Reactive Multifunctional Ink for Hydrogel Fabrication and Cell-Laden 3D Printing via Incorporation of Strontium-Doped...

Three-dimensional printing offers a powerful strategy for transformation of hydrogels into multifunctional scaffolds that can support cell growth and tissue regeneration. Here, we report a photo-crosslinkable gelatin and silk-based reactive ink that can be utilized for production of bulk hydrogels in addition to an additive manufacturing-enabled three-dimensional construct for osteoblast growth. The ink is engineered to provide dual therapeutic functionalities through (1) strontium ion delivery from dispersed strontium-doped bioactive glass (Sr-BG) and (2) the presence of active thiol groups post crosslinking that enables post-production modification/functionalization of the hydrogels through the thiol handle. Here, Sr-BG provides therapeutic levels of strontium ion release, supporting osteoblast growth within the hydrogel matrix. The proposed ink exhibits shear-thinning behavior conducive to extrusion-based bioprinting, enabling fabrication of cell-laden constructs that recapitulate complex tissue architectures. Printed Sr-BG-containing hydrogels support osteoblast metabolic activity over 7 days, attributed to synergistic effects of strontium-mediated signaling and a favorable matrix environment. Finally, this work extends nitrosation of active thiol groups as a pilot study for utilization of thiols post-production to produce antimicrobial hydrogels that demonstrated ∼83% reduction in viability of Staphylococcus aureus and ∼92% reduction with Escherichia coli when compared to non-functionalized controls. Collectively, this reactive ink provides a unique platform for production of bulk and cell-laden 3D-printed hydrogels in addition to the prospect of countless applications through post-production thiol modification.