Parameter studies for highly concentrated spheroid printing considering nozzle clogging and printing resolution with two-way coupled fluid-particle simulations

Spheroid-based bioprinting is essential for reproducing high-cell-density tissues where cell–cell interactions are critical, such as pancreatic tissue. Although spheroids more effectively mimic the in vivo microenvironment compared to conventional culture systems, nozzle clogging remains a major technical challenge that compromises printing resolution and consistency. In this study, we integrated two-way coupled fluid-particle simulations with experimental validation to systematically analyze key factors influencing clogging and resolution stability in high-concentration spheroid printing. Using pancreatic-derived extracellular matrix (pdECM)-based bioink, we analyzed wall shear stress (WSS) and relative velocity distributions under various nozzle geometries and pneumatic conditions. PDMS molding techniques were applied to visualise internal nozzle structures, enabling precise comparisons between experimental and simulation results. Tapered nozzles, particularly 25G and 22G configurations, exhibited more uniform flow characteristics than cylindrical nozzles of equivalent gauge, resulting in reduced shear stress and minimised spheroid aggregation near the nozzle outlet. Optimised nozzle geometry and pneumatic control promoted uniform spheroid distribution while maintaining structural integrity. Notably, the 25G tapered nozzle maintained comparable printing resolution to the 24G cylindrical nozzle while demonstrating significantly more stable extrusion with reduced clogging risk, confirming that nozzle geometry optimisation can simultaneously address both resolution and clogging challenges.