Xu X, Cui Z F
Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UK.
Biotechnol Prog. 2003 May-Jun;19(3):972-81. doi: 10.1021/bp025674n.
Cryopreservation is likely the choice for long-term preservation of natural and engineered tissues, and high concentration multiple cryoprotective agents (CPAs) are usually used in such a process. To achieve high cell viability after cryopreservation, cells at all locations within the tissue must be protected properly by the CPAs during freezing. It is hence essential to know the distribution and concentration of CPAs within the tissue during multiple-CPA addition, to maximize cell survival and minimize tissue damage. In this work, a model to describe the CPA transport during multiple-CPA addition in a one-dimensional porous medium, as a simplified model of living tissue, was developed on the basis of the Maxwell-Stefan (M-S) equations. The UNIFAC and UNIQUAC models were used to evaluate the activity coefficients, and the Siddiqi-Lucas correlation was used for estimation of Maxwell-Stefan diffusivities. Simulations were carried out to examine the effect of temperature, tissue property, CPA type and the interactions between solutes on the CPA transport within construct during the CPA addition. It was found that these parameters, especially the interactions between the different CPA molecules, which was neglected before, significantly affect the transport of each individual CPA component. It is hence concluded that the traditional single-component analysis on the CPA diffusion is not adequate to quantify the multiple-CPA distribution in the tissue, particularly when the CPA concentrations are relatively high.
低温保存可能是天然组织和工程组织长期保存的选择，在这个过程中通常会使用高浓度的多种冷冻保护剂（CPA）。为了在低温保存后获得高细胞活力，在冷冻过程中组织内所有位置的细胞都必须受到CPA的妥善保护。因此，了解在添加多种CPA期间组织内CPA的分布和浓度至关重要，以便最大限度地提高细胞存活率并最小化组织损伤。在这项工作中，基于麦克斯韦-斯蒂芬（M-S）方程，开发了一个模型来描述在一维多孔介质（作为活组织的简化模型）中添加多种CPA期间的CPA传输。使用UNIFAC和UNIQUAC模型评估活度系数，并使用Siddiqi-Lucas关联式估算麦克斯韦-斯蒂芬扩散系数。进行了模拟，以研究温度、组织特性、CPA类型以及溶质之间的相互作用对添加CPA期间构建体内CPA传输的影响。研究发现，这些参数，尤其是之前被忽略的不同CPA分子之间的相互作用，会显著影响每个CPA组分的传输。因此得出结论，传统的关于CPA扩散的单组分分析不足以量化组织中多种CPA的分布，特别是当CPA浓度相对较高时。
