Development of Macromolecular Cryoprotectants for Cryopreservation of Cells

Abstract Cryopreservation is a common way for long‐term storage of therapeutical proteins, erythrocytes, and mammalian cells. For cryoprotection of these biosamples to keep their structural integrity and biological activities, it is essential to incorporate highly efficient cryoprotectants. Currently, permeable small molecular cryoprotectants such as glycerol and dimethyl sulfoxide dominate in cryostorage applications, but they are harmful to cells and human health. As acting in the extracellular space, membrane‐impermeable macromolecular cryoprotectants, which exert remarkable membrane stabilization against cryo‐injury and are easily removed post‐thaw, are promising candidates with biocompatibility and feasibility. Water‐soluble hydroxyl‐containing polymers such as poly(vinyl alcohol) and polyol‐based polymers are potent ice recrystallization inhibitors, while polyampholytes, polyzwitterions, and bio‐inspired (glyco)polypeptides can significantly increase post‐thaw recovery with reduced membrane damages. In this review, the synthetic macromolecular cryoprotectants are systematically summarized based on their synthesis routes, practical utilities, and cryoprotective mechanisms. It provides a valuable insight in development of highly efficient macromolecular cryoprotectants with valid ice recrystallization inhibition activity for highly efficient and safe cryopreservation of cells.