Microgel-Based Immunomodulatory Biomaterials for Regulating Macrophage Polarization.

Microgel-based biomaterials have gained increasing attention for their ability to modulate the immune response by regulating macrophage polarization, a key determinant in the transition from inflammation to tissue regeneration. Among these, granular hydrogels, assembled from jammed or annealed microgels, offer unique advantages due to their tunable mechanical properties and inherent interconnected porosity. Compared with many bulk hydrogel systems, granular systems allow modular control of microgel stiffness, degradability, packing density, and pore architecture, enabling controlled macrophage-material interactions. These properties can be engineered to shift macrophage polarization toward pro-regenerative phenotypes, promoting favorable immune environments for tissue repair. Furthermore, the modularity of microgels allows for the incorporation of multiple material types, functional groups, and bioactive cues to guide immune responses. This review discusses current strategies for macrophage modulation using microgel-based systems, focusing on the influence of mechanical and structural design parameters. We highlight recent advances and identify key design considerations for developing next-generation immunomodulatory microgel-based biomaterials for regenerative medicine.