Anti-inflammatory coatings on flexible neural probes in the cortex: A chronic in vivo study

摘要

Introduction: We here report on the effect of actively releasing the anti-inflammatory drug Dexamethasone from neural microelectrodes aiming at attenuating the immune reaction of the host tissue towards the implanted probe and thereby improving the long-term performance of such electrodes. Materials and Methods: Dexamethasone was stored in a conducting polymer coating (PEDOT) deposited on the recording sites of a flexible polyimide shaft-probe and released on demand by applying a cyclic voltammetry trigger signal on a weekly basis during 12 weeks of implantation in the rat hippocampus. The polymer coated contact sites were simultaneously used for recording of LFPs and electrochemical impedance spectroscopy in vivo. After 12 weeks of implantation, the tissue was fixated with the electrodes still in place and horizontally sectioned for immunohistological analysis with respect to glial scarring and neuron degeneration around the drug eluting probes as well as non-functionalized peers. Results and Discussion: We were able to record signals from anti-inflammatory functionalized probes during chronic implantation over 12 weeks and from 12 animals demonstrating that the drug eluting coating did not interfere with the overall recording properties of the neural electrodes. Impedance measurements collected over this time frame confirmed that the PEDOT coating remained electrochemically stable throughout the entire test period and that the drug eluting film did not delaminate from the IrOx substrate. Using a 10μm thin flexible polyimide probe further enabled us to keep the electrode in the tissue during the cryo sectioning and the subsequent immunohistological analysis so that alterations in the tissue could directly be related to specific contact sites along the electrode shaft. The flexible probes thereby showed an overall low degree of inflammation after 12 weeks of implantation, while the ED1-staining revealed the lowest macrophage concentration for the Dexamethasone probes. We could furthermore not identify the clear neuronal kill zone in front of the electrodes, which would have been expected as a consequence of a severe inflammatory reaction and is frequently reported by others. The absence of such a kill zone is encouraging and an indication that neither the probe itself nor the application of cyclic voltammetry nor the electrical impedance measurement or the actively released Dexamethasone had any detrimental effect on the host tissue. Conclusion: We could successfully demonstrate in a chronic animal experiment that flexible neural probes, functionalized with an anti-inflammatory coating, provide a promising strategy for keeping the glial scarring around an electrode at a low level. This finding holds promise for a future where reliable long term stable recording and stimulation of neurons is enabled by flexible anti-inflammatory probes.