Anisotropic Hydrogel Degradation Enhances 3D Collective Cell Alignment, Mechanotransduction and Osteogenic Differentiation

In addition, we observe a boosted osteogenic differentiation when compared to single-phase materials, as mid osteogenic markers (osteocalcin) are expressed at day 14 in anisotropic gels, whereas in single-phase only early osteogenic markers are found (osterix). Mechanosensing pathways were evaluated using the expression and localization of YAP. Deg sections in patterned materials have an enhanced nuclear translocation and higher YAP expression compared to single-phase Deg materials and noDeg sections.

This effect is lost and no patterns in YAP expression and localization emerge when using an MMP-scramble peptide or no-RGD materials. These findings demonstrate that 3D patterns in alginate hydrogel degradation guide hMSC spreading, collective alignment, enhance YAP nuclear translocation and osteogenic differentiation. Mimicking tissue anisotropy in 3D patterned hydrogels could have broad applications in biofabrication and tissue engineering.