The Neuroinflammatory Response to Nanopatterning Parallel Grooves into the Surface Structure of Intracortical Microelectrodes

Abstract

The smooth surface structure of intracortical microelectrodes implanted within the nanometer‐scale architecture of brain tissue may contribute to the foreign body response. Here, the neuroinflammatory response to nanopatterning surface grooves etched directly on nonfunctional Michigan‐style microelectrodes is explored. Rats implanted with nanopatterned silicon microelectrodes are compared to smooth control implants to observe the effects the grooves have on neuroinflammation. Histology and real‐time PCR at 2 and 4 weeks postimplantation quantify glial cell reactivity and activation, inflammation, oxidative stress, and neuronal survival. Histological observations of glial cells and blood–brain barrier permeability do not show appreciable differences between the nanopatterned and control implants. However, silicon microelectrodes with nanopatterned grooves have more high mobility group box 1 (HMGB1) gene expression at 2 weeks and less nitric oxide synthase (NOS2) gene expression at 4 weeks compared to control surfaces. Control samples have increased NOS2, HMGB1, and tumor necrosis factor gene expression from 2 to 4 weeks, while nanopatterned implants have significant decrease in CD14 gene expression from 2 to 4 weeks. Collectively the results indicate that etching nanopatterned grooves do not reduce histological markers of neuroinflammation compared to control implants, but gene expression results encourage further investigation.

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

“…Bérces et al demonstrated that neural cells preferred binding to each other rather than the nanopatterned silicon and platinum MEA surfaces. Also, a study performed by Ereifej et al tested the effects of nanopatterned parallel grooves (200 nm wide and 200 nm deep with 300 nm spacing between) on MEA biocompatibility, specifically through determination of the overall inflammatory response. Results indicated that in comparison to the control, nonpatterned, MEA surfaces, the nanopatterned grooves did not significantly reduce neuroinflammation.…”

“…It is also possible that the material from which the MEA is fabricated could compromise the biocompatibility and performance of the MEA even after its topographical alterations. Materials utilized to fabricate MEAs in most of the aforementioned studies59a,74,76,77,79 were primarily very stiff materials, such as platinum, silicon, glass, and stainless metals. Given neuronal cells have considerable difficulty in attaching to stiff surfaces, it comes to no surprise that success is not always guaranteed when applying surface topography enhancements to stiff substrates.…”

Investigating the Association between Motor Function, Neuroinflammation, and Recording Metrics in the Performance of Intracortical Microelectrode Implanted in Motor Cortex

“…Surgical procedures were similar to our previously published methods [ 12 , 20 , 40 , 41 ]. Six male Sprague Dawley rats (8–10 weeks old, ~225 gm) were implanted with silicon, single shank, 16 channel intracortical microelectrodes (NeuroNexus A1x16-3mm-100-177-Z16, NeuroNexus, Ann Arbor, MI, USA) in the primary motor cortex (2mm lateral to midline and 2mm anterior to bregma) for eight weeks.…”

“…Immunohistochemistry was utilized to quantify the tissue reaction for activated microglia, astrocytes, blood–brain barrier permeability, and total neurons directly around the electrode implant site. Standard immunohistochemistry protocols used in our lab were conducted on the sliced brain tissue [ 40 , 41 , 45 ]. Briefly, two frozen slides per animal (each containing three tissue slices from layers III and V of the cortex) were equilibrated to room temperature (RT) for one hour.…”

“…The GFAP antibody labels all astrocytes, immature, mature and reactive, thus normalizing the area around the implant site to the background tissue, which allows for the depiction of the reactive astrocytic response around the implanted microelectrode. Following which, the area under the curve in 50 µm increments was obtained using MATLAB and used in statistical analysis [ 40 ].…”