Cryopreservation Techniques for Biological Systems

Cryopreservation encompasses a suite of methods for the long-term storage of biological materials by arresting biochemical activity through low temperatures. Traditional slow-freezing approaches use permeating cryoprotectants such as dimethyl sulfoxide or glycerol to mitigate intracellular ice formation, followed by controlled cooling rates to balance solute effects and ice nucleation. More recent advances have focused on vitrification, in which high concentrations of cryoprotectants and rapid cooling produce an amorphous, glass-like state that eliminates ice crystallisation. Macromolecular cryoprotectants, including synthetic polymers and biomimetic antifreeze agents, are emerging to reduce toxicity and improve post-thaw viability. Parallel efforts address the challenges of heterogeneous systems, from single-cell suspensions and red blood cells to three-dimensional tissue constructs and whole organs. Key damage pathways—ice formation, solution effects and recrystallisation—underpin the design of both chemical and physical strategies, such as ice-binding inhibitors, nanowarming technologies and hypothermic storage media. Taken together, these techniques aim to expand organ banking, enhance cell-based therapies and secure biodiversity resources, while ensuring functional integrity upon warming and integration with host systems.

Research from Nature Portfolio

Recent studies have advanced the chemical toolbox for cryopreservation. A comprehensive review has mapped damage pathways in cellular systems and evaluated small-molecule and macromolecular approaches, including ice binders, ice nucleation inhibitors and bio-inspired polymers, setting a framework for discovery of next-generation cryoprotectants. Building on this, molecular simulations and quantitative experiments have revealed the atomistic origins of ice recrystallisation inhibition by poly(vinyl) alcohol, demonstrating that polymer volume and surface contact area, rather than lattice matching, govern activity. This insight provides concrete guidelines for rational design of synthetic ice-inhibiting agents. In parallel, organ cryopreservation has reached a milestone: vitrified kidneys stored for extended periods have been successfully rewarmed via magnetic nanoparticle-mediated nanowarming, achieving rapid, uniform heating and restoring full renal function after transplantation in a rat model. This work highlights the feasibility of planned organ banking and paves the way for clinical translation.

Cryopreservation Techniques for Biological Systems publication trend

The graph below shows the total number of articles in cryopreservation techniques for biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Cryoprotectant: A substance that protects biological material from freezing damage by reducing ice formation and stabilising cellular structures.

Vitrification: The process of transforming a solution into an amorphous, glass-like state by rapid cooling and high solute concentrations to prevent ice crystallisation.

Nanowarming: Uniform and rapid rewarming of vitrified tissues or organs via activation of magnetic nanoparticles distributed through the vasculature.

Ice recrystallisation inhibition (IRI): The prevention of ice crystal growth and reshaping during warming or temperature fluctuations, critical for maintaining cell viability.

Hypothermic storage: Preservation of biological constructs at mild subzero or near-zero temperatures in specialised solutions, avoiding full cryogenic freezing.

References

1. Chemical approaches to cryopreservation. Nature Reviews Chemistry (2022).
2. The atomistic details of the ice recrystallisation inhibition activity of PVA. Nature Communications (2021).
3. Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nature Communications (2023).
4. Core–Shell Microfiber Encapsulation Enables Glycerol-Free Cryopreservation of RBCs with High Hematocrit. Nano-Micro Letters (2023).
5. Prevascularized spongy-like hydrogels maintain their angiogenic potential after prolonged hypothermic storage. Bioactive Materials (2024).