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Page 2 of 26 Yang et al. Soft Sci 2024;4:9 https://dx.doi.org/10.20517/ss.2023.43

INTRODUCTION
The field of cryobiology has made significant progress and has drawn increasing attention in the past
decades since technologies derived from this category are closely related to the welfare of humankind,
notably in areas such as organ transplantation, assisted reproduction, and tumor therapy. Despite
encountering significant challenges throughout its development, the field has witnessed remarkable
progress in recent years, largely attributed to the rapid advancements of materials science, which enable
many exhilarating breakthroughs in cryobiology.

Cryosurgery is a medical technique that employs freezing to selectively eliminate undesired tissues (e.g.,
adipose, naevus, tumors, etc.) while minimizing cryogenic injuries to surrounding normal tissues. This
technique has been promoted to replace a wide range of traditional therapies in tumor treatment due to its
minor pain, fewer side effects, and minimal invasiveness to patients . However, due to the intrinsic
[1]
complex constructions and anisotropic thermal properties of living tissues, the frozen region is always
unable to be precisely regulated to conform with irregular tumor tissues . In some cases, freezing regions
[2]
did not fully cover the tumor demarcation; thus, the low freezing efficiency failed to thoroughly kill the
[1]
tumor cells. These technical limitations might lead to occasional recurrences afterward ; moreover,
excessive freezing would ineluctably hurt adjacent healthy tissues and cause severe pain and side effects to
patients. These defects were commonly ascribed to the ununiform and inefficient heat transfer within
biological tissues. In order to overcome this, adjuvants were employed to enhance the freezing efficacy and
regulate the freezing zone, thereby ensuring the elimination of tumors while minimizing damage to healthy
tissues . At the same time, these adjuvants could also: (1) Carry and deliver drug molecules to target
[3,4]
tissues as assisted therapy; (2) Enable in vivo imaging for tracing and monitoring the progress of the
therapy . Currently, the well-studied adjuvants primarily consist of natural molecular adjuvants (such as
[5]
antifreeze proteins , tumor necrosis factor alpha , and glycine ) and nanoparticles, for instance,
[6,7]
[8]
[9]
[14]
[13]
MgO [10,11] , Fe O 4 [3,12] , Al , and Au . Among these, nanoparticles are capable of enhancing heat transfer,
3
homogenizing temperature distribution, and, more importantly, regulating ice nucleation. However, rigid
nanoparticles could poorly match soft biological tissues, potentially leading to abnormal cellular
proliferation or cytokine secretion . Thus, there is an urgent need for a soft and conformal material that
[15]
can interact with tissues in a gentler manner and provide thermal enhancement.
Cryopreservation holds an opposite aim to cryosurgery instead of utilizing cryogenic media to cause
damage; it intends to conserve biological structures and is regarded as the most promising approach to
eternal preservation of biological resources since low temperature leads to metabolic inertness. However,
this technique is also confronted with a huge challenge to preserve vulnerable cells or tissues and large-
[16]
volume organs or even living organisms . The conventional slow-freezing method causes inevitable ice
formation in biospecimens and prolonged exposure to toxic cryoprotectants (CPAs), leading to potential
abnormalities in cell phenotypes, attachment, gene expression, and differentiation . Thus, slow-freezing
[17]
methods could hardly be applied to large-volume tissues and organs . The emergence of the vitrification
[16]
technique seems to bring a silver lining. Vitrification aims to deeply cool down biospecimens without any
bulky ice formation during both the cooling and warming processes [16,18,19] . Therefore, vitrification is
considered as a prospective strategy to tackle subsistent challenges and make a breakthrough in the long-
[16]
term preservation of complex tissues and large organs . Vitrification aims to transit the liquid system into
an amorphous glass state instead of a crystalline state, thus avoiding the mechanical destruction of cellular
structures caused by ice formation. The vitrification process can be comprehended as a competition
between system cooling and crystallization. Taking a homogeneous aqueous system as an example, when
the temperature continuously drops below its melting point, the system will be in a supercooled state, and
ice crystallization tends to happen. Yet, crystallization, consisting of ice nucleation and growth, requires a