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Page 16 of 21 Zhang et al. Soft Sci 2024;4:23 https://dx.doi.org/10.20517/ss.2023.58

Signal acquisition processing integration
In terms of designing the specialized neural interfacing system and integrating the LM electrodes with the
system, there is a need to develop a small, wireless, specialized neural interfacing circuit system compatible
with the LM-based neural electrodes. The major challenge is transmitting and processing considerable
neural information obtained by the LM electrodes. Conventional methods require a cable-connected
interface to transmit the neural signals to a large neural information processing device at the back end. This
inevitably creates open wounds that increase the risk of infection, while the requirement for large
equipment restricts the range of applications for neural interfacing. The key to solving this problem lies in
the miniaturization, wireless connectivity, and implantation of the neural signal transmission and
processing system. A fully implantable and wireless approach not only avoids the presence of open wounds
but also minimizes the risk of infection and neurological damage. Additionally, it allows the animal to move
freely without the constraints of the transmission wires, further enhancing its mobility. The ideal neural
signal transmission and processing system should be able to be implanted in the body as a whole after
encapsulation with LM electrodes, transmit neural signals wirelessly, and provide online processing
capability for these signals. This necessitates using a fully implantable NEI system to address challenges
related to size, biocompatibility, and electrolyte-isolated encapsulation. In addition, the system must be able
to acquire weak neural signals in the presence of the body’s electrophysiological background noise,
overcome the shielding effect of biological tissues, establish wireless communication with electronic devices,
and acquire electrical energy.

Regarding PNI, particularly for large defects, all clinical treatments have drawbacks, and the demand for
improvement never ceases. LMs have shown potential for peripheral nerve connection or repair, attributed
to their achievements in signal recording and stimulation functions.

Electrical connection and electrical stimulation
The most straightforward method for treating PNIs with LMs involves reconnecting nerve pathways. It can
directly reconfigure the basic functions of the pathway through bioelectrical signal connections, preventing
secondary hazards of functional decline, such as atrophy of the target organ of muscle tissue that cannot be
protected by other NGCs. This advantage distinguishes LMs from NGCs, positioning them as highly
appealing innovative materials. Another advantage is that retrograde electrical stimulation from LMs to
proximal neurons may facilitate nerve growth, a technique widely used in specific neuropathy
[104]
treatments . It is the ability of in vivo nerve regeneration that matters in the outcome after graft. And this
electrical stimulation seems to accelerate the progress.

Regenerating bed
As LMs could be manufactured as a film or a conduit, there is no limitation regarding wall permeability and
bioactivity, which could be adjusted using the basal membrane materials. So, the fluid surrounding the
nerve can communicate with the enclosed room by LMs, which let nutrients in and waste metabolites out.
The hollow conduit of LMs connects two stumps of nerve, and offers the space and regeneration beds for
nerve, rather than the barriers, which may be encountered in other metal materials.

Easy application
The film form of LMs is flexible, and could be used as a wrapper, assisting in nerve regeneration when
applied on the outer layer of the injured nerve. The mechanical strength of the conduit could be adjusted by
the base and can match that of the native nerve. So, the LM wall could be strong enough to allow for
suturing and prevent collapsing. Also, because of the softness of LMs, these two forms can be easily
trimmed with microsurgical scissors in clinical applications to accommodate various nerve lengths and
diameters. In addition, LMs have similar modules as nerve tissue and can be tolerant to extensive