A three-dimensional lattice-free agent-based model of intracellular ice formation and propagation and intercellular mechanics in liver tissues.

A successful cryopreservation of tissues and organs is crucial for medical procedures and drug development acceleration. However, there are only a few instances of successful tissue cryopreservation. One of the main obstacles to successful cryopreservation is intracellular ice damage. Understanding how ice spreads can accelerate protocol development and enable model-based decision-making. Previous models of intracellular ice formation in individual cells have been extended to one-cell-wide arrays to establish the theory of intercellular ice propagation in tissues. The current lattice-based ice propagation models do not account for intercellular forces resulting from cell solidification, which could lead to mechanical disruption of tissue structures during freezing. Moreover, these models have not been expanded to include more realistic tissue architectures. In this article, we discuss the development and validation of a stochastic model for the formation and propagation of ice in small tissues using lattice-free agent-based model. We have improved the existing model by incorporating the mechanical effects of water crystallization within cells. Using information from previous research, we have also created a new model that accounts for ice growth in tissue slabs, spheroids and hepatocyte discs. Our model demonstrates that individual cell freezing can have mechanical consequences and is consistent with earlier findings.