Influence of Biphasic Stimulation on Olfactory Ensheathing Cells for Neuroprosthetic Devices

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

Olfactory Ensheathing Cells for Tissue Engineering the Neural Interface

Mechanical disparities between conventional platinum (Pt) electrodes and neural tissue often result in scar tissue encapsulation of implantable neural recording and stimulating devices. To overcome this issue tissue engineered living-electrode surfaces seeded with olfactory ensheathing cells (OECs) have been proposed. OECs are supportive glial cells in the olfactory nervous system which can transition through glial scar tissue while supporting the outgrowth of neural processes. To determine the feasibility of utilising OECs with neural cells at the electrode interface, the influences of novel polymeric electrode materials and clinically relevant levels of electrical stimulation (ES) on OECs must first be determined. Conductive hydrogel (CH) electrode coatings are presently being explored as substrates in the living-electrode system. To determine an ideal CH to support OECs, eight CH variants were explored in comparison to conventional Pt electrodes. CH variants were based on biosynthetic hydrogels, consisting of poly(vinyl alcohol) (PVA) and heparin, through which the conductive polymer (CP) poly(3,4-ethylenedioxythiophene) (PEDOT) was electropolymerised. The biochemical composition was varied through incorporation of the biomolecules gelatin and sericin in combinations of 1-3 wt %. Cyclic voltammetry and electrochemical impedance spectroscopy demonstrated that adding these biological molecules had minimal effect on the ability of the coating to safely transfer charge. However, the incorporation of 1 wt % gelatin in the hydrogel was sufficient to significantly increase the attachment and proliferation of OECs compared to the non-functionalised CH. OECs cultured on Pt and CH surfaces containing 1 wt % gelatin 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. To determine the functionality of OECs following stimulation the production of the secreted nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and the neurite outgrowth inhibitor-A (NOGO-A)) were assessed by an enzyme-linked immunosorbent assay (ELISA). Concentrations of these proteins in the media were too low to be detected by either direct or sandwich ELISA methods. However, OECs co-cultured with PC12 cells were found to support neural cell differentiation (an indirect measure of neurotrophic factor production) following ES

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes

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

Nerve block waveforms require the passage of large amounts of electrical energy at the neural interface for extended periods of time. It is desirable that such waveforms be applied chronically, consistent with the treatment of protracted immune conditions, however current metal electrode technologies are limited in their capacity to safely deliver ongoing stable blocking waveforms. Conductive hydrogel (CH) electrode coatings have been shown to improve the performance of conventional bionic devices, which use considerably lower amounts of energy than conventional metal electrodes to replace or augment sensory neuron function. In this study the application of CH materials was explored, using both a commercially available platinum iridium (PtIr) cuff electrode array and a novel low-cost stainless steel (SS) electrode array. The CH was able to significantly increase the electrochemical performance of both array types. The SS electrode coated with the CH was shown to be stable under continuous delivery of 2 mA square pulse waveforms at 40,000 Hz for 42 days. CH coatings have been shown as a beneficial electrode material compatible with long-term delivery of high current, high energy waveforms