Protein and Peptide-Based Strategies for Advanced Cryopreservation.

Cryopreservation effectively halts biological metabolism, placing living specimens in a state of 'suspended animation' for future revival. As a foundational technology for cell-based biomedicine, cryopreservation relies on cryoprotectants (CPAs) to mitigate freezing-induced damage, such as ice formation, protein denaturation, and oxidative stress. However, conventional CPAs like dimethyl sulfoxide and glycerol face practical limitations, including cytotoxicity and cumbersome removal processes, driving the need for novel alternatives. In nature, psychrophilic organisms produce stress-tolerant proteins, such as antifreeze proteins and late embryogenesis abundant proteins, thus enabling themselves to survive in subzero conditions by controlling ice growth, stabilizing membranes, and performing other protective functions. Inspired by these natural systems, this review aims to explore the potential of protein and peptide-based materials as next-generation CPAs. We systematically summarize the characteristics, mechanisms, and cryopreservation applications of natural stress-resistant proteins and their synthetic mimics. Moreover, we discuss key challenges including immunogenicity, scalability, and the rational design of these synthetic mimics, and outline future directions for the development of these biomimetic cryoprotective materials.