(178x) Gelatin Methacryloyl Granular Hydrogel Bioinks for in-Situ Bioprinting

Gelatin methacryloyl (GelMA) is a widely used biomaterial to partially mimic the extracellular matrix (ECM), promote cell activities, and enable tissue regeneration. Its crosslinkable functional groups allow for tunable mechanical properties, making it suitable for various tissue engineering applications. However, GelMA as a bulk (nanoporous) hydrogel faces structural limitations in biofabrication due to the inherent coupling of stiffness and porosity. GelMA hydrogel microparticles (microgels) may be used as building blocks of granular bioinks, which enhance cell infiltration and viability as a result of porosity. Despite these advantages, physically crosslinked GelMA microgels must be maintained below the melting point for stability, limiting their potential for in situ fabrication at the physiological temperature (37 °C). Here, we develop thermostable GelMA microgels paired with heterogeneously charged nanoparticles (NPs) to make GelMA granular bioinks, capable of in situ forming porous scaffolds via extrusion bioprinting. GelMA microgels were fabricated using a step emulsification microfluidic device and stabilized through partial photocrosslinking, rendering them stable at the physiological temperature while maintaining enough unreacted vinyl groups to form stable crosslinked structures after 3D bioprinting. Interfacial NP self-assembly enhances microgel-microgel interactions, yielding a shear thinning composite granular bioink. This platform enables the in situ biofabrication of porous GelMA hydrogel scaffolds, which may be used for regenerative engineering.