How does microsystem geometry affect hydrogel docking and cell culture?

Microfluidic systems incorporating hydrogels are widely used in in vitro tissue modeling to recreate three-dimensional (3D) microenvironments resembling the native extracellular matrix. However, hydrogel behavior in microsystems is strongly dependent on device geometry, which affects hydrogel confinement, stability, mass transport, and subsequent cell responses. In this study, we systematically investigated the influence of microsystem architecture on hydrogel docking, diffusion, and cell culture performance using two confinement strategies: pillar-based and ladder-based geometries. Collagen (type 1) and fibrin hydrogels were used to evaluate the influence of geometric parameters and hydrogel mechanical properties. In pillar-based geometries, the spacing between microstructures governs hydrogel retention, and inappropriate spacing leads to reduced stability. Ladder geometries supported stable localization of stiffer collagen, while softer fibrin was less suitable for this configuration. Diffusion analysis conducted before cell seeding demonstrated geometry-dependent transport characteristics and the formation of concentration gradients. These physical factors were reflected in cell behavior, as both the hydrogel type and the microsystem geometry affected cell morphology and viability. Overall, the results emphasize the role of microsystem geometry in the performance of hydrogel-based cultures and provide general design considerations for improving the robustness and reproducibility of microfluidic tissue models.