Novel design strategies to reduce the foreign body response to central nervous system implants

Update Item Information
Title Novel design strategies to reduce the foreign body response to central nervous system implants
Publication Type dissertation
School or College College of Engineering
Department Biomedical Engineering
Author Skousen, John Lawrence
Date 2013-05
Description Multiple studies have shown the potential for using implantable microelectrode arrays to record consciously modulated neural signals and to restore volitional control of external devices to patients suffering from various nervous system and motor disorders. However, despite the promising potential of this technology, achieving widespread clinical application requires improving recording consistency and quality over a clinically relevant time frame. There is near consensus in the field that the foreign body response (FBR) that the brain mounts against implanted devices contributes to the observed recording instability. Available evidence suggests that pro-inflammatory and cytotoxic soluble factors secreted by reactive macrophages/microglia at the device-tissue interface mediate the cellular-level changes underlying the FBR. Based on this assumption, we hypothesize that implant designs that passively reduce the activation of these cells and the concentrations of their released soluble factors surrounding the implant will reduce the severity of the FBR. To explore this hypothesis we have studied the FBR to a series of novel test devices based on single-shank, Michigan-style microelectrode arrays. These devices have modified architectures and altered constitutive properties intended to reduce macrophage activation and/or the impact of their secreted factors. To facilitate the design and testing of these devices, we first created a series of three-dimensional (3-D) finite element simulations to predict the distributions of various macrophage-secreted factors around virtual device designs with altered architectures and permeability (Chapter 2). Building on predictions from these models, we have tested the efficacy of reducing the amount of device surface area presented for macrophage interaction/activation in altering the brain FBR (Chapter 3). Furthermore, we also examined the efficacy of increasing device permeability in altering the brain FBR by incorporating coatings that serve as cytokine sinks to passively absorb pro-inflammatory factors into the device and away from adjacent brain tissue (Chapter 4). In the final portion of this dissertation we move from these passive methods of limiting the extent and impact of activated inflammatory cells and describe the creation of extracellular matrix (ECM) based device coatings to bioactively reduce the FBR and drive improved healing and integration into tissue (Chapter 5).
Type Text
Publisher University of Utah
Subject Extracellular Matrix; Foreign Body Response; Inflammation; Macrophage; Microelectrode; Microglial
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Rights Management Copyright © John Lawrence Skousen 2013
Format application/pdf
Format Medium application/pdf
Format Extent 2,373,872 bytes
ARK ark:/87278/s6v12knx
Setname ir_etd
ID 195806
Reference URL https://collections.lib.utah.edu/ark:/87278/s6v12knx
Back to Search Results