Department of Bioengineering, The University of Texas at Dallas, 800 W Campbell Rd, Richardson, TX, 75080, United States.
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, United States; Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd, Cleveland, OH, 44106, United States.
Biomaterials. 2023 Dec;303:122351. doi: 10.1016/j.biomaterials.2023.122351. Epub 2023 Nov 1.
Intracortical microelectrode arrays (MEAs) are used to record neural activity. However, their implantation initiates a neuroinflammatory cascade, involving the accumulation of reactive oxygen species, leading to interface failure. Here, we coated commercially-available MEAs with Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), to mitigate oxidative stress. First, we assessed the in vitro cytotoxicity of modified sample substrates. Then, we implanted 36 rats with uncoated, MnTBAP-coated ("Coated"), or (3-Aminopropyl)triethoxysilane (APTES)-coated devices - an intermediate step in the coating process. We assessed electrode performance during the acute (1-5 weeks), sub-chronic (6-11 weeks), and chronic (12-16 weeks) phases after implantation. Three subsets of animals were euthanized at different time points to assess the acute, sub-chronic and chronic immunohistological responses. Results showed that MnTBAP coatings were not cytotoxic in vitro, and their implantation in vivo improved the proportion of electrodes during the sub-chronic and chronic phases; APTES coatings resulted in failure of the neural interface during the chronic phase. In addition, MnTBAP coatings improved the quality of the signal throughout the study and reduced the neuroinflammatory response around the implant as early as two weeks, an effect that remained consistent for months post-implantation. Together, these results suggest that MnTBAP coatings are a potentially useful modification to improve MEA reliability.
皮层内微电极阵列 (MEA) 用于记录神经活动。然而,它们的植入会引发神经炎症级联反应,涉及活性氧物质的积累,导致界面失效。在这里,我们用 Mn(III)四(4-苯甲酸)卟啉 (MnTBAP) 修饰市售的 MEA,以减轻氧化应激。首先,我们评估了修饰后的样品基底的体外细胞毒性。然后,我们将 36 只大鼠植入未涂层、MnTBAP 涂层(“涂层”)或(3-氨丙基)三乙氧基硅烷 (APTES) 涂层的设备中——这是涂层过程的中间步骤。我们在植入后 1-5 周的急性、6-11 周的亚慢性和 12-16 周的慢性阶段评估电极性能。三组动物在不同时间点安乐死,以评估急性、亚慢性和慢性免疫组织学反应。结果表明,MnTBAP 涂层在体外没有细胞毒性,体内植入可以提高亚慢性和慢性阶段电极的比例;APTES 涂层会导致神经界面在慢性阶段失效。此外,MnTBAP 涂层改善了整个研究过程中的信号质量,并早在植入后两周就减少了植入周围的神经炎症反应,这种效果在植入后数月内仍然保持一致。总之,这些结果表明 MnTBAP 涂层是一种提高 MEA 可靠性的潜在有用的修饰方法。