Bioinspired (Glyco)Polypeptides for Ice-Control and Cell Cryopreservation

Cryopreservation is a powerful technology providing fundamental support for basic biomedical research and clinical translation. Currently, cryoprotectants are commonly incorporated during the cryopreservation of cells to preserve their phenotypes and post-thaw functionality. However, existing cryoprotective strategies still face crucial challenges in developing highly efficient and biocompatible approaches for storing various types of cells. Inspired by antifreeze (glycol)proteins, which are endogenous in antifreeze or freeze-tolerant organisms for survival under subzero conditions, (glyco)polypeptides and analogues are developed with ice-controlling properties and cryoprotective effects to maintain cellular viability and function after cryopreservation. The protein-mimetic structures endow (glyco)polypeptides with advantages of biocompatibility, chemical structural diversity, multiscale tunability, and potential for economically large-scale preparation. This review summarizes the synthesis, secondary structures, and self-assembly behaviors of these (glyco)polypeptides, serving as a valuable bridge connecting polymer architectures to their applications as macromolecular cryoprotectants. The roles of (glyco)polypeptides are emphasized, including their activities and underlying protective mechanisms in ice nucleation, ice shaping, and ice recrystallization inhibition, as well as their cryopreservation performance for cells. Finally, in view of the requirement for a precise understanding of structure-property relationships, the prospects of multifunctional (glyco)polypeptides are discussed, with an outlook on the integration of machine learning.