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Page 22 of 28 Zhang et al. Soft Sci 2024;4:39 https://dx.doi.org/10.20517/ss.2024.34

with a 95.9% cell survival rate and in-vivo with no inflammation or fibrosis. In detail, Figure 12G shows a
schematic diagram of a brain interface based on ICH. Figure 12H depicts the ICH-based brain interface
composed of ICH and a poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) substrate in an
MRI imaging setting. No artifact on MRI was observed because both ICH and PVDF-HFP are compatible
with MRI. Figure 12I demonstrates the conformal and soft neural electrodes with a 4-channel ICH electrode
for ECoG recording in a rodent model and clear visual-evoked potential signals from the visual cortex was
observed. Therefore, due to the brain-like soft modulus and excellent ionic conductivity, the MRI-
compatible ICH neural electrodes enable the stable monitoring of ECoG, even in the setting of response to
visual stimuli. The ICH-based brain interface can be further extended to record neural responses from
various sensory modalities, such as olfaction, touch, and hearing.

Multimodal implantable hydrogel interfaces represent a significant advancement in neural signal recording,
particularly in overcoming the limitations of traditional metal electrodes, which can compromise
biocompatibility and hinder integration with imaging, CT and MRI. Innovations such as HENIs offer
remarkable transparency, flexibility, and compatibility with MRI and optical imaging techniques. These
features provide a solution for simultaneous recording of spatio-temporal signals. Moreover, the
development of self-expanding and biodegradable electrodes demonstrates a commitment to minimizing
invasiveness, which facilitates a more comprehensive understanding of brain function by enabling the
exploration of various sensory modalities while maintaining stable signal acquisition over extended periods.
Overall, these multimodal interfaces are poised to transform neurotechnological research and therapeutic
applications, which offers new insight into complex neural dynamics and interactions.

CONCLUSION AND OUTLOOK
In conclusion, the long-term monitoring of EEG, ECoG, and LFP or single-neuron activity holds immense
significance for the study of brain science, artificial intelligence, and the diagnosis and treatment of brain-
related disorders. The exploration of both non-invasive and invasive brain interfaces with diverse materials
has been proposed. Among the materials, hydrogels have emerged as a promising interface material for
neural electrodes due to their mechanical combability with biological tissues, exceptional biocompatibility,
and high conductivity. It is expected that this review paper will serve as a valuable source of knowledge and
provide researchers with a reference for the studies and developments in the field of brain signal
monitoring.

Although hydrogel-based interfaces have emerged as a promising solution for the brain signal interfaces
with superior performance, particularly in terms of biocompatibility, long-term stability and multi-channel
monitoring, some key challenges remain for further exploration.

Biocompatibility
Although the high water content and adaptability of hydrogels enhance tissue compatibility after
implantation, their biocompatibility can be limited by the synthesis methods and material components
used, particularly due to potential toxicity or inflammation associated with cross-linking agents and surface
chemistry, which may compromise long-term stability. Possible solutions include employing physical cross-
linking techniques such as freeze-drying and thermal gelation, which allow for the formation of hydrogels
through temperature and pH adjustments without the use of chemical cross-linkers, thus minimizing
sources of toxicity. Additionally, utilizing naturally biocompatible cross-linkers such as alginate or chitosan
can create a non-toxic environment suitable for long-term neural implantation. Moreover, incorporating
anti-inflammatory molecules on the hydrogel surface, with controlled release during the initial implantation
phase, may help mitigate early-stage immune responses.