Organ-on-a-Chip (OOC) platforms are microfluidic systems that recreate key features of human organ physiology in vitro via controlled perfusion. Fluid mechanical stimuli strongly influence cell morphology and function, making this important for cardiovascular OOC applications exposed to pulsatile blood flow. However, many existing OOC devices employ relatively simple chamber geometries and steady inflow assumptions, which may cause non-uniform shear exposure to cells, create stagnant regions with prolonged residence time, and overlook the specific effects of pulsatile perfusion. Here, we used computational fluid dynamics (CFD) to investigate how chamber geometry and inflow conditions shape the near-wall flow environment on a cell culture surface at a matched cycle-averaged volumetric flow rate. Numerical results demonstrated that pillarized chambers markedly reduced relative residence time (RRT) versus the flat chamber, and the small pillar configuration produced the most uniform time-averaged wall shear stress (TAWSS) distribution among the tested designs. Phase-resolved analysis further showed that wall shear stress varies with waveform phase, indicating that steady inflow may not capture features of pulsatile perfusion. These findings provide practical guidance for pillar geometries and perfusion conditions to create more controlled and physiologically relevant microenvironments in OOC platforms, thus improving the reliability of cell experimental readouts.
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