Biphasic microgel-based bioinks with balanced printability, mechanical stability, and cytocompatibility for extrusion-based bioprinting.

A primary challenge in extrusion-based bioprinting using microgel-based bioink is balancing printability, mechanical stability, and biological functionality. In this study, we developed a microgel-based biphasic bioink that leverages microgels' advantages while maintaining porosity to enhance cellular performance. This biphasic bioink consists of densely packed physically crosslinked silk acid-based microgels (SA-MG) suspended in a secondary hydrogel precursor of alginate/carboxymethyl cellulose (Alg/CMC), which crosslinks physically after printing. The resulting dynamic, hybrid matrix enhances ink cohesion during extrusion, enabling the high-fidelity fabrication of complex, spatially controlled heterogeneous 3D structures with tunable mechanical properties. Cells cultured in the biphasic system exhibit significantly enhanced proliferation, demonstrating good cytocompatibility and early signs of vascularization. This approach represents a significant advance in biofabrication of 3D printing mechanically robust scaffolds.