Influence of Biphasic Stimulation on Olfactory Ensheathing Cells for Neuroprosthetic Devices

Abstract

The recent success of olfactory ensheathing cell (OEC) assisted regeneration of injured spinal cord has seen a rising interest in the use of these cells in tissue-engineered systems. Previously shown to support neural cell growth through glial scar tissue, OECs have the potential to assist neural network formation in living electrode systems to produce superior neuroprosthetic electrode surfaces. The following study sought to understand the influence of biphasic electrical stimulation (ES), inherent to bionic devices, on cell survival and function, with respect to conventional metallic and developmental conductive hydrogel (CH) coated electrodes. The CH utilized in this study was a biosynthetic hydrogel consisting of methacrylated poly(vinyl-alcohol) (PVA), heparin and gelatin through which poly(3,4-ethylenedioxythiophene) (PEDOT) was electropolymerised. OECs cultured on Pt and CH surfaces were subjected to biphasic ES. Image-based cytometry yielded little significant difference between the viability and cell cycle of OECs cultured on the stimulated and passive samples. The significantly lower voltages measured across the CH electrodes (147 ± 3 mV) compared to the Pt (317 ± 5 mV), had shown to influence a higher percentage of viable cells on CH (91–93%) compared to Pt (78–81%). To determine the functionality of these cells following electrical stimulation, OECs co-cultured with PC12 cells were found to support neural cell differentiation (an indirect measure of neurotrophic factor production) following ES.

The impact of electrical stimulation protocols on neuronal cell survival and proliferation using cell-laden GelMA/graphene oxide hydrogels

“…, living tissue), which can vary from system to system. 45,46,48 However, in this paper and for ease of discussion, the definitions of lower (0.1 to 0.75 mA) and higher currents (1 and 2.5 mA) will be used.…”

“…16 However, there are no standard values regarding the voltage threshold of water electrolysis since these values are influenced by various system components, such as the counterelectrode and working electrode compositions. For example, in the literature, voltage magnitudes of 800 mV 45,46 and 600 mV 16 vs. a reference electrode Ag|AgCl have been reported as the voltage threshold for water electrolysis. Two-electrode setup CV was used here since this is the electrode configuration used for the PC12s ES.…”

“…The definition of a ''clinically'' higher or lower current amplitude is related to different factors such as size and surface morphology of the electrode, location, and arrangement, including the distance of the target area (e.g., living tissue), which can vary from system to system. 45,46,48 However, in this paper and for ease of discussion, the definitions of lower (0.1 to 0.75 mA) and higher currents (1 and 2.5 mA) will be used. The voltages shown in the VTMs (defined as V T in Fig.…”

Conductive Hydrogel Electrodes for Delivery of Long-Term High Frequency Pulses

“…Due to the presence of the hydrogel component, CHs swell in aqueous environments, enabling ingress of ions and forming a three dimensional surface through which charge is transduced. The substantially higher charge transfer area introduced by the CH enables coated electrodes to inject greater amounts of charge at lower voltage than their uncoated metallic counterparts and hence enable devices with low power consumption (Kim et al, 2004 ; Sekine et al, 2010 ; Pan et al, 2012 ; Hassarati et al, 2014 , 2016 ). In prior studies by Hassarati et al ( 2014 ) it was shown that CH coatings on cochlear implants imparted a reduction in potential transient of over 50% and maintained more stable electrical properties over a simulated 2 years of activity (two billion stimuli delivered continuously over 3 months in artificial perilymph).…”

Spinal cord injury: Olfactory ensheathing cell‐based therapeutic strategies

“…These emerging studies are also applicable to OEC transplantation protocols. It has been proven that OECs can support neuronal differentiation and secrete neurotrophic factors under bipolar electrical stimulation of conductive hydrogel electrodes (Hassarati et al., 2016). Michael et al.…”