Microfluidic engineering of microgels: fabrication methods, structural design, assembly strategies, and biomedical...

Microgels, valued for their superior hydrogel properties and large specific surface area, serve as microcarriers for drugs or cells in tissue engineering, demonstrating vast potential in biomedicine. Microfluidic technology currently enables the efficient, precise, and controllable fabrication of microgels within microscale channels. However, achieving precise fabrication demands specialized expertise in optimizing raw materials, crosslinking strategies, and reaction conditions within these channels, posing a significant challenge for researchers and clinicians lacking specialized training. Consequently, a comprehensive and systematic review is urgently needed to provide a detailed guide for those entering the field. This article reviews development strategies for microgels on microfluidic platforms and their recent advances in biomedical applications. First, it outlines fundamental techniques for microfluidic microgel fabrication, including crosslinking method selection and structural design principles for microgel synthesis within microchannels. Furthermore, we delve into the assembly mechanisms and functional properties of microgels in biomedical contexts, establishing key theoretical frameworks for constructing complex biomimetic tissue structures and achieving customizable functions. Simultaneously, the review extensively explores cutting-edge applications of microgels across various interdisciplinary biomedical fields, such as cell sorting, 3D cell culture, cell therapy, organoid models, 3D bioprinting, tissue regeneration, and controlled drug release. These case studies demonstrate the versatility of microfluidic-derived microgels in meeting biomedical and preclinical research needs while inspiring interdisciplinary connections. Finally, challenges facing microgels in biological applications are discussed, alongside insights into future research directions. STATEMENT OF SIGNIFICANCE: Microgels offer revolutionary potential in biomedicine but are hard to make reliably using standard methods. Microfluidics enables precise microgel creation, yet its complexity limits wider use. This review represents the most exhaustive and up-to-date synthesis of microgel fabrication strategies and their biomedical applications. It uniquely bridges fundamental fabrication techniques, structural design, assembly strategies, functional properties, and practical implementation, empowering scientists and clinicians without specialized expertise. Its significance lies in accelerating the field by providing a practical roadmap to overcome technical hurdles, inspiring new research connections, and ultimately speeding up the development of microgel-based therapies for patients. This empowers broader adoption and clinical translation.