Antifreezing hydrogels for biomedical applications from design strategies to emerging multifunctionality

Antifreezing hydrogels are gaining increasing attention as promising materials for biomedical applications in subzero environments, including cryopreservation, cold-adaptive bioelectronics, wearable sensing, and tissue engineering. Despite recent progress, this is still a relatively underexplored research area, with many fundamental and translational challenges remaining. However, the unique ability of antifreezing hydrogels to sustain flexibility, conductivity, and biological compatibility under freezing conditions underscores their immense potential for future biomedical and engineering innovations. This review provides a targeted overview of the design principles, antifreezing mechanisms, and application-specific adaptations of antifreezing hydrogels. We begin by summarizing fundamental antifreezing strategies, including the incorporation of cryoprotective agents, polymer network engineering, crosslinking architectures, and supramolecular self-healing designs. Particular emphasis is placed on recent advances in hydrogels with integrated strain-sensing, temperature-responsiveness, and multifunctional biosensing capabilities under extreme cold conditions. We then examine cryopreservation-oriented hydrogels, highlighting their ability to suppress ice nucleation, minimize intracellular ice formation, and preserve biological function. The review also explores hydrogel-based cold-adaptive bioelectronics, including low-temperature wearable sensors, flexible circuits, and self-powered interfaces. Finally, we discuss key considerations for clinical translation, such as biocompatibility, degradability, and long-term stability. By linking molecular design to macroscopic performance, this review aims to establish a forward-looking framework for antifreezing hydrogel development across biomedical, environmental, and soft robotic domains. • First mechanisms-to-design roadmap linking freezing physics to hydrogel design strategies for subzero performance. • Strongly bound water as a unifying principle explaining how hydration suppresses ice while preserving mechanics. • Links diverse applications to coupled endpoints (healing, sensing, viability) beyond isolated freezing metrics. • Future-facing directions including bioactives, hybrid networks, data-driven design for subzero-capable biomaterials.