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Page 4 of 21 Zhang et al. Soft Sci 2024;4:23 https://dx.doi.org/10.20517/ss.2023.58

[25]
minimal damage to neural tissue . Among the many developments of flexible neural interfaces, LMs have
gained attention in recent years. As a class of materials with ease of preparation, they have been extensively
tried in the fields of drug delivery, cancer therapy, and medical devices [26-28] . Their high ductility, good
biocompatibility, and excellent electrical conductivity make them outstanding candidates for fabricating
flexible neural interfaces. A review of the development of neuro electrodes [Figure 1C] indicates that their
transformation from rigid to flexible forms is a logical trend [7,29-32] . While flexible electrodes develop to an
end-point liquid form, which can be well adapted to the human body and applied in it.

In addition to their use for the preparation of nerve electrodes, LMs can also be adopted for preparing nerve
conduits. Nerve conduits are used to connect and repair peripheral nerves. Peripheral nerve injury (PNI) is
[33]
the most common cause of disability in the world . The medical target is to restore critical function and
sensibility to the extremity by repairing the nerve directly under no-tension conditions while anticipating
innate nerve regeneration [34,35] . Autografting of the nerve defect is currently considered the gold standard
procedure [35,36] but causes donor site morbidity . Alternatives, such as commercial allograft nerves and
[37]
nerve guidance conduits (NGCs), are available [38,39] , with allografts providing a scaffold for nerve
regeneration. However, NGCs have limitations primarily in their ability to regenerate nerve function and
prevent undesirable outcomes such as slow axonal growth or misdirection at the site of injury, atrophy of
the target organ, and failure of re-innervation [40,41] . Therefore, they currently only show acceptable outcomes
for short, sensory nerve gaps [42,43] . The ideal NGC could stimulate proximal nerve growth and allow
bioelectricity to be conducted to emulate the natural environment in its distal part. There are four main
categories of conductive materials currently used for nerve bridging: hydrogels, polymers, carbons, and
metals [Figure 1D], in which the metals have the highest conductivity rate [8,44-47] that may theoretically
achieve instant bioelectricity. LMs are one of these materials that stand out for their modulus (similar to
that of nerve tissue) and excellent flexibility [7,10] . Their great potential as bridging materials provides an
alternative for conventional NGCs in treating large nerve gaps.

This review first introduces the composition, classification, and development trend of NEI technology and
summarizes how conductive LM materials can be utilized to realize the fabrication of flexible neuro-
electrodes and stretchable nerve conduits. Subsequently, the electrical, mechanical, biological, and fluidic
properties of LMs are systematically presented. These properties enable LMs to be fabricated into NEI using
various preparation processes, including printing, injection, microfluidics, and deposition. Finally, this
study summarizes the research progress and applications of LM-based NEI and provides an outlook on its
future challenges.

LMS: BASIC PROPERTIES
The low-melting-point metal monomers in a liquid state near room temperature are mercury (Hg), cesium
(Cs), and Ga. Among these, Hg is toxic, and Cs is too active chemically. Ga is more stable in air and has a
lower melting point and higher boiling point, and has thus been extensively studied and applied. LMs used
in NEI are dominated by Ga-based alloys. The elements of these alloys usually include Ga, lead, tin (Sn),
and indium (In). Different compositions and proportional configurations may lead to varying properties of
the alloys, and some typical properties are listed in Table 1. To explore the application of LMs in neural
interfaces, focus should be placed on relevant properties when they function as tissue interfaces, i.e., in
surface tension and double electro-layer models. Meanwhile, the electrical properties, biocompatibility, and
mechanical properties should be considered when applied to organisms.