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Innovations in Cryoprotectant Chemistry: Structure–Activity Relationships and Biomedical Applications

Cryopreservation is indispensable for the long-term storage and distribution of cells, tissues, organoids, and other biological products. Its success, however, remains constrained by ice formation, osmotic stress, and damage to cellular membranes and other microstructures during cooling and rewarming. Conventional cryoprotectants, such as dimethyl sulfoxide and glycerol, are widely used but may compromise cell function and require complicated downstream processing due to their cytotoxicity, limiting clinical translation. New opportunities to design safer and more effective cryoprotectants are being created by recent advances in small-molecule chemistry, polymer science, supramolecular chemistry, biomimetic materials, and computational modelling. Rational development of next-generation cryopreservation technologies requires understanding of the influence of molecular structure on ice modulation, permeability, vitrification, and toxicity.This research topic aims to establish a chemistry-centered framework for understanding and optimizing cryoprotectants. Particular emphasis will be placed on structure-activity relationships that connect molecular composition, functional groups, stereochemistry, molecular weight, architecture, and self-assembly behavior with physicochemical and biological performance. We welcome studies that elucidate the molecular mechanisms of cryoprotection, including interactions with water, ice, lipid membranes, proteins, and other cellular components. The collection will highlight emerging approaches such as ice-recrystallization inhibitors, synthetic polymers, peptides, amino acids, sugars, nanomaterials, and multicomponent cryoprotective formulations. By integrating molecular design, experimental characterization, computational prediction, and biological validation, this research topic seeks to accelerate the transition from empirical formulation toward mechanism-guided cryoprotectant discovery and clinically relevant preservation strategies.We welcome Original Research, Review, Mini Review, Perspective, and Methods articles addressing topics including, but not limited to:• Design, synthesis, characterization, and structure–activity relationships of novel cryoprotective molecules and materials;• Physicochemical and molecular mechanisms of cryoprotection, including ice modulation, vitrification, and interactions with biological components;• Evaluation and prediction of cryoprotectant performance through experimental, computational, and data-driven approaches;• Development of biocompatible and multicomponent cryoprotective formulations;• Biomedical applications in the preservation of cells, tissues, organoids, engineered biological products, and organs.Contributions should provide clear chemical or mechanistic insight rather than reporting protocol optimization alone. Topic editors: Xiaojie Sui, Yihang Gao Source: https://www.frontiersin.org/research-topics/87263/innovations-in-cryoprotectant-chemistry-structure-activity-relationships-and-biomedical-applications

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