Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation
Introduction
Chronic neural stimulation is utilized in neural prostheses to modify, restore, or bypass a damaged or diseased portion of the nervous system by sensing or delivering electrical pulses to nearby tissue through neural electrodes. Currently, the most clinically successful applications include deep brain stimulators [1], [2] and cochlear implants [3], [4], [5], used to reduce symptoms of Parkinson’s disease and restore auditory function, respectively. Other medical applications of neural electrodes, such as the treatment of retinitis pigmentosa [6], epilepsy [7], depression [8] and chronic pain [9], have also been reported. With the ever-expanding application of neural electrodes, critical attention must be paid to the safety, function and longevity of these devices, which are ultimately dependent on the stability and biocompatibility of the electrode materials.
Currently, most neural electrodes are made primarily from considerably stable metals, such as platinum, gold, iridium, titanium and stainless steel. As these bare metallic electrodes often suffer from poor performance in long-term stimulation and recording due to poor contact with tissue or scar formation, researchers have developed different surface modification strategies for improving electrode functionality. Applying a thin layer of rough and porous coatings on the neural electrodes can easily increase the effective surface area, improve the efficiency in charge transfer and modulate the electrode biocompatibility. Iridium oxide (IrOx) is the most commonly used coating material for neural electrodes [10], [11], [12], [13], as it possesses many unique properties for neural stimulation. IrOx coated electrodes are non-cytotoxic [11], and they have very low impedance and a high charge injection limit, which allows high levels of charge injection without electrode dissolution or water electrolysis [14]. However, IrOx has poor adhesion to underlying substrates, and it may degrade under chronic aggressive stimulations due to its low structural and chemical stability [15], [16].
Recently, conducting polymers, including polypyrrole, polythiophene, and their derivatives, have emerged as new materials for neural interfacing [17], [18], [19], [20], [21], [22]. Conducting polymers can be electrochemically deposited on neural electrodes with easy control over their thickness, and different bioactive molecules can be incorporated into the polymers to promote neuronal growth and adhesion to the electrode surface [21], [23]. Poly(3,4-ethylenedioxythiophene) (PEDOT) has been considered as the most promising conducting polymer because its ordered and well-defined chemical structure offers outstanding conductivity and stability [24]. It has been reported that the electrical properties of neural electrodes can be significantly improved by surface coating with PEDOT [25], [26]. Despite its advantages and promising outlook, conventional PEDOT has yet to be perfected as a coating material for neural electrodes. Our recent study [25] as well as others’ [27] have revealed the unsatisfactory long-term stability of PEDOT coatings during chronic electrical stimulation. PEDOT coatings may form cracks or delaminate under stimulation, which may lead to further coating detachment, thus debilitating the function of the electrode.
Here, in order to fulfill biocompatibility and stability requirements for PEDOT as a coating material, we adopt carbon nanotubes (CNTs) as the dopant for PEDOT polymerization to electrochemically deposit CNT doped PEDOT (PEDOT/CNT) coatings on neural electrodes. CNTs are known for their extraordinary strength, electrical conductivity and chemical stability, and have broad bio-related applications [28], which recently have extended into the area of neural electrodes [29]. CNTs have been shown to be able to promote neuron differentiation [30], stimulate neurite outgrowth [31], improve neuronal performance [32] and recording [29], boost neuronal electrical signaling [33] and act as a substrate for neuronal growth [34], [35]. In addition, previous reports have shown that CNTs can be incorporated into conducting polymers, such as polypyrrole [22], [36], [37] and PEDOT [38], [39] to form composite materials with enhanced properties, including stability. Therefore, it is expected that the PEDOT/CNT as a coating material may preserve the biocompatibility of PEDOT and CNTs, and exhibit enhanced long-term stability. In this work, PEDOT/CNT films were electrochemically coated on Pt microelectrode arrays, and their morphology and electrochemical properties were characterized. The stability of the coatings under both strong acute stimulation and long-term chronic stimulation were investigated in detail. And finally, the biocompatibility of the PEDOT/CNT coatings was tested.
Section snippets
Materials
Multi-walled CNTs with the length of 10–30 μm and diameter of 20–30 nm were purchased from Cheap Tubes Inc. (Brattleboro, USA). 3,4-Ethylenedioxythiophene, glutaraldehyde (25% in H2O), osmium tetroxide (OsO4, 4 wt.% in H2O) and hexamethyldisilazane (HMDS) were purchased from Sigma–Aldrich. Phosphate buffered saline (PBS, pH 7.4, 10 mm sodium phosphate and 0.9% NaCl) was purchased from Sigma–Aldrich. All other chemicals were of analytical grade, and Milli-Q water from a Millipore Q water
Electrodeposition of PEDOT/CNT
The acid-pretreated CNTs are negatively charged in neutral aqueous solution because they possess many carboxyl groups. During the electropolymerization of PEDOT in aqueous solution containing only EDOT monomer and CNTs, the negatively charged CNTs will act as dopants to balance the positive charge in the backbone of the PEDOT, and be embedded as part of the formed polymer. Fig. 1 shows the SEM images of the PEDOT/CNT coatings with different thickness. The CNTs were well dispersed and exhibited
Discussion
Chronic neural stimulation via microelectrode arrays has tremendous clinical potential in restoring lost or impaired neurological functions. As the current clinically applied electrode materials do not meet the challenge of chronic neural stimulation, the search for alternative materials that have higher charge injection capacity and long-term stability continues. Previously, PEDOT/PSS coating has been demonstrated to be a promising material for stimulation due to its low impedance, high charge
Conclusions
The present study demonstrates that PEDOT/CNT coatings can be electrochemically deposited on the Pt electrodes of microelectrode arrays. The coated electrodes exhibited much lower impedance, higher charge storage capacity, and a high charge injection limit of about 2.5 mC/cm2. The PEDOT/CNT coating displayed very high stability under both long-term biphasic pulse stimulation and aggressive cyclic voltammetric stimulation. In addition, it showed excellent in vitro biocompatibility. These
Acknowledgments
This research was financially supported in part by the National Institute of Health R01NS062019, the Department of Defense TATRC grant WB1XWH-07-1-0716, and the National Science Foundation Grants 0748001, 0729869. The authors would like to thank C. Byers for his assistance in performing some of the electrochemical testing described in this work.
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