv2024

The impact of channel geometry and flow regime on endothelial orientation and morphology in vessel-on-chip

This study investigates the impact of channel geometry and applied flow on the morphology and function of endothelial cells (ECs) within vessel-on-chip (VoC) models. Traditional organ-on-chip models often utilize rectangular cross-section channels, resulting in flat walls, sharp corners, and non-uniform wall shear stress profiles, which do not accurately mimic physiological conditions. Tubular channels with a circular cross-section provide a more in vivo-like geometry and result in a physiological uniform wall shear stress. Here, sugar 3D-printing is used for fabricating tubular channels, and stereolithography 3D-printing is applied for making rectangular channels. Using these models, the effects of both channel geometry and various flow conditions on the orientation and morphology of ECs, from both blood and lymph vessels, is explored. The research demonstrates that ECs in tubular channels exhibit a more uniform coverage and circumferential alignment/migration compared to rectangular channels. Unidirectional and bidirectional flow conditions induce alignments parallel to flow, overruling the circumferential alignment induced by curvature in tubular channels. The combination of tubular geometry and pulsatile flow induces enhanced circumferential orientation, different from rectangular channels in which cells remain primarily aligned along the flow direction under pulsatile flow. In summary, our systematic study shows that the channel curvature determines the cell orientation in static conditions, and that adding flow results in a competing effect between geometry and flow for which the resulting cell alignment depends on the flow conditions. Additionally, the study examines the initial adhesive interactions between monocytes and ECs, revealing that EC orientation induced by different flow regimes impacts monocyte rolling velocities. This finding is important for understanding immune cell motility and adhesion in healthy and diseased states. This study underlines the importance of the combined effect of channel geometry and flow conditions in VoC models, and it provides a strong motivation for the continued development of advanced OoC systems with ever more representative geometrical designs and flow control, to maximize the potential of OoC to revolutionize biomedical research and personalized medicine by providing more accurate and functional models of human physiology.

bioengineering↗