The degradation of glial scar and enhancement of chronic intracortical recording electrode performance through the local delivery of dexamethasone and chondroitinase

[摘要] The ability of conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) to store a drug as a dopant and release it following electrical stimulus make them an intriguing coating possibility for intracortical electrodes, along with their ability to reduce electrode impedance. The mechanism allows for the release of an assortment of useful agents, including anti-inflammatory drugs and neuromodulatory chemicals. We evaluated the release capabilities of a multi-walled carbon nanotube (MWCNT)-doped PEDOT coating incorporating the anti-inflammatory steroid dexamethasone in vitro using sputtered-gold macroelectrodes, and then applied the coating to half of the electrodes within 16-shank platinum/iridium floating microelectrode arrays for chronic in vivo evaluation in rat visual cortex. Impedance measurement, neurophysiological recording, and cyclic voltammetric release stimulus (-0.9 V to 0.6 V, 1 V/s, 20 cycles) was performed daily to all channels. On the 11th day, histology was performed to quantitatively characterize inflammatory tissue response using OX42 (microglia) and GFAP (astroglia). Equivalent circuit analysis was performed to assist the interpretation of impedance data. Our results indicated that the MWCNT/PEDOT-coated gold macroelectrodes released double the amount of dexamethasone using passive release followed by CV stimulation (10 sets of 20 cycles) compared to passive release alone. Coatings applied to Pt/Ir microelectrodes reduced 1 kHz impedance in PBS by approximately 38%. Coated probes in vivo exhibited a significant decrease in 1 kHz impedance for the initial three days of implantation followed by an increase, between days 4 and 7, to values equivalent to those exhibited by uncoated probes. Neurophysiological recording performance of coated and uncoated probes remained equivalent for the duration of the experiment, in terms of signal-to-noise ratio and noise amplitude.Histology revealed no significant difference in tissue inflammatory response to coated and uncoated electrodes. Explant imaging revealed the presence of a membranous film enveloping coated electrodes, and equivalent circuit analysis suggested that the day 4-7 increase in 1 kHz impedance of coated electrodes was due to a decrease in effective surface area of the coatings as well as the core electrodes. Additional work was also performed developing a model for the in vivo microinjection of the enzyme Chondroitinase ABC into tissue surrounding implanted microelectrodes.

[发布机构] the University of Pittsburgh