School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, China.
Analysis and Measurement Center, Tianjin University, Tianjin, 300072, China.
Macromol Rapid Commun. 2024 Oct;45(19):e2400309. doi: 10.1002/marc.202400309. Epub 2024 Jul 16.
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.
冷冻保存是长期储存治疗性蛋白质、红细胞和哺乳动物细胞的常用方法。为了保持这些生物样本的结构完整性和生物活性，必须加入高效的冷冻保护剂。目前，渗透性小分子冷冻保护剂，如甘油和二甲基亚砜，在冷冻储存应用中占主导地位，但它们对细胞和人类健康有害。作为在细胞外空间起作用的膜不可渗透的大分子冷冻保护剂，对冷冻损伤具有显著的膜稳定作用，并且在解冻后很容易去除，具有生物相容性和可行性，是很有前途的候选物。水溶性含羟基聚合物，如聚乙烯醇和多元醇基聚合物，是有效的冰晶再结晶抑制剂，而两性聚电解质、聚两性离子和仿生（糖）多肽可以显著提高解冻后的恢复能力，同时减少膜损伤。在这篇综述中，根据其合成路线、实际用途和冷冻保护机制，系统地总结了合成大分子冷冻保护剂。它为开发高效、安全的细胞冷冻保存提供了具有有效冰晶再结晶抑制活性的高效大分子冷冻保护剂提供了有价值的见解。
