Yanli Cai, Dong Xu, Zi En Chong, Elaine Shi An Chen, Soo Wah Gan, Alvin Shu Kiat Bok, Wen Feng Lu, Wei Zhai, Ching-Chiuan Yen
Microgels, micrometer-sized hydrogel particles, have emerged as versatile platforms for biomedical applications. Recent advances have driven the development of composite microgels that integrate polymers, nanomaterials, and bioactive agents to achieve precise control over their properties. In this review, we provide a comprehensive overview by establishing a systematic framework that links the structural design to the mechanisms of cell regulation, and ultimately to biomedical applications. We examine how composite microgels regulate cells by their intrinsic material cues, including the mechanical, biochemical, and architectural properties, as well as by dynamic mechanisms, such as on-demand stimuli-responsiveness and autonomous pre-programmed kinetics. We then illustrate how these principles are applied across cancer therapy, tissue engineering, and regenerative medicine. Finally, we discuss key challenges of scalability, biosafety, and clinical integration, and outline future perspectives, such as the role of AI-driven design, in advancing personalized medicine and regenerative therapies. • A trade-off-aware, function-driven framework linking composite microgel design to mechanisms of cell regulation and biomedical applications. • Cell regulation principles spanning intrinsic material cues and dynamic control via on-demand stimuli responsiveness and autonomous pre-programmed kinetics. • Comparative synthesis of design strategies and translation of design principles across cancer therapy, tissue engineering, and regenerative medicine. • Translation roadmap based on critical quality attributes (CQAs), scalability, biosafety/clearance, sterilization and clinical integration, and AI-enabled design.