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Effects of dip-coated films on the properties of implantable intracortical microelectrodes.

机译：浸涂膜对植入式皮层内微电极性能的影响。

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摘要

The successful clinical use of implantable intracortical microelectrodes (ICMs) to treat certain types of deafness, blindness, and paralysis is limited by a reactive tissue response (RTR) of the brain. This RTR culminates in the formation of a tight glial scar and a loss of neuronal density around implanted ICMs, and is accompanied by a decrease in signal to noise ratio and an increase in impedance. While no comprehensive mechanistic understanding of the underlying biology is currently agreed upon in the field, a general consensus exists around a highly volatile acute RTR phase. During this acute phase, the electrical properties of ICMs do not always coincide with cellular responses, and the extent of initial injury appears to greatly influence the degree of the chronic RTR. While many electrode modifications and treatments are effective in the short term, the chronic RTR appears impervious to most interventions. To better understand the acute phase of the RTR, this dissertation aims to investigate the effects of various dip-coated biomolecules on the electrical properties of ICMs and cellular responses to microscale ICM-like foreign bodies. We first present an examination of silica sol-gel thin films as a potential biomolecule delivery platform which does not adversely affect the electrical properties of ICMs. The second study shows that adsorbed proteins, thought to play an important role in modulating the RTR, cause significant increases in electrode impedance. In contrast to prevalent electrical models of the electrode tissue interface which assume purely resistive impedance changes due to adsorbed proteins, our results show both resistive and capacitive changes. We also show that increases in impedance related to protein adsorption can be prevented by dip coating ICMs in an aqueous solution of high molecular weight polyethylene glycol (PEG). We then describe a method to clean electrode sites using direct current (DC) biasing, showing that DC biasing is capable of restoring electrode impedance following exposure to enzymatic cleaning solutions, proteins, phantom brains, and actual brain tissue. The final study in an in vitro mixed primary cortical cell culture model shows that lipopolysaccharide (LPS), a well-known ligand to toll-like 4 (TL4) receptors, dip-coated onto segments of metal microwire, can simulate localized inflammation around an implanted ICM. We observe elevated activation of glial cells in interface regions, and extending into more distant regions. This elevation in glial responses is not accompanied by a decrease in neuronal density. We additionally show that microwire dip-coated with a mixture of LPS and PEG exhibits significantly lower microglial and astrocyte responses. These findings highlight the importance of adsorbed proteins, some of which are implicated in aggravating the reactive tissue response, but which we show can result in significant increases in electrode impedance before the RTR even begins. These impedance changes can be prevented through the use of dip-coated PEG. Our cell culture data presents further evidence for the attractiveness of TL4 receptors as a target for intervention, and suggests that the loss of neuronal density observed in vivo is better explained by other mechanisms following device insertion than pure glial activation.
机译：可植入的皮质内微电极（ICM）用于治疗某些类型的耳聋，失明和麻痹的成功临床应用受到大脑反应性组织反应（RTR）的限制。该RTR最终导致紧密的神经胶质疤痕的形成和植入的ICM周围神经元密度的损失，并伴随着信噪比的降低和阻抗的增加。尽管目前在该领域尚未达成对基础生物学的全面机械理解，但围绕高度挥发性的急性RTR阶段仍存在普遍共识。在此急性期，ICM的电特性并不总是与细胞反应一致，并且初始损伤的程度似乎极大地影响了慢性RTR的程度。尽管许多电极修饰和治疗在短期内有效，但慢性RTR似乎不受大多数​​干预措施的影响。为了更好地了解RTR的急性期，本论文旨在研究各种浸涂生物分子对ICM的电学性质和细胞对微尺度ICM样异物的反应的影响。我们首先介绍了一种二氧化硅溶胶-凝胶薄膜作为一种潜在的生物分子传递平台的研究，该平台不会对ICM的电性能产生不利影响。第二项研究表明，被认为在调节RTR中起重要作用的吸附蛋白会导致电极阻抗显着增加。与电极组织界面的普遍电学模型（假定由于吸附的蛋白质导致的纯电阻性阻抗变化）相反，我们的结果显示了电阻性和电容性变化。我们还表明，可以通过在高分子量聚乙二醇（PEG）水溶液中浸涂ICM来防止与蛋白质吸附有关的阻抗增加。然后，我们描述了一种使用直流（DC）偏压清洁电极部位的方法，显示了直流偏压能够在暴露于酶促清洁溶液，蛋白质，幻影脑和实际的脑组织后恢复电极阻抗。体外混合原代皮层细胞培养模型的最终研究表明，脂多糖（LPS）是toll样4（TL4）受体的著名配体，浸涂在金属微丝的片段上，可以模拟周围的局部炎症。植入ICM。我们观察到界面区域神经胶质细胞的活化增强，并延伸到更远的区域。神经胶质反应的这种升高并不伴有神经元密度的降低。我们还表明，用LPS和PEG的混合物浸涂的微丝表现出明显更低的小胶质细胞和星形胶质细胞反应。这些发现突出了吸附蛋白的重要性，其中一些蛋白与加剧反应性组织反应有关，但我们证明，在RTR开始之前，可导致电极阻抗的显着增加。这些阻抗变化可以通过使用浸涂PEG来防止。我们的细胞培养数据为TL4受体作为干预靶点的吸引力提供了进一步的证据，并表明在装置插入后，其他机制比单纯的神经胶质细胞活化更好地解释了体内观察到的神经元密度的丧失。

著录项

  • 作者

    Sommakia, Salah.;

  • 作者单位

    Purdue University.;

  • 授予单位 Purdue University.;
  • 学科 Engineering Biomedical.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 136 p.
  • 总页数 136
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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