| 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). |
