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, 13 (11), e0206137

Biomimetic Extracellular Matrix Coatings Improve the Chronic Biocompatibility of Microfabricated Subdural Microelectrode Arrays


Biomimetic Extracellular Matrix Coatings Improve the Chronic Biocompatibility of Microfabricated Subdural Microelectrode Arrays

Flavia Vitale et al. PLoS One.


Intracranial electrodes are a vital component of implantable neurodevices, both for acute diagnostics and chronic treatment with open and closed-loop neuromodulation. Their performance is hampered by acute implantation trauma and chronic inflammation in response to implanted materials and mechanical mismatch between stiff synthetic electrodes and pulsating, natural soft host neural tissue. Flexible electronics based on thin polymer films patterned with microscale conductive features can help alleviate the mechanically induced trauma; however, this strategy alone does not mitigate inflammation at the device-tissue interface. In this study, we propose a biomimetic approach that integrates microscale extracellular matrix (ECM) coatings on microfabricated flexible subdural microelectrodes. Taking advantage of a high-throughput process employing micro-transfer molding and excimer laser micromachining, we fabricate multi-channel subdural microelectrodes primarily composed of ECM protein material and demonstrate that the electrochemical and mechanical properties match those of standard, uncoated controls. In vivo ECoG recordings in rodent brain confirm that the ECM microelectrode coatings and the protein interface do not alter signal fidelity. Astrogliotic, foreign body reaction to ECM coated devices is reduced, compared to uncoated controls, at 7 and 30 days, after subdural implantation in rat somatosensory cortex. We propose microfabricated, flexible, biomimetic electrodes as a new strategy to reduce inflammation at the device-tissue interface and improve the long-term stability of implantable subdural electrodes.

Conflict of interest statement

The authors have declared that no competing interests exist.


Fig 1
Fig 1. Fabrication of ECM-coated electrode arrays.
(A) Schematics of the fabrication process of the Au-parylene microECoG arrays (step 1), followed by micro-transfer molding to form the ECM film and UV excimer laser ablation. (B) 3D schematics and dimensions of the ECM-coated arrays (thicknesses not drawn to scale). (C) Representative electrode array coated with a collagen film (dashed area) and assembled with the ACF connector (arrowhead). (D) False colored SEM image of the cross-section of the Au-parylene array coated with the ECM film, post UV excimer laser ablation. (E) Thickness profile of the ECM-coated arrays.
Fig 2
Fig 2. Impedance characterization.
(A) Impedance modulus at 1 kHz of the uncoated, collagen collagen-fibronectin coated arrays. (B-D) Magnitude and phase spectra of the impedance measured in vitro of the Au-parylene electrode arrays (B) uncoated or coated with 20 μm film of (C) collagen, (D) collagen-fibronectin (n = 8). Overlaid lines are the impedance modulus and phase calculated from fitting the experimental data with equivalent circuit models in (E) and (F). (E, F) Equivalent circuit of the electrode/electrolyte interface of the (E) uncoated Au-parylene and (F) ECM coated arrays.
Fig 3
Fig 3. In vivo acute recordings of cortical potentials.
(A) Photograph of the electrode array placed on the surface of the rat barrel cortex. (B) Representative 2 s segments of data recorded from the gold (blue trace), collagen-coated (orange trace), and collagen-fibronectin-coated (green trace) electrodes. Note the large amplitude, ~1-Hz oscillations and smaller, faster rhythms occurring near the peak of each cycle (arrows). (C) Average power spectral density calculated over a 1 min time window for the three electrode types. D, Average cycle-triggered wavelet scalograms for the three electrode types. The color indicates power relative to the phase of the 1-Hz cycle (average cycle shown in black). The number of cycles used to generate the averages is indicated. Power in two frequency ranges, αβ = 5–30 Hz and γ = 50–300 Hz, was coupled to two distinct phases, upslope and peak, of the 1-Hz cycle.
Fig 4
Fig 4. Comparison of Glial Reactivity in Cortex Below Electrode Arrays with and without ECM Coatings.
(A) Cortical sections labeled for microglia/macrophages (Iba1, top rows) or astrocytes (GFAP, middle rows) at 7 or 30 days post-implantation. Bottom rows are the overlay of the sections. (B) Mean cortical reactivity from ECM coated arrays (normalized to the contralateral region). Dashed lines represent the reactivity generated from uncoated array implantation. Data is presented as the mean ± standard error of the mean, n = 4 for each electrode type at each time point. * denotes p<0.05, ** denotes p<0.01, and *** denotes p<0.001. Scale bar = 500 μm. (C) Mean Iba1+ cell counts were obtained by quantifying positive cells from cortical sections labeled for microglia/macrophages at 7 or 30 days post-implantation. (D) Fewer Iba1 positive cells were found in cortex below electrodes coated in collagen or collagen-fibronectin than the uncoated control electrodes. Data is presented as mean ± standard error of the mean, n = 4 for each electrode type at each time point. Data was compared with one-way ANOVA. * denotes p<0.05. Scale bar = 100 μm.

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