Tunable Hydrogel Confinement via On-Chip 3D Printing for Studying Cancer Cell Migration

The
physical confinement of the extracellular matrix (ECM) has
been proven to be a coconspirator in cancer metastasis. However, current
experimental models are limited in accurately dissecting the effect
of mechanical and topographical properties on cancer cell migration
in a confined three-dimensional (3D) environment. In this study, we
propose a facile strategy to produce precisely controlled channel-like
hydrogel confinements on a microfluidic device via a “hydrogel-in-hydrogel”
two-photon 3D printing approach. Within this model, it is demonstrated
that breast cancer cells migrate faster in the stiffer confinements
with an adapted migratory phenotype, and the transcriptomic profile
of the migrating cells shows that the activation of YAP is involved
in this process. This platform allows the fabrication of high-resolution
hydrogel microstructures, real-time observation of the cell–environmental
interplay, and convenient collection of migrating cell samples for
sequencing analyses, which provides a powerful tool for investigating
cell migration and mechanical interactions within a confined microenvironment.