Gel-Shrink Softlithography: Enabling 3D Tissue Culture Microstructure Miniaturization and Tacky Super-Soft Material Molding

In this study, we introduce an innovative hydrogel soft lithography technique that leverages the significant volume change of hydrogels during hydration. Through a systematic desiccation process applied to hydrogels containing microfeatures, we achieved a remarkable 2-fold reduction in feature dimensions. These shrunken hydrogel structures were then readily molded using standard soft lithography methods. Furthermore, we demonstrated the techniques utility in rectifying surface imperfections commonly found in 3D printed structures, offering promising prospects in fields like tissue engineering. Additionally, our study discovered a unique capability of hydrated hydrogel molds in molding super-soft, tacky elastomeric materials, exemplified by CY25-276 and low cross-linker ratio PDMS. This development opens doors to studying cellular forces through traction force microscopy to a broader spectrum of 3D structural contexts. In support of our efforts in microfabrication advancement, we explored multicellular responses to surface curvatures of diminishing dimensions. Our findings reveal a curvature-dependent alignment pattern: cells residing on convex surfaces align with the direction of least curvature, while those in concave regions align with the direction of the strongest curvature. These results underscore the critical influence of geometric complexity in biological systems and highlight the need for continuously improving methods to replicate geometric qualities relevant to these environments.