Thermoplastic hydrogels are emerging as promising materials for biomedical applications in sub-zero environments, including cryopreservation, cold-adaptive bioelectronics, wearable sensing, and tissue engineering, and are receiving increasing attention. Despite recent progress, this research field remains relatively underexplored, and many fundamental and translational challenges remain unresolved. However, the unique ability of thermoplastic hydrogels to maintain flexibility, conductivity, and biocompatibility under freezing conditions highlights their significant potential in future biomedical and engineering innovations. This review provides a targeted overview of the design principles, anti-freezing mechanisms, and application-specific adaptations of thermoplastic hydrogels. We first summarize the basic anti-freezing strategies, including the introduction of cryoprotectants, polymer network engineering, crosslinking structures, and supramolecular self-healing design. Special emphasis is placed on the recent advancements in water gel technologies that integrate strain sensing, temperature response, and multifunctional biological sensing capabilities under extreme low temperatures. Subsequently, we study water gels guided by cryopreservation, emphasizing their ability to inhibit ice nucleus formation, reduce intracellular ice formation, and maintain biological functions. The review also explores cold-adaptive bioelectronics based on hydrogels, 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 combining molecular design with macroscopic performance, this review aims to establish a forward-looking framework for the development of thermoplastic hydrogels in the fields of biomedicine, environment, and soft robotics. This research was published in the journal Bioactive Materials under the title "Antifreezing hydrogels for biomedical applications: from design strategies to emerging multifunctionality".
References: DOI: 10.1016/j.bioactmat.2025.12.053