Imagine a world where a donated kidney doesn’t need to be transplanted within 36 hours. Where a liver can be stored for months rather than days. Where coral reefs and endangered species can be banked against extinction. The global organ shortage, which kills thousands of patients on transplant waiting lists every year, is solved not by finding more donors, but by storing what we already have.
That world depends on a technology called vitrification: turning biological tissue into glass at ultra-low temperatures, preserving it in time without damaging ice crystals that form inside. It works beautifully at the microscopic scale, in cells, embryos, and small tissue samples. The problem is scaling it up to something the size of a human kidney.
And the core obstacle? The glass keeps cracking.
A 2025 study published in Scientific Reports by researchers at Texas A&M University has identified a surprising, previously overlooked key to solving this problem: the glass transition temperature.
What Is Vitrification and Why Does It Matter?
When biological tissue is frozen conventionally, water inside and around cells forms ice crystals. Those crystals are mechanically destructive; they puncture cell membranes, disrupt tissue architecture, and ultimately kill the cells. This is why conventional freezing works well for some things (sperm, embryos, blood) but fails catastrophically for complex organs.
Vitrification sidesteps ice formation entirely. Instead of freezing, the tissue is rapidly cooled in a solution of cryoprotectants, specialised chemicals that prevent ice from forming until the entire system becomes an amorphous, glass-like solid. No ice. No crystals. Just a perfectly suspended biological snapshot, stable at liquid nitrogen temperatures (around −196°C).
The milestone moment came in 2023, when researchers achieved the first successful vitrification and transplantation of a mammalian organ, a rat kidney that was subsequently rewarmed and shown to be functional. It was a landmark result. But it was also a proof of concept on a small scale. Translating vitrification to human-sized organs introduces a set of physics problems that don’t exist at the rat scale.
The Cracking Problem
The most dangerous of those problems is thermal stress cracking.
When you plunge a large sample into liquid nitrogen, the outside cools dramatically faster than the inside. Different parts of the material contract at different rates. In a liquid, this doesn’t matter much, the material can flow and accommodate the stress. But a glass can’t flow. It’s rigid and brittle; when the stress exceeds its fracture strength, it cracks.
For a vitrified organ, any cracking is catastrophic. A crack propagating through preserved tissue destroys the structural integrity that enables transplantation. The organ doesn’t just look damaged; it is irreparably damaged.
Researchers have been working on this problem for years, mostly by focusing on the physical process of cooling and warming: optimizing cooling rates, developing electromagnetic rewarming techniques that heat tissue more uniformly, and engineering geometric strategies borrowed from metallurgy. These approaches have helped. But they all treat the cracking problem as a transport problem, something to manage by controlling how heat moves through the sample.
The Texas A&M team asked a different question: what if the chemistry of the preservation solution itself is part of the problem?
The Overlooked Variable: Glass Transition Temperature
Every substance that can form a glass has a characteristic temperature at which it transitions from a viscous supercooled liquid into a rigid, brittle solid. This is the glass transition temperature, abbreviated Tg.
For cryoprotectant solutions that have dominated organ vitrification research for decades, such as those based on compounds like DMSO (dimethyl sulfoxide), the glass transition temperature lies within an extremely narrow range: around −120°C to −130°C. This has always been taken for granted. But the Texas A&M researchers noticed something: no one had actually studied what happens when you use solutions with different glass transition temperatures.
The key insight came from a physics principle established in recent materials science research: glass transition temperature and thermal expansion are inversely related. Materials with higher glass transition temperatures expand and contract less with temperature changes. They are, in a physical sense, more dimensionally stable when cooled.
If this relationship holds for cryoprotectant solutions, as the researchers suspected, then solutions with higher Tg values should experience less thermal expansion and contraction, generate lower internal stresses during cooling, and crack less. This was the hypothesis they set out to test.
The Experiment: Watching Glass Crack in Slow Motion
To test this, the team built a custom imaging platform they call a cryomacroscope. Small samples of four different aqueous solutions — each formulated to vitrify completely without ice formation were sealed in tiny cassettes, plunged into liquid nitrogen, then removed and imaged at high resolution as they warmed at room temperature.
The four solutions spanned more than 50°C in glass transition temperature: DMSO solution at −131°C, glycerol at −102°C, xylitol at −87°C, and sucrose at −82°C. To make sense of the resulting images, which showed complex, irregular crack patterns that were difficult to quantify by eye, the researchers trained a deep learning algorithm to automatically detect and measure the cracked area in each image, achieving over 98% accuracy.
The results were unambiguous. As the glass transition temperature increased, cracking decreased consistently across all trials in a statistically significant pattern. The DMSO solution, with the lowest Tg, showed the most extensive cracking. The sucrose solution, with the highest Tg, showed dramatically less. Visually, the difference was striking: what appeared to be shattered glass in the DMSO samples was almost intact in the sucrose samples under identical experimental conditions.
Why This Happens: The Physics Unpacked
To understand why higher Tg solutions crack less, the researchers ran detailed computer simulations of the thermal and mechanical processes occurring during vitrification. The simulations modelled how stress builds up within the sample as it cools, accounting for heat transfer, fluid flow, and the material’s viscoelastic behaviour during the transition from liquid to glass.
Three interacting effects emerged from the analysis, all rooted in the same underlying physics.
First, solutions with lower glass transition temperatures contract more during cooling, both because the per-degree rate of thermal contraction is higher in lower-Tg materials, and because the material remains liquid (and therefore accumulating contraction strain) over a larger temperature range before solidifying. More contraction means more stress.
Second, lower-Tg solutions experience larger temperature gradients across the sample at the glass transition. These gradients prevent stress from relaxing before the material locks into its rigid glassy state, thereby trapping it.
Third, after solidification, lower-Tg glasses continue to contract more rapidly as cooling progresses toward liquid-nitrogen temperature, adding further stress to an already strained system.
Together, these effects mean that the total stress experienced by a lower-Tg glass can be roughly four times that of a higher-Tg glass cooled under identical conditions, well above the fracture threshold of around 2–3 MPa, at which brittle aqueous glasses begin to crack.
What This Means for the Future of Organ Banking
The implications for cryobiology are substantial. The cryoprotectant solutions currently dominating the field were developed primarily to prevent ice formation and minimize toxicity. Their glass transition temperatures were never a design target; they just happened to fall in the −120°C to −130°C range as a consequence of the chemistry.
This study suggests that solutions in this Tg range may, almost by accident, be among the worst possible choices from a thermal stress standpoint, and that there is significant unexplored chemical space at higher glass transition temperatures that could substantially reduce the risk of cracking.
Importantly, higher glass transition temperatures also offer an additional benefit: they confer greater stability against ice crystallisation during cooling, providing a higher safety margin against the ice formation that vitrification is designed to prevent in the first place.
The researchers are clear that this is a finding that points toward future research rather than a ready-made solution. The toxicity of higher-Tg solutions must be evaluated. Their behaviour at the organ scale must be modelled. The relationship between fracture toughness and glass transition temperature in biological preservation chemistry needs a systematic study.
But for a field that has been circling the same small palette of cryoprotectant chemistries for decades, this work opens a genuinely new direction, one guided by a physical principle that, in hindsight, should have been considered much earlier.
The Bottom Line
Cracking during organ vitrification isn’t just bad luck or a transport engineering problem. It is, at least in part, a chemistry problem, specifically one involving the glass transition temperature of the solutions used.
By showing experimentally and computationally that higher-Tg solutions crack significantly less under identical conditions, this Texas A&M study gives cryobiologists a new target variable for designing the next generation of preservation solutions and brings the vision of long-term, damage-free organ banking one step closer to clinical reality.
References:
Kavian S., Sellers R., Arismendi Sanchez G., Alvarez C., Aguilar G. & Powell-Palm M.J. Higher glass transition temperatures reduce thermal stress cracking in aqueous solutions relevant to cryopreservation. Scientific Reports 15, 27903 (2025). https://doi.org/10.1038/s41598-025-13295-7