Microgel-mediated organoid engineering: Biomaterial design, microenvironmental regulation, and biofabrication strategies

Organoids are organ-like structures formed by the self-organization of stem cells, progenitor cells, or patient-derived cells within a three-dimensional (3D) microenvironment. They are capable of mimicking the cellular composition, spatial structure, and functional characteristics of in situ tissues. Organoids have become an important platform for developmental biology, disease modeling, drug screening, and regenerative medicine. However, current organoid culture remains highly dependent on animal-derived matrices. The poorly defined composition, substantial batch-to-batch variability, and limited tunability of the mechanical and degradation properties of these matrices hinder the clinical translation of organoid models. Microgels typically refer to micrometer-scale hydrogel particles (1–1,000 μm) formed by the crosslinking of natural or synthetic polymers. Compared to traditional bulk hydrogels, microgels combine the design flexibility of individual particles with their collective ability to assemble into larger structures. By adjusting the size, stiffness, porosity, surface ligands, degradation rates, and factor release behavior of microgels, they can provide cells with a more controllable local microenvironment. This review focuses on the fundamental material properties, structural characteristics, fabrication techniques, and functional mechanisms of microgels in organoid engineering. It discusses their applications as cell-encapsulation units, scaffold templates, self-assembling building blocks, and bioactive-factor delivery platforms and evaluates their potential for standardized and scalable organoid manufacturing. Finally, we summarize the key challenges facing the field and outline the future directions for stimuli-responsive microgels, cellular microgelation, pure-cell building blocks, and smart biomanufacturing in next-generation organoid engineering.