Abstract
Stable interconnection to neurons invivo 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.
Highlights
The development of implantable microelectrodes has revolutionized the field of biomedical applications by enabling bidirectional communication with neural tissue at high resolution
Quantification of released Dex by high performance liquid chromatography (HPLC) analysis thereby revealed a total amount of 805 ng of Dex being released within 45 days. 24% of this mass were attributed to actively triggered release within 0.006% of the total experiment time, demonstrating a substantial release in response to the cyclic voltammetry (CV) sweeps compared to purely passive drug elution
The largest drug expulsion was found during the first trigger event (114 ng) while subsequent release events featured an to calculate the charge storage capacity (CSC) by integrating the total area under the CVcurves which provides a measure for the electrode status
Summary
The development of implantable microelectrodes has revolutionized the field of biomedical applications by enabling bidirectional communication with neural tissue at high resolution. Boehler et al / Biomaterials 129 (2017) 176e187 during the formation of the scar tissue or whether they eventually degenerate by other means in this process This chronic inflammation state and the loss of close-by neurons impairs the long-term functionality of microelectrodes and leads to reduction of recorded signal quality. Under these conditions, electrical stimulation parameters need to be continuously adjusted to retain efficient tissue activation over time [10,11,17,18]. Variations in probe geometries and implantation techniques were further not found to result in improved chronic tissue response [21e23]
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