Ribbon-shaped microgels as bioinks for 3D bioprinting of anisotropic tissue structures

Granular microgels are attractive bioinks for bioprinting due to their injectability, printability, modularity, and enhanced macroporosity compared to conventional nanoporous hydrogels. Despite the potential of microgels for bioprinting, most previous work has relied on spherical microgels and produced isotropic tissues, whereas many native tissues are inherently anisotropic. While emerging studies have explored non-spherical microgels for bioprinting, there remains a need for bioinks that support cell alignment and tunable niche cues. Microribbons (μRB) are anisotropic ribbon-shaped microgels, but the potential of μRBs as bioinks for printing 3D anisotropic tissues remains unexplored. Here, we report the development of μRBs with tunable stiffness as bioinks for extrusion-based bioprinting and demonstrate that μRB bioinks maintain excellent printability and align during extrusion. μRB bioinks support alignment of MSCs and endothelial cells, with greater alignment as μRB stiffness increases. Increasing μRB stiffness also accelerates mesenchymal stromal cell osteogenesis in 3D. Finally, we demonstrate the potential of μRB bioinks for modeling breast cancer-bone metastasis, which features spatial patterning of multiple cell types to model cancer cell invasion at the tissue interface. Together, these results establish ribbon-shaped microgels as a new class of anisotropic bioinks, offering a versatile platform to support a broad range of bioprinting applications. • Ribbon-shaped microgels aligned during bioprinting in a stiffness-dependent manner. • Gelatin μRBs were a versatile bioink platform and exhibited rheological characteristics suitable for bioprinting. • Cells oriented along individual μRBs and within organized printed constructs. • μRB bioinks supported stiffness-modulated MSC osteogenesis and multi-tissue cancer-bone modeling.