A Meta-Analysis of Intracortical Device Stiffness and Its Correlation with Histological Outcomes.

Allison Stiller,Joseph Pancrazio,Stuart Cogan,Aashika Ashok,Bryan Black,Victor Varner,Christopher Kung

doi:10.3390/mi9090443

Allison Stiller, Joseph Pancrazio + Show 5 more

Open Access

https://doi.org/10.3390/mi9090443

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Journal: Micromachines	Publication Date: Sep 6, 2018
Citations: 49	License type: CC BY 4.0

Affiliation: The University of Texas at Dallas

Abstract

Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess the correlation between device stiffness, a function of both material modulus and cross-sectional area, and the severity of immune response. Meta-analysis data were derived from nine previously published studies which reported device material and geometric properties, as well as histological outcomes. Device bending stiffness was calculated by treating the device shank as a cantilevered beam. Immune response was quantified through analysis of immunohistological images from each study, specifically looking at fluorescent markers for neuronal nuclei and astrocytes, to assess neuronal dieback and gliosis. Results demonstrate that the severity of the immune response, within the first 50 µm of the device, is highly correlated with device stiffness, as opposed to device modulus or cross-sectional area independently. In general, commercially available devices are around two to three orders of magnitude higher in stiffness than devices which induced a minimal tissue response. These results have implications for future device designs aiming to decrease chronic tissue response and achieve increased long-term functionality.

Highlights

Paralysis and limb loss pose significant personal, financial, and health burdens
Through quantitative analysis of previously published immunohistological images, we demonstrate that the severity of the immune response is highly correlated with device stiffness
For the purposes of this analysis, we focused on stains for neurons and astrocytes, neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP), a protein expressed in astrocytes

Summary

Introduction

Paralysis and limb loss pose significant personal, financial, and health burdens. Each year in the U.S alone, there are over 17,500 cases of spinal cord injury where less than 1% achieve complete recovery [1]. The nationwide prevalence of amputees is even higher at 185,000 new cases each year [2]. To address this issue, engineers and scientists are developing a range of technologies with the intent of bypassing the damaged component of the peripheral or central nervous system, to replace or restore lost motor function [3]. State-of-the-art devices are implanted intracortically, or directly into the brain, where they can record biopotentials associated with voluntary movement [4]. Neural data can be decoded and used to drive the movement of assistive devices and prosthetic limbs, or control stimulation for functional restoration of paralyzed limbs [5,6]

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