A Computational Approach for Biomimetic Design of Liver‐On‐A‐Chip

In this study, we present a biomimetic liver‐on‐a‐chip (LOC) device inspired by the structural organisation of the hepatic acinus and developed through COMSOL Multiphysics simulation. The design incorporates antiparallel perfusion channels and microchannel barriers to mimic nutrient delivery and bile drainage in the liver, while maintaining physiologically relevant low shear stress conditions suitable for hepatocyte culture. A truncated LOC model was first used to explore pressure, shear stress, and concentration distributions, revealing that media perfusion minimally perturbs the cell region while bile flow significantly impacts nutrient diffusion. Full‐scale simulations were then performed, demonstrating key discrepancies with the truncated model due to length‐dependent diffusion effects, emphasising the importance of simulating full geometries in transport‐limited systems. The model was validated experimentally with dye‐based flow studies and HepG2 cell culture under dynamic perfusion. Functional validation confirmed that the LOC supports directional solute gradients and cell growth under controlled shear. This integrated in silico–in vitro approach provides a robust framework for the design of organ‐on‐a‐chip systems, reducing development cycles and improving physiological relevance for drug testing and liver disease modelling.