Page 120 - Read Online

Page 2 of 19 Kim et al. Soft Sci 2023;3:18 https://dx.doi.org/10.20517/ss.2023.08

metal-based devices. Thus, organic conductive materials, such as poly(3,4-ethylenedioxythiophene)-
poly(styrenesulfonate) (PEDOT:PSS), have recently been considered as promising candidates. Nonetheless, their
conformability on curvilinear tissues remains questionable. In this study, we developed an injectable conductive
hydrogel (ICH) composed of tyramine-conjugated hyaluronic acid (HATYR) and PEDOT:PSS for MRI-compatible
brain-interfacing electrodes. Our ICH produced low impedance around 5 kΩ even under 10 Hz, demonstrating high
confidence volumetric capacitance. Due to HATYR’s biocompatibility, histological and cytotoxicity assays showed
almost no inflammation and toxicity, respectively; in addition, ICH was able to degrade into 40% of its original
volume within four weeks in vivo. An electrocorticogram (ECoG) array was also patternable by syringe injections of
ICH on a stretchable and flexible elastomeric substrate layer that conformed to curvy brain tissues and successfully
recorded ECoG signals under light stimulation. Furthermore, MRI imaging of implanted devices did not show any
artifacts, indicating the potential of the MRI-compatible hydrogel electrodes for advanced ECoG arrays. This study
provides a promising solution for MRI-compatible neural electrodes, enabling the advancement of chronic neural
interfacing systems for monitoring neurodegenerative diseases.

Keywords: Injectable conducting hydrogel, hyaluronic acid, PEDOT:PSS, electrode array, electrocorticogram, MRI

INTRODUCTION
The development of flexible and stretchable functional materials has enabled advances in both wearable and
[1,2]
implantable bio-integrated electronic devices , which are capable of either sensing physiological/physical
signals generated from various organs or delivering the electrical/optical stimulations to the desired tissue
[3-8]
location in the human body [9-12] . The inherent advantages of such bidirectional and deformable bioelectronic
devices have gained considerable interest in chronic neural interfacing systems for the precise monitoring of
intractable neurodegenerative diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease,
[13]
and epilepsy . As a representative example, a flexible thin electrode array coated with biodegradable silk
fibroin was conformally mounted onto the brain tissue surface and showed high-performance
[14]
electrocorticogram (ECoG) sensing capability with high areal uniformity . Although the cortex-
conformable interfacing approach has improved our understanding of specific brain activities, to further
enable the search of neuronal circuits in the central nervous system (CNS), the information gathered using
brain-interfacing devices should be coupled with those of magnetic resonance imaging (MRI) . In this
[15]
regard, the current utilization of inorganic bio-inert metallic thin films (e.g., Au and Pt) formed by
harnessing conventional deposition processes remains a practical challenge.

Organic flexible conductive materials, such as poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)
(PEDOT:PSS) [16-24] , carbon nanotubes [25-28] , and graphene [29-31] , have been considered promising candidates
for MRI-compatible neural electrodes because they do not produce MRI artifacts [32,33] . To achieve better
conformability even on the gyri and sulci, a rigid island design strategy employing a strain-dissipative wavy
electrode and the mechanically neutral plane has been widely applied to organic conductive materials
supported on stretchable substrates [34,35] . Although such an approach has shown remarkable potential in
providing a high signal-to-noise ratio (SNR) on a large scale, the areal density remains limited in
compensating for the relatively low spatiotemporal resolution of MRI compared to that of the ECoG device,
owing to the use of serpentine interconnects [36,37] . Therefore, intrinsically stretchable composites fabricated
by the optimal mixing of biocompatible hydrogels with organic conductive fillers have the benefit of
reducing cell-to-cell distance efficiently while effectively matching the stiffness of the brain tissue [38,39] .
However, there remain limitations associated with patterning issues, where the conducting fillers in the
conductive hydrogel composites with photo-crosslinking materials reflect the ultraviolet light used in
conventional photolithography, thereby impeding uniform fabrication [40,41] . As an alternative strategy, a
syringe-injectable patterning method may facilitate the conventional patterning process while maintaining