Strain-induced scarring & its effects on microelectrodes

描述（由申请人提供）：硅微电极阵列技术在推进开发稳定的电极-脑接口的目标方面具有相当大的前景。来自大脑中多个神经元的慢性单位记录将显著增强我们对正常生理学的理解，并为神经假肢装置的使用提供有价值的控制信号。然而，当前一代的硅微电极不允许稳定的长期记录。导致硅微电极介导记录失败的确切机制尚不清楚。我们假设硅和神经组织之间百万倍的刚度不匹配在界面处产生剪切力，导致星形胶质瘢痕形成，逐渐将神经元排除在记录电极附近。为了验证我们的假设，我们提出了新的和创新的方法来a)确定原代星形胶质细胞的应变敏感性，就其采用瘢痕表型而言；b)确定硅微电极周围的应变诱导瘢痕形成是否会降低其在器官型海马切片培养中的记录能力；c)为硅微电极设计涂层，允许抗炎剂的持续局部释放，以减少疤痕和增加记录的稳定性。上述目标代表了对稳定神经假体装置设计和开发中的一个重要问题的高度跨学科的研究。我们的研究目标的成功完成可能会影响下一代硅微电极阵列设计的机械和生化方面，并随后显著影响残疾人的生活质量。

DESCRIPTION (provided by applicant): Silicon microelectrode array technology holds considerable promise in advancing the goal of developing stable, electrode-brain interfaces. Chronic unit recordings from multiple neurons in the brain would significantly enhance our understanding of normal physiology and provide a valuable control signal for use in neuro-prosthetic devices. However, the current generation of silicon microelectrodes does not allow stable long-term recordings. The precise mechanisms that cause failure of silicon microelectrode mediated recordings are not known. We hypothesize that the million-fold stiffness mismatch between silicon and neural tissues generates shearing forces at the interface resulting in an astro-glial scar formation that progressively excludes neurons from the vicinity of the recording electrodes. To test our hypothesis, we propose novel and innovative methods to a) determine the strain-sensitivity of primary astrocytes in terms of their adopting a scarring phenotype; b) determine if strain-induced scar formation around Si-microelectrodes degrades their recording capabilities in organotypic hippocampal slice cultures; and c) design coatings for Si-microelectrodes that allow the sustained local release of anti-inflammatory agents to decrease scarring and increase recording stability. The above aims represent a highly inter-disciplinary investigation of an important problem in the design and development of stable neuro-prosthetic devices. Successful completion of our research goals is likely to impact the mechanical and biochemical aspects of the design of the next generation of silicon microelectrode arrays, and subsequently significantly impact the quality of life of persons with disabilities.