Nature-Inspired Multidisciplinary Strategies for Tissue and Organ Cryopreservation.

Abstract

Cryopreservation of organs and tissues represents a significant advancement in biomedicine, integrating fields such as cell biology, tissue engineering, and organ transplantation. However, this technique faces substantial challenges, primarily due to ice-related damage and biological stress responses. This review first highlights these critical obstacles and then examines the sophisticated strategies that various organisms have evolved to survive extreme cold. Key mechanisms include complex biological stress responses (involving cold signal perception, metabolic reconfiguration) and physical ice-control strategies, such as deep eutectic solvents (DESs), adsorption-inhibition by ice-binding proteins (IBPs), and the crowding assemblies such as coacervates and hydrogels. Inspired by these biological principles, the review discusses significant advances in cryoprotection technology: 1) Innovative cold-adaptation biology applied to organ preservation; 2) Advanced techniques to develop artificial ice-controlling molecules and materials; 3) Advanced rewarming strategies utilizing nanoparticles. Despite this promising progress, key challenges in translating these laboratory innovations into clinical practice are discussed. Finally, we propose an ideal "cocktail-style" cryoprotectant combining vascular-targeted nanoparticles for ice control, extracellular matrix-stabilizing polymers, cell-specific ice regulators, and metabolic modulators, potentially transforming transplant medicine through global organ banking and advancing regenerative therapies.