Characterizing and Mitigating the Role of Oxidative Damage in Microelectrode Failure

表征和减轻氧化损伤在微电极失效中的作用

• 批准号: 10599364
• 负责人: Jeffrey R Capadona
• 金额: $ 58.11万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599364
• 关键词: Animal Experiments; Animals; Antioxidants; Area; Behavior; Biological; Biomimetics; Blood - brain barrier anatomy; Cells; Characteristics; Charge; Chemistry; Chronic; Clinical; Clinical Trials; Complex; Corrosion; Data; Deposition; Detection; Development; Device Removal; Devices; Dimensions; Electrodes; Event; Exhibits; Failure; Foreign Bodies; Fracture; Gene Expression; Geometry; Gliosis; Histology; Human; Implant; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Injections; Literature; Long-Term Effects; Measurement; Mediating; Microelectrodes; Microglia; Modification; Modulus; Molecular; Monitor; Nerve Degeneration; Neurons; Oxidative Stress; Oxygen; Pathway interactions; Pattern; Penetration; Performance; Periodicity; Play; Population; Protocols documentation; Rattus; Reactive Oxygen Species; Resistance; Roentgen Rays; Role; Scanning Electron Microscopy; Silicon; Site; Source; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Structure; Surface; Technology; Testing; Thick; Thinness; Time; Tissues; Utah; Work; clinically relevant; cost; design; electric impedance; extracellular; flexibility; implant coating; implantation; improved; in vivo; infrared spectroscopy; innovation; insight; microstimulation; mimetics; neural; neuroinflammation; novel; oxidative damage; parylene C; pathogen; preservation; prevent; response; side effect; silicon carbide; surface coating; voltage; wound healing

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.

Capadona小组已经确定了炎症介导的氧化应激产物在 微电极引发的神经炎症是导致不良反应的最全面的来源。 电极可靠性为了实现使用皮质内微电极的任何应用的潜力， 我们必须最大限度地减少氧化应激产物引起的降解副作用，而不抑制 有利于伤口愈合方面的炎症。 我们已经使用了各种抗氧化剂治疗，以证明减少皮质内 微电极介导的氧化应激和保护神经元活力。我们最有希望的策略 提高皮质内记录可靠性的最新数据是我们的仿生抗氧化涂层。我们最初 努力集中在平面硅衬底上，以便于表征、成本和它们最近的流行 在文献中。我们的初步数据表明，我们的新型抗氧化涂层微电极减少 初始炎症反应，保护神经元群体，并提高初始记录质量。 最初的模拟涂层不是一个全面的抗氧化策略。氧化应激可以是 由损伤相关分子模式（DAMP）或病原体相关分子模式（DAMPs）启动 模式（PAMPs）通路。在拟议的研究中，我们将专门研究 抗氧化剂涂层微电极对刺激和神经记录的稳定性有影响。我们 电极将涂有抗氧化剂，抗氧化剂针对PAMP、DAMP或PAMP和DAMP两者 途径，以制定一个全面的，但不是过度抑制的方法。 为了适用于正在进行的临床试验，我们的涂层还必须可转换为唯一的 美国FDA批准的穿透记录微电极。因此，我们已经表明，这些 抗氧化剂可以连接到聚对二甲苯C上。该提案的创新之处在于应用了一种 表面改性聚对二甲苯C涂覆的Blackrock阵列的平台方法，以有效地最小化两个 皮质内微电极失效的主要原因是材料损伤和生物学损伤。 在更基本的层面上，这项工作还将研究如何改变皮质内的尺寸， 微电极影响ROS和组织反应。超薄设备，无论 组成材料的固有杨氏模量，变得非常灵活。由于其高度断裂 电阻，我们将利用无定形碳化硅来制造具有小 厚度。这种探针将使我们能够测试氧化应激和 神经炎症与装置尺寸和产生的刚性成比例。我们将进一步 证明了相关的氧化应激和神经炎症产生于更大的更刚性的 可以通过用抗氧化剂涂覆植入物来抑制装置。