Hydrogel microspheres for precision biomedicine: network engineering, microfabrication, and therapeutic applications

Hydrogels and hydrogel microspheres have emerged as highly adaptable biomaterial platforms for precision biomedicine, owing to their hydrated polymer networks, tissue-like physicochemical properties, and capacity to host drugs, biomacromolecules and living cells. In particular, hydrogel microspheres extend the utility of bulk hydrogels by introducing injectability, large interfacial area, modular assembly, tunable microporosity and spatially programmable microenvironments. These features make them attractive for localized drug delivery, cell transplantation, tissue regeneration and emerging therapeutic systems. In this review, we summarize the major physical and chemical strategies used to construct hydrogel networks, and compare representative fabrication methods for hydrogel microspheres, including emulsion polymerization, electrospraying, microfluidics and photolithography. We further discuss how network chemistry, particle geometry, fabrication precision and microsphere assembly influence cargo loading, release behavior, cell compatibility, mechanical performance and in vivo functionality. Representative biomedical applications are then reviewed, with emphasis on sustained drug delivery, cell delivery and tissue engineering, as well as emerging uses in soft tissue reconstruction, neural guidance and compartmentalized bioactive systems. Finally, we highlight key challenges that must be addressed for clinical translation, including scalable manufacturing, batch-to-batch reproducibility, sterilization, biosafety, degradation control and application-specific validation. Overall, this review bridges existing research gaps by elucidating the interplay between network chemistry and particle geometry. Furthermore, it establishes criteria for selecting optimal microfabrication techniques, guiding the evolution of hydrogel microspheres from simple delivery carriers to engineered therapeutic microenvironments through the integrated design of materials and bioengineering.