1Department of Mechanical Engineering, University of Minnesota, Minneapolis, USA.
Department of Mechanical Engineering; Department of Biomedical Engineering, University of Minnesota, Minneapolis, USA.
Cryo Letters. 2020 Jul-Aug;41(4):185-193.
Cryoprotective agents (CPAs) are routinely applied in cryopreservation protocols to achieve the vitrified state thereby avoiding the damaging effects of ice crystals. Once the CPA has been added, the system needs to cool at a rate ≥ critical cooling rate (CCR) to avoid ice crystallization and successfully enter the vitrified state. Subsequently, upon warming the system needs to meet or exceed a critical warming rate (CWR), often one to two orders of magnitude higher than the CCR, to avoid ice formation and return the system to physiological temperatures for use. Many experimental and theoretical studies have been published on CCRs and CWRs, and correlation for these rates as a function of concentration has been explored for some single component CPAs, but not the CPA cocktails which are commonly used in tissue and organ cryopreservation. In this paper, we summarize the available data of CCRs and CWRs for a variety of CPAs, and suggest a convenient mathematical expression for CCR and CWR that can guide general use for cryoprotective protocol, but also highlights the critical need for further study on CPA cocktails and tissue systems in which CPAs may behave differently and/or may not be fully equilibrated to the loaded CPA.
冷冻保护剂 (CPAs) 通常在冷冻保存方案中应用，以达到玻璃化状态，从而避免冰晶的破坏性影响。一旦添加了 CPA，系统需要以≥临界冷却速率 (CCR) 的速率冷却，以避免冰晶形成并成功进入玻璃化状态。随后，在加热系统时，需要满足或超过临界升温速率 (CWR)，通常比 CCR 高一个到两个数量级，以避免冰晶形成并将系统恢复到生理温度以供使用。已经发表了许多关于 CCR 和 CWR 的实验和理论研究，并探索了一些单一成分 CPA 作为浓度函数的这些速率的相关性，但没有探索常用于组织和器官冷冻保存的 CPA 混合物。在本文中，我们总结了各种 CPA 的 CCR 和 CWR 的可用数据，并提出了一个方便的 CCR 和 CWR 的数学表达式，该表达式可以指导一般的冷冻保护方案使用，但也突出了进一步研究 CPA 混合物和组织系统的迫切需要，在这些系统中，CPA 可能表现不同和/或可能没有完全平衡到加载的 CPA。
