Microfluidics-based hydrogel microspheres: Complex structure design and multidisciplinary applications

Hydrogel microspheres have emerged as multifunctional three-dimensional biomaterial platforms, garnering significant research attention in biomedical and analytical fields. Their applications now extend to cutting-edge domains including controlled drug delivery, regenerative medicine, and biosensing technologies. Conventional fabrication methods such as emulsion techniques, three-dimension (3D) printing, and spray drying face inherent limitations in producing structurally sophisticated microspheres, particularly regarding inadequate product uniformity, high production costs, and scalability challenges. The breakthrough development of microfluidic technology has revolutionized the controllable fabrication of hydrogel microspheres, establishing itself as the most promising technology in this field. This review systematically summarizes recent advancements in microfluidics-based hydrogel microsphere preparation technologies, with particular emphasis on innovative strategies for constructing complex architectures and methodological breakthroughs. This review highlights, as a key insight, the unique capability of microfluidics to engineer architecturally sophisticated microspheres and their role in fostering convergence across disciplines like biomedicine and materials science. By critically synthesizing these advances, this work provides a foundational guide for future research, outlining clear pathways for overcoming current scalability and biocompatibility challenges to advance the development of personalized and smart functional microspheres.