Novel Bioactive Coatings for Chronically Implanted MEMS based Moveable Microelect

描述(申请人提供)：皮质神经假体是一种很有前途的方法，可以缓解一系列神经退行性疾病的症状，从阿尔茨海默氏症和帕金森氏症到瘫痪的脑创伤损伤，如中风。这些设备的一个主要障碍是在慢性条件下信号质量缓慢恶化，主要原因是(1)对脑组织的机械损伤，(2)源于神经炎症过程的生物排斥，以及(3)神经元与神经接口处的电极断开。本研究方案的总体目标是开发一种策略，用于维持神经-电极接口连接，并使用先前开发的基于MEMS的可移动微电极阵列来改善信号质量。目前的方法试图通过在各种聚合物基质中加入抗炎生物化学物质作为微电极周围的涂层来减少炎症并鼓励神经连接。主要的焦点一直是通过生物化学释放来抑制炎症。在这里，我们建议更进一步，试图通过调节包裹多晶硅可移动微电极的水凝胶涂层的机械性能来防止机械损伤和最大限度地减少炎症。我们将测试这样一个假设，即包裹在具有类似脑组织粘弹性特性的水凝胶涂层中的多晶硅微电极将对组织造成较小的应变，从而在慢性条件下减少神经炎症并改善信号质量。最终目标是开发一种复合水凝胶，防止机械损伤，并在慢性条件下保持功能神经界面。为了实现这一目标，具体目标是(1)确定胶囊化水凝胶的交联密度和相关硬度是否将胶质增生和脑组织损伤降至最低；(2)确定电极移动和在水凝胶涂层中加入NGF等生化物质是否将促进更好的神经连接和改善信号质量。水凝胶涂层微电极对脑组织的影响将通过慢性条件下的啮齿动物模型来表征，使用组织学、电学和机械方法来测试神经炎症的减少。利用不同涂层微电极的力位移数据，我们将生成一个基于有限元的慢性条件下脑组织的超弹性模型。此外，我们将使用电生理和组织学特征来描述在慢性条件下电极移动和水凝胶中包含的神经生长因子(NGF)的协同使用。这一提议的成功结果将需要开发长期植入神经假体设备的新策略，并更好地了解慢性条件下微电极对脑材料特性的影响。

DESCRIPTION (provided by applicant): Cortical neural prostheses are a promising approach to alleviate symptoms for a wide range of neurodegenerative disorders, ranging from Alzheimer's and Parkinson's disease to paralyzing brain trauma injuries, such as stroke. A major impediment in these devices is the slow deterioration of signal quality under chronic conditions mainly due to (1) mechanical damage to the brain tissue, (2) biological rejection stemming from neuroinflammation processes, and (3) disconnection of neurons from the electrode at the neural interface. The overall objective of this research proposal is to develop a strategy for maintaining the neural-electrode interface connection and improve signal quality using a previously developed MEMS based moveable microelectrode array. Current approaches attempt to reduce inflammation and encourage neural connectivity by incorporating anti-inflammatory biochemicals in various polymer-matrices as coatings surrounding the microelectrodes. The primary focus has been to suppress inflammation via biochemical release. Here we propose to take a step further and attempt to prevent mechanical damage and minimize inflammation by tuning the mechanical properties of a hydrogel coating encapsulating a polysilicon moveable microelectrode. We will test the hypothesis that polysilicon microelectrodes encapsulated in a hydrogel coating with similar viscoelastic properties of brain tissue will cause less strain on the tissue, leading to less neuroinflammation and improved signal quality under chronic conditions. The ultimate goal is to develop a composite hydrogel that prevents mechanical damage and maintains a functional neural interface under chronic conditions. To achieve this goal, the specific aims are (1) to determine whether the crosslinking density and related stiffness of an encapsulating hydrogel will minimize gliosis and brain tissue damage and (2) to determine whether the combination of electrode movement and incorporation of biochemical's such as NGF within hydrogel coatings will promote better neural connectivity and improved signal quality. The effect of hydrogel coated microelectrodes on brain tissue will be characterized with a rodent model under chronic conditions using histological, electrical, and mechanical methods to test for reduction of neuroinflammation. Using force displacement data for various coated microelectrodes, we will generate a finite element based hyperelastic model of brain tissue under chronic conditions. Additionally, we will characterize the synergistic use of electrode movement and nerve growth factor (NGF) incorporated in hydrogels under chronic conditions using electrophysiological and histological characterization. Successful outcomes of this proposal will entail development of novel strategies for long-term implantation of neural prosthetic devices and better understanding of the impact of microelectrodes on the brain material properties under chronic conditions.