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Page 20 of 28 Zhang et al. Soft Sci 2024;4:39 https://dx.doi.org/10.20517/ss.2024.34

Figure 11. Implantable hydrogel interfaces. (A and B) Development of optically controlled “living electrodes” with long-projecting axon
tracts for a synaptic brain-machine interface [99] ; (C and D) Adaptive and multifunctional hydrogel hybrid probes for long-term sensing
and modulation of neural activity [100] ; (E-F) Electrodes with robust conducting hydrogel coating for neural recording and modulation [101] .

Multimodal implantable hydrogel interfaces
As mentioned above, ECoG and LFP electrodes are essential neural signal recording and widely used in
various applications, especially for neuroscientific research. However, ECoG electrodes that use metal as a
conducting material exhibit poor biocompatibility and can easily damage the brain tissue. In addition, the
low transparency and incompatibility with magnetic field of the metal also limits their multimodal
applications, such as the cooperation with optogenetics, two-photon, and MRI, which is of great
significance in neuroscientific research.

To overcome the challenges, Prof. Zhang from the Changchun Institute of Applied Chemistry developed a
hydrogel-elastomer neural interface (HENI) with PVA-artificial cerebrospinal fluid (ACSF) as the
conductive layer and polydimethylsiloxane (PDMS) as the insulator . It can be used as a subdural cortical
[102]
electrode as illustrated in Figure 12A and B. In contrast to traditional metal electrodes, HENI electrodes
offer remarkable biocompatibility and compatibility with MRI. It shows a potential to be integrated with
optical imaging techniques due to the high transparency. The high translucency of the PVA-ACSF hydrogel
allows the simultaneous acquisition of neuronal calcium signals and vascular signals beneath the electrode
using two-photon microscopy. As a result, high-quality cortical neural signals with excellent spatiotemporal
resolution can be recorded. This multimodal approach enables researchers to observe and analyze neuronal
activity and dynamic vascular changes under various physiological or pathological conditions, which can
provide novel insights and methods for the study of brain region interactions and neurovascular
mechanisms.

Driven by the demands of multimodal implantable brain electrodes, our research team also developed a
multimodal transparent conductive hydrogel electrode. The electrode is designed and fabricated with a
polymer network comprising polyvinyl alcohol, hexadecyltrimethylammonium chloride, and hyaluronic
[85]
acid (PVA@HACC@HA) through a freeze-thaw method as illustrated in Figure 12C-F . No toxic or
harmful cross-linking agents and initiators were used during the synthesis of the hydrogel to ensure