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 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 concentrations of these soluble factors surrounding the implant will reduce the severity of the FBR.
To explore this hypothesis and identify design inputs that engineers can utilize to improve next generation devices, we propose to study the FBR to a series of novel test devices based on single-shank, Michigan-style microelectrode arrays. These devices will have modified architectures and altered constitutive properties intended to reduce macrophage activation and/or the impact of their secreted factors. To further facilitate the design and testing of these devices, we will (1) create a series of 3-D finite element simulations to predict the distributions of various macrophage-secreted factors around virtual device designs with altered architectures and permeability. (2) Using quantitative immunohistochemical approaches and imaging MALDI mass spectrometry, we will test the efficacy of reducing the amount of device surface area presented for macrophage interaction/activation in altering the brain FBR. (3) Using similar techniques as in aim two; we will examine 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. Findings from these studies will provide essential design inputs and computational tools to improve device biocompatibility and drive the creation of next generation microelectrode recording devices.