Microfluidic Generation of Composite Biopolymer Microgels with Tunable Compositions and Mechanical Properties

To develop an understanding of the nature of complex, spatiotemporal interactions between cells and the extracellular matrix (ECM), artificial ECMs formed from hydrogels with a particular spectrum of properties are being developed at a rapid pace. We report the microfluidic generation of small, monodisperse composite agarose gelatin hydrogel modules (microgel particles) that can be used for cell encapsulation and can serve as instructive cellular microenvironments. The agarose component of the microgels gelled under reduced temperature, while gelatin modified with phenolic hydroxyl groups underwent peroxidase-catalyzed gelation. Microgel composition, structure, morphology, and rigidity were tuned in a high-throughput manner. The results of this work are important for the generation of libraries of cell-laden polymer microgels for single-cell analysis, tissue engineering, and fundamental studies of the role of local microenvironments in cell fate.