Engineering Hollow Hydrogel Architectures toward Cutting-Edge Applications

While three - dimensional (3D) printing enables fabrication of hollow geometries through precise ink deposition, its reliance on photo- or thermal-curing often compromises resolution and biocompatibility. Alternatively, aqueous-phase chemical reactions offer a novel pathway for direct conversion of polymer films into high-resolution hollow structures without requiring external energy inputs or templates, yielding superior mechanical integrity. Despite these advances, the incorporation of living cells during hollow hydrogel formation remains a critical challenge. This review provides a comprehensive analysis of two key fabrication strategies: 1) chemical reaction-driven assembly in aqueous media and 2) 3D printing technologies. The respective design principles are critically evaluated. A systematic comparison reveals distinct advantages—aqueous-phase chemical methods offer enhanced resolution and mechanical strength, whereas 3D printing enables the control of customized geometries. Beyond fabrication, how these hollow hydrogel architectures exhibit transformative applications in drug delivery, tissue engineering, and biosensing are explored. By identifying current limitations and future opportunities, this review outlines a roadmap for the rational design of hollow hydrogels that can bridge the gap between structural engineering and clinical translation.