The use of intracortical microelectrode arrays has gained significant attention in being able to help restore function in paralysis patients and study the brain in various neurological disorders. Electrode implantation in the cortex causes vasculature or blood-brain barrier (BBB) disruption and thus elicits a foreign body response (FBR) that results in chronic inflammation and may lead to poor electrode performance. In this study, a comprehensive insight into the acute molecular mechanisms occurring at the Utah electrode array-tissue interface is provided to understand the oxidative stress, neuroinflammation, and neurovascular unit (astrocytes, pericytes, and endothelial cells) disruption that occurs following microelectrode implantation. Quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify the gene expression at acute time-points of 48-hr, 72-hr, and 7-days for factors mediating oxidative stress, inflammation, and BBB disruption in rats implanted with a non-functional 4×4 Utah array in the somatosensory cortex. During vascular disruption, free iron released into the brain parenchyma can exacerbate the FBR, leading to oxidative stress and thus further contributing to BBB degradation. To reduce the free iron released into the brain tissue, the effects of an iron chelator, deferoxamine mesylate (DFX), was also evaluated.

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Brain machine interfaces (BMIs), introduced into the daily lives of individuals with injuries or disorders of the nervous system such as spinal cord injury, stroke, or amyotrophic lateral sclerosis, can improve the quality of life. BMIs rely on the capability of microelectrode arrays to monitor the activity of large populations of neurons. However, maintaining a stable, chronic electrode–tissue interface that can record neuronal activity with a high signal-to-noise ratio is a key challenge that has limited the translation of such technologies. An electrode implant injury leads to a chronic foreign body response that is well-characterized and shown to affect the electrode–tissue interface stability. Several strategies have been applied to modulate the immune response, including the application of immunomodulatory drugs applied both systemically and locally. While the use of passive drug release at the site of injury has been exploited to minimize neuroinflammation, this strategy has all but failed as a bolus of anti-inflammatory drugs is released at predetermined times that are often inconsistent with the ongoing innate inflammatory process. Common strategies do not focus on the proper anchorage of soft hydrogel scaffolds on electrode surfaces, which often results in delamination of the porous network from electrodes. In this study, we developed a microwire platform that features a robust yet soft biocompatible hydrogel coating, enabling long-lasting drug release via formation of drug aggregates and dismantlement of hydrophilic biodegradable three-dimensional polymer networks. Facile surface chemistry is developed to functionalize polyimide-coated electrodes with the covalently anchored porous hydrogel network bearing large numbers of highly biodegradable ester groups. Exponential long-lasting drug release is achieved using such hydrogels. We show that the initial state of dexamethasone (Dex) used to formulate the hydrogel precursor solution plays a cardinal role in engineering hydrophilic networks that enable a sustained and long-lasting release of the anti-inflammatory agent. Furthermore, utilization of a high loading ratio that exceeds the solubility of Dex leads to the encapsulation of Dex aggregates that regulate the release of this anti-inflammatory agent. To validate the anti-inflammatory effect of the hydrogel-functionalized Dex-loaded microwires, an in vivo preliminary study was performed in adult male rats (n = 10) for the acute time points of 48 h and 7 days post implant. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the mRNA expression of certain inflammatory-related genes. In general, a decrease in fold-change expression was observed for all genes tested for Dex-loaded wires compared with controls (functionalized but no drug). The engineering of hybrid microwires enables a sustained release of the anti-inflammatory agent over extended periods of time, thus paving the way to fabricate neuroprosthetic devices capable of attenuating the foreign body response.