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Yang et al. Soft Sci 2024;4:9 https://dx.doi.org/10.20517/ss.2023.43 Page 19 of 26

LM-mediated heat transfer enhancement
The efficient preservation of biological samples is an important advance in the history of human medicine.
At present, there are relatively sufficient studies and mature techniques for the preservation of cells and
small-scale tissues. However, for large-scale tissues and organs, there is still an unbridgeable gap regarding
heat transfer between biological samples and temperature-controlling medium in the process of heating and
cooling procedures. It is a practical method to enhance heat exchange through by modifying characteristics,
which has been applied for heat dissipation of electronic devices. The modified interface between
biospecimens and the outer solution will enhance the energy transport process directly. In addition,
researchers have also demonstrated that a variety of metal materials, such as metal foil, foam, and mesh, can
achieve an impressive rapid warming rate of more than 1,000 °C/min due to the remarkable induced eddy
[26]
currents under the radiofrequency field that generate heating through concurrent resistive losses .
For the purpose of conformally enhancing heat transfer and achieving a rapid warming rate, LMs are
superior to any other metals that had been tested in previous work, including copper and aluminum,
because of their excellent intrinsic flexibility and shape adaptability. They can be quickly coated on the
surface of biological samples before cryopreservation, and samples with irregular shapes can also be well
coated without dead spots, which avoids complex metal layer preparation and preservation defects caused
by imperfect metal coverage [Figure 6D].

LM-mediated anti-freezing-induced inflammation
Cryopreservation achieves long-term preservation by lowering the temperature to reduce cell metabolism.
However, low temperature is also a major cause of damage to biological samples, such as organs, when
preserved by hypothermic storage or hypothermic machine perfusion. At the macro level, possible organ
damage includes the destruction of vascular networks and tissue structure, which is closely related to
mechanical damage of ice crystals and thermal stress during cooling and rewarming . At the micro-level,
[108]
the blocked blood flow for organs will trigger ischemic injury in the process of preservation. Long-term
ischemia will lead to hypoxia, metabolic disorders, calcium overload, and a cascade of other problems. In
addition, mitochondria are the main target of hypothermia damage, which causes rapid adenosine
triphosphate (ATP) consumption and enzyme activity decrease; it is reported that around 95% ATP will be
[109]
consumed in the first 4h when stored in 0~4 °C , which is harmful to the ATP-based ion exchange (e.g.,
+
+
Na /K -ATPase) and damage the cytoskeleton and membrane integrity, and then, accumulated metabolic
and ion imbalances will pose a serious threat to cell survival . Low temperature also gives rise to the loss
[110]
of cellular antioxidant capacity. Subsequently, the unbalanced antioxidant defense system induces oxidative
stress in cells, producing large amounts of reactive oxygen species (ROS) and ultimately leading to cell
[111]
necrosis and apoptosis . It is also found that gene transcription and protein synthesis are also affected
by the expressions of apoptosis-sensitive genes, such as Bcl-2/Bax, and the activation of caspase
series proteases with respect to cell apoptosis .
[112]

Meanwhile, the apoptotic and necrotic cells will induce the release of damage-associated molecular patterns
(DAMPs) . As a result of the combined adverse conditions above, organs are prone to suffer
[113]
inflammation during and after preservation. Generally speaking, inflammation is an active protective
response produced by the body in the face of pathogens, tissue damage, and other adverse conditions. A
range of immune cells, including T cells and macrophages, are involved in the inflammatory response and
synthesis and release of cytokines, which mediate a series of processes targeting immune stimulation.
However, prolonged inflammation is extremely unfavorable and can easily lead to tissue dysfunction,
cancer, necrosis, and even death. Ga has shown great potential in immunomodulation to suppress the
3+
3+
reaction of the immune system without evident cytotoxicity. Makkonen et al. proved that Ga can suppress