In vitro biocompatibility evaluation of functional electrically stimulating microelectrodes on primary glia

Christopher T Tsui; Soroush Mirkiani; David A Roszko; Matthew A Churchward; Vivian K Mushahwar; Kathryn G Todd

doi:10.3389/fbioe.2024.1351087

In vitro biocompatibility evaluation of functional electrically stimulating microelectrodes on primary glia

Front Bioeng Biotechnol. 2024 Jan 19:12:1351087. doi: 10.3389/fbioe.2024.1351087. eCollection 2024.

Authors

Christopher T Tsui^{1

2

3

4}, Soroush Mirkiani^{3

4}, David A Roszko^{3

4}, Matthew A Churchward^{2

3

4

5}, Vivian K Mushahwar^{3

4

6}, Kathryn G Todd^{1

2

3

4}

Affiliations

¹ Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada.
² Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
³ Neuroscience and Mental Health Institute (NMHI), University of Alberta, Edmonton, AB, Canada.
⁴ Sensory Motor Adaptive Rehabilitation Technology (SMART) Network, University of Alberta, Edmonton, AB, Canada.
⁵ Department of Biological and Environmental Sciences, Concordia University of Edmonton, Edmonton, AB, Canada.
⁶ Division of Physical Medicine and Rehabilitation, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Abstract

Neural interfacing devices interact with the central nervous system to alleviate functional deficits arising from disease or injury. This often entails the use of invasive microelectrode implants that elicit inflammatory responses from glial cells and leads to loss of device function. Previous work focused on improving implant biocompatibility by modifying electrode composition; here, we investigated the direct effects of electrical stimulation on glial cells at the electrode interface. A high-throughput in vitro system that assesses primary glial cell response to biphasic stimulation waveforms at 0 mA, 0.15 mA, and 1.5 mA was developed and optimized. Primary mixed glial cell cultures were generated from heterozygous CX3CR-1^+/EGFP mice, electrically stimulated for 4 h/day over 3 days using 75 μm platinum-iridium microelectrodes, and biomarker immunofluorescence was measured. Electrodes were then imaged on a scanning electron microscope to assess sustained electrode damage. Fluorescence and electron microscopy analyses suggest varying degrees of localized responses for each biomarker assayed (Hoescht, EGFP, GFAP, and IL-1β), a result that expands on comparable in vivo models. This system allows for the comparison of a breadth of electrical stimulation parameters, and opens another avenue through which neural interfacing device developers can improve biocompatibility and longevity of electrodes in tissue.

Keywords: astrocyte; biocompatibility; electrical stimulation; microelectrode; microglia; neuroinflammation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors are grateful for financial support from Alberta Health Services, the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Foundation for Innovation, the Canadian Institutes of Health Research, the US Department of Defense, the University of Alberta Faculty of Medicine and Dentistry, and the Davey Endowment for Brain Research. VM is a Canada Research Chair in Functional Restoration. NSERC grant number is 06062.