Hydrogel-based drug delivery systems hold significant clinical potential by enabling precise spatial and temporal control over therapeutic release, ranging from metabolites, macromolecules to other cellular and subcellular constructs. However, achieving programmable release of payloads with diverse molecular weights at distinct rates typically require complex polymer designs that can compromise the accessibility and biocompatibility of the delivery system. We present a scalable method for producing injectable, micrometer-scale alginate hydrogel particles (microgels) with precisely tuned microstructures for multiplexed, programmable cargo release. Our approach integrates an established jetting technique with a simple post-synthesis ion-exchange process to fine-tune the crosslinked microstructure of alginate microgels. By varying cation type (Ca2+, Mg2+, Na+) and concentration, we systematically modulate the microgels’ chemical and physical properties to control release rates of model compounds, including rhodamine B, methylene blue, and dextrans of various molecular weights. Additionally, a PEG-alginate composite microgel system is used to demonstrate stepwise multiplex drug release of rhodamine B. These findings offer a straightforward strategy for post-synthetic manipulation of ionic microgels with controllable release performances, paving the way for advanced biomedical applications.
