Friday, April 19, 2024
4/19/2024
The Capadona group has identified the role of inflammation-mediated oxidative stress products in microelectrode-initiated neuroinflammation to be the most comprehensive source contributing to poor electrode reliability. In order to realize the potential of any application using intracortical microelectrodes, we must minimize the degradative side effects caused by oxidative stress products, without inhibiting the beneficial wound healing aspects of inflammation. We have used a variety of antioxidant treatments to demonstrate a reduction in intracortical microelectrode-mediated oxidative stress and preserve neuron viability. Our most promising strategy to date for improving intracortical recording reliability is our biomimetic antioxidative coating. Our initial efforts focused on planar silicon substrates for ease of characterization, cost, and their recent popularity in the literature. Our preliminary data suggest that our novel antioxidative-coated microelectrodes reduce the initial inflammatory response, preserve neuron populations, and improve initial recording quality. The initial mimetic coating is not a comprehensive antioxidative strategy. Oxidative stress can be initiated by either a damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs) pathway. In the proposed study, we will specifically investigate the effect that antioxidant-coated microelectrodes have on the stability of stimulation and neural recordings. Our electrodes will be coated with antioxidants that target either PAMP, DAMP, or both PAMP and DAMP pathways, in order to develop a comprehensive, but not overly suppressive approach. In order to be applicable to on-going clinical trials, our coating must also be translatable to the only penetrating recording microelectrode approved by the US FDA. Therefore, we have shown that these antioxidants can be attached to Parylene C. The innovation of this proposal is in the application of a platform approach to surface modify Parylene C coated Blackrock Arrays, to effectively minimize two of the leading causes of intracortical microelectrode failure: materials damage and biological damage. On a more fundamental level, this work will also examine how varying the dimensions of intracortical microelectrodes impacts both ROS and the tissue response. Extremely thin devices, regardless of inherent Young's modulus of the constituent material, become very flexible. Due to its high fracture resistance, we will leverage amorphous silicon carbide to create microelectrode probes with small thicknesses. Such probes will enable us to test the hypothesis that oxidative stress and neuroinflammation are proportional to the device dimension and resulting rigidity. We will further demonstrate that the associated oxidative stress and neuroinflammation generated from larger more rigid devices can be subdued by coating the implant with antioxidants.
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