Spatially Controlled Release from Printable Microgels for Embedded Bioprinting

Abstract Granular hydrogels composed of jammed microgels have emerged as promising biomaterials for 3D bioprinting due to their tunable viscoelastic properties and ability to incorporate bioactive molecules and encapsulate cells within the interstitial spaces between the particles. Here, we present a new strategy to achieve spatially controlled release of bioactive molecules using κ-carrageenan microgels having a triple role as a printable bioink, a supportive matrix, and a carrier for bioactive molecules. To enable molecule incorporation, we employed a freeze-drying and absorption loading technique and demonstrated that trehalose preserves microgel morphology and rheological properties. Release kinetics of small (fluorescein) and large (BSA) model molecules revealed sustained diffusion-driven release. The microgels retained their printability and flow properties after rehydration and enabled precise printing within a granular support material. As a proof of concept, we directed human adipose-derived mesenchymal stem cell (hADMSC) differentiation into adipocytes by printing microgels loaded with an adipogenic medium at distinct regions within the support material. Differentiation was confirmed via lipid droplet staining and quantitative analysis. A significantly greater lipid accumulation was observed in hADMSC constructs located within defined, spatially patterned ADP-loaded microgels compared with constructs located in the surrounding region. Our findings demonstrate the potential of this platform for engineering complex, multicellular constructs with region-specific biochemical microenvironments through embedded bioprinting.