Mechanical Flexibility Reduces the Foreign Body Response to Long-Term Implanted Microelectrodes in Rabbit Cortex

Abstract

Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive microelectrodes. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We compared the glial response over a 26–96 week period following implantation in the rabbit cortex of microwires and a novel flexible electrode. Horizontal sections were used to obtain a depth profile of the radial distribution of microglia, astrocytes and neurofilament. We found that the flexible electrode was associated with decreased gliosis compared to the microwires over these long indwelling periods. This was in part due to a decrease in overall microgliosis and enhanced neuronal density around the flexible probe, especially at longer periods of implantation.

A Critical Review of Microelectrode Arrays and Strategies for Improving Neural Interfaces

“…Thereby, to increase MEA mechanical compliance, polymers are frequently used, as they can achieve a significantly lower Young's modulus in comparison to metals, and elasticity can be introduced into the material. Sohal et al compared the severity of the FBR elicited when implanting two different types of MEAs into the brains of white rabbits: a stiff, nonflexible microwire MEA and a flexible, Parylene‐C sinusoidal MEA. Both microglial and astrocytic responses were significantly lowered for the flexible sinusoidal MEA compared to the nonflexible microwire MEA surrounding the site of implantation.…”

“…Nevertheless, various modifications to MEAs have been shown to be highly successful in reducing the resulting FBR following MEA insertion and improving their performance. Applying modifications to surface chemistry, topography,59a,61,67b stiffness, and geometry [81,86,90a] of MEAs have all been shown to be highly promising for improving MEA biocompatibility.…”

Neuroadhesive L1 coating attenuates acute microglial attachment to neural electrodes as revealed by live two-photon microscopy

“…This includes changing the footprint of the probe or the probe’s electrode sites [18,36,44,47–51,160], altering recording site materials [48,52–57], applying flexible geometries or soft materials [26,27,36,58–62,161,162], creating dissolvable insertion shuttles for softer probe materials [63], locally delivering anti-inflammatory or neuroprotective drugs [64–75], and modifying the probe’s surface chemistry [36,76–78]. …”

Long-term in vivo Monitoring of Gliotic Sheathing of Ultrathin Entropic Coated Brain Microprobes with Fiber-based Optical Coherence Tomography

“…To realize a long-term reliable neuro-electrode interface, it seems essential to minimize the foreign body response (Nguyen et al, 2014;Potter et al, 2014;Sohal, Clowry, Jackson, O'Neill, & Baker, 2016;Winslow & Tresco, 2010). To this end, many approaches have been proposed and investigated including innovations on bio-compatible flexible materials (Luan et al, 2017;Nguyen et al, 2014;Richter et al, 2013;Rousche et al, 2001;Rubehn, Lewis, Fries, & Stieglitz, 2010;Sohal et al, 2016;Stieglitz & Meyer, 1998;Takeuchi, Suzuki, Mabuchi, & Fujita, 2004;Böhler et al, 2017), decreasing implant size (Khilwani et al, 2017;Patel et al, 2015Patel et al, , 2016Ferro et al, 2018) or surface modifications by coating the device with anti-inflammatory drugs that will actively release (Azemi, Lagenaur, & Cui, 2011;Boehler et al, 2017;Eles et al, 2017;Kolarcik et al, 2012;Potter et al, 2014).…”