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Stable interconnection to neurons in vivo over long time-periods is critical for the success of future advanced neuroelectronic applications. The inevitable foreign body reaction towards implanted materials challenges the stability and an active intervention strategy would be desirable to treat inflammation locally. Here, we investigate whether controlled release of the anti-inflammatory drug Dexamethasone from flexible neural microelectrodes in the rat hippocampus has an impact on probe-tissue integration over 12 weeks of implantation. The drug was stored in a conducting polymer coating (PEDOT/Dex), selectively deposited on the electrode sites of neural probes, and released on weekly basis by applying a cyclic voltammetry signal in three electrode configuration in fully awake animals. Dex-functionalized probes provided stable recordings and impedance characteristics over the entire chronic study. Histological evaluation after 12 weeks of implantation revealed an overall low degree of inflammation around all flexible probes whereas electrodes exposed to active drug release protocols did have neurons closer to the electrode sites compared to controls. The combination of flexible probe technology with anti-inflammatory coatings accordingly offers a promising approach for enabling long-term stable neural interfaces.

Micro-sized electrodes are essential for highly sensitive communication at the neural interface with superior spatial resolution. However, such small electrodes inevitably suffer from high electrical impedance and thus high levels of thermal noise deteriorating the signal to noise ratio. In order to overcome this problem, a nanostructured Pt-coating was introduced as add-on functionalization for impedance reduction of small electrodes. In comparison to platinum black deposition, all used chemicals in the deposition process are free from cytotoxic components. The grass-like nanostructure was found to reduce the impedance by almost two orders of magnitude compared to untreated samples which was lower than what could be achieved with conventional electrode coatings like IrOx or PEDOT. The realization of the Pt-grass coating is performed via a simple electrochemical process which can be applied to virtually any possible electrode type and accordingly shows potential as a universal impedance reduction strategy. Elution tests revealed non-toxicity of the Pt-grass and the coating was found to exhibit strong adhesion to the metallized substrate.

Electrodes coated with the conducting polymer poly(3,4-ethylene dioxythiophene) (PEDOT) possess attractive electrochemical properties for stimulation or recording in the nervous system. Biomolecules, added as counter ions in electropolymerization, could further improve the biomaterial properties, eliminating the need for surfactant counter ions in the process. Such PEDOT/biomolecular composites, using heparin or hyaluronic acid, have previously been investigated electrochemically. In the present study, their biocompatibility is evaluated. An agarose overlay assay using L929 fibroblasts, and elution and direct contact tests on human neuroblastoma SH-SY5Y cells are applied to investigate cytotoxicity in vitro. PEDOT:heparin was further evaluated in vivo through polymer-coated implants in rodent cortex. No cytotoxic response was seen to any of the PEDOT materials tested. The examination of cortical tissue exposed to polymer-coated implants showed extensive glial scarring irrespective of implant material (Pt:polymer or Pt). However, quantification of immunological response, through distance measurements from implant site to closest neuron and counting of ED1+ cell density around implant, was comparable to those of platinum controls. These results indicate that PEDOT:heparin surfaces were non-cytotoxic and show no marked difference in immunological response in cortical tissue compared to pure platinum controls.

Conducting polymers (CPs) have frequently been described as outstanding coating materials for neural microelectrodes, providing significantly reduced impedance or higher charge injection compared to pure metals. Usability has until now, however, been limited by poor adhesion of polymers like poly(3,4-ethylenedioxythiophene) (PEDOT) to metallic substrates, ultimately precluding long-term applications. The aim of this study was to overcome this weakness of CPs by introducing two novel adhesion improvement strategies that can easily be integrated with standard microelectrode fabrication processes. Iridium Oxide (IrOx) demonstrated exceptional stability for PEDOT coatings, resulting in polymer survival over 10 000 redox cycles and 110 days under accelerated aging conditions at 60 °C. Nanostructured Pt was furthermore introduced as a purely mechanical adhesion promoter providing 10-fold adhesion improvement compared to smooth Pt substrates by simply altering the morphology of Pt. This layer can be realized in a very simple process that is compatible with any electrode design, turning nanostructured Pt into a universal adhesion layer for CP coatings. By the introduction of these adhesion-promoting strategies, the weakness of CP-based neural probes can ultimately be eliminated and true long-term stable use of PEDOT on neural probes will be possible in future electrode generations.

Electrodes intended for neural communication must be designed to meet both the electrochemical and biological requirements essential for long term functionality. Metallic electrode materials have been found inadequate to meet these requirements and therefore conducting polymers for neural electrodes have emerged as a field of interest. One clear advantage with polymer electrodes is the possibility to tailor the material to have optimal biomechanical and chemical properties for certain applications. To identify and evaluate new materials for neural communication electrodes, three charged biomolecules, fibrinogen, hyaluronic acid (HA), and heparin are used as counterions in the electrochemical polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting material is evaluated electrochemically and the amount of exposed biomolecule on the surface is quantified. PEDOT:biomolecule surfaces are also studied with static contact angle measurements as well as scanning electron microscopy and compared to surfaces of PEDOT electrochemically deposited with surfactant counterion polystyrene sulphonate (PSS). Electrochemical measurements show that PEDOT:heparin and PEDOT:HA, both have the electrochemical properties required for neural electrodes, and PEDOT:heparin also compares well to PEDOT:PSS. PEDOT:fibrinogen is found less suitable as neural electrode material.

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