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Page 2 of 21 Zhang et al. Soft Sci 2024;4:23 https://dx.doi.org/10.20517/ss.2023.58
INTRODUCTION
Room temperature liquid metals (LMs) typically refer to gallium (Ga) metal and Ga-based low-melting
[1]
point alloys . LMs are now extensively used in biomedical applications owing to their excellent electrical,
thermal, mechanical, and biological properties . In the case of conventional biomaterials, such as rigid
[2-4]
metals, ceramics, and silicon and their complexes, it is difficult to match their elastic moduli with those of
[5]
human body tissues . Unlike this, LMs appear in fluid at room temperature and can, thus, easily be
incorporated into various soft materials or even directly printed on the biological skin to work as the
electronic tattoo (E-tattoo), which allows the quick fabrication of various bioelectronic devices . In recent
[6]
years, fundamental discoveries and technological advances in this field have led to the establishment of
novel therapeutic and diagnostic approaches, including the cutting-edge area of neural interfaces [7-10] .
Particularly, introduction of the LM as a connecting or functional recovery channel for the transected sciatic
nerve significantly innovated the classical category of neurorepairing and interface reconstruction.
[10]
The neuro-electrical interface (NEI) serves as a bidirectional communication bridge between the nervous
system and external electronic devices and typically includes the tissue and the sensing interfaces. The tissue
interface converts biological signals from the nervous system into electrical signals (e.g., nerve conduits).
The sensing interface realizes the acquisition and stimulation of signals (e.g., nerve electrodes).
Conventional NEI mostly uses rigid materials. At present, NEI is developing in the direction of full
flexibility, miniaturization, and high integration. One of the key roles of NEI is to transmit electrical signals
quickly, efficiently and accurately. Therefore, it is extremely valuable to improve the conductivity of the
electrodes and reduce the interfacial impedance between the electrodes and the neural tissue. The
6
conductivity of Ga-based alloy is 3.4 × 10 S/m, which is in the same order of magnitude as that of platinum
6
(Pt, 9.5 × 10 S/m), and it can be further enhanced by mixing a certain percentage of metal powders with
high conductivity [e.g., silver (Ag) and copper] [11-15] . In addition, micrometer-scale LM electrodes can be
prepared using various processes, such as printing, injection, selective wetting, and deposition. Ga-based
LM also possesses biocompatibility and has been applied to prepare epidermal electrodes and in vivo
implantable electrodes. Therefore, considering the mechanical and electrical properties, preparation
method, and biocompatibility, Ga-based LM is a suitable candidate for preparing flexible stretchable nerve
electrodes.
The nervous system is classified into the central (CNS) and peripheral nervous systems (PNS). The CNS
includes the brain and the spinal cord; in this case, the core hardware of the NEI is the electrodes used for
recordings and stimulations [Figure 1A]. In the PNS case, the core hardware of the NEI consists of nerve
electrodes and nerve conduits used to connect and repair nerves [Figure 1B]. Note that the nerve electrodes
for CNS and PNS tend to differ in structures. The output of the nerve electrode is the external signal
processor, while the nerve conduit acts on the autologous nerve. Thus, nerve electrodes used to be made as
sheet-like arrays of electrodes that fit very snugly into the tissues. The nerve conduit tends to be a cylindrical
conductor of electricity, similar to the morphology of the nerve.
Optimization strategies for nerve electrodes and nerve catheters are closely related to the development of
electrode and catheter materials. The review of the development of electrode materials can be dated back as
early as 1981. Hamill et al. adopted flint or borosilicate glass and metal wire to prepare the diaphragmic
clamp . Subsequently, the neuro-electrodes composed of gold (Au), Pt, Ag, stainless steel, tungsten (W),
[16]
doped polysilicon and other metals have been used [17-23] . The schemes listed above have been mainly based
on rigid materials, which may cause damage to soft human tissues. Long-term exposure to foreign bodies
may also lead to progressive inflammatory and fibrotic reactions, further causing neuroglial scarring or loss
of neurons . To enable better interaction between the CNS and external machines, it is becoming
[24]

