The Impact of Channel Geometry and Flow Regime on Endothelial Orientation and Morphology in Vessel‐on‐Chip

Abstract This study investigates the impact of channel geometry and applied flow on the orientation and morphology 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 circular cross‐sections provide a more in vivo‐like geometry and result in a physiological uniform wall shear stress. Here, tubular channels fabricated using sugar 3D‐printing are compared with rectangular channels made via stereolithography 3Dprinting. The results show that ECs from both blood and lymph vessels exhibit more uniform coverage and circumferential alignment in tubular channels than in rectangular channels. Unidirectional or bidirectional flow conditions align ECs parallel to the flow, overruling the circumferential alignment induced by curvature in tubular channels. Pulsatile flow enhances circumferential orientation in tubular channels, while alignment along the flow is maintained in rectangular channels. Additionally, EC orientation induced by flow impacts monocyte rolling velocities, crucial for understanding immune cell motility. This study underlines the importance of the combined effect of channel geometry and flow conditions in VoC models, and advocates for the continued development of advanced organ‐on‐chip systems that better replicate human physiology.