Novel Bioactive Coatings for Chronically Implanted MEMS based Moveable Microelect

用于长期植入 MEMS 的可移动微电子的新型生物活性涂层

• 批准号: 8127581
• 负责人: Arati Sridharan
• 金额: $ 5.15万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2014-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8127581
• 关键词: Address; Alzheimer' s Disease; Anti-Inflammatory Agents; Anti-inflammatory; Astrocytes; Biochemical; Biological; Biomechanics; Brain; Chronic; Cicatrix; Data; Deterioration; Development; Devices; Diffusion; Disease; Electrodes; Elements; Encapsulated; Glial Fibrillary Acidic Protein; Gliosis; Goals; Hydrogels; Implant; Inflammation; Inflammatory; Injury; Lead; Life; Mechanics; Methods; Microelectrodes; Modeling; Movement; Nerve Growth Factors; Neurodegenerative Disorders; Neurons; Outcome; Paralysed; Parkinson Disease; Penetration; Polymers; Process; Property; Prosthesis; Rattus; Research Proposals; Rodent Model; Signal Transduction; Simulate; Stress; Stroke; Surface Properties; Symptoms; Testing; Time; Tissues; Trauma; Traumatic Brain Injury; base; brain tissue; crosslink; density; electric impedance; implantation; improved; in vivo; innovation; models and simulation; neural prosthesis; neuroinflammation; novel; novel strategies; prevent; relating to nervous system; shear stress; simulation; stem

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. PUBLIC HEALTH RELEVANCE: The proposed study to develop novel bioactive coatings will help to incorporate life-saving neural implants over the long term. Successful outcomes of this proposal will lead to novel approaches to develop methods to incorporate neural prosthetics and other biomedical devices with reduced biological rejection and increased device functionality. Chronic implantation of neural prosthetics will help in the treatment of debilitating diseases like Alzheimer's disease, Parkinson's disease, and stroke.

描述（由申请人提供）：皮质神经假体是一种很有前途的方法，可以缓解各种神经退行性疾病的症状，从阿尔茨海默病和帕金森病到瘫痪性脑外伤，如中风。这些装置中的主要障碍是在慢性条件下信号质量的缓慢恶化，这主要是由于（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）神经元在神经界面处与电极断开。本研究提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提高信号质量。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促进神经连接。主要焦点是通过生物化学释放来抑制炎症。在这里，我们建议采取更进一步的措施，并试图通过调整封装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并最大限度地减少炎症。我们将测试的假设，多晶硅微电极封装在水凝胶涂层具有类似的脑组织的粘弹性将导致对组织的应变较小，从而减少神经炎症和改善信号质量在慢性条件下。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性神经界面。为了实现这一目标，具体的目的是（1）确定包封水凝胶的交联密度和相关刚度是否将使神经胶质增生和脑组织损伤最小化，以及（2）确定电极移动和生物化学物质如NGF掺入水凝胶涂层内的组合是否将促进更好的神经连接和改善的信号质量。将在慢性条件下使用啮齿动物模型，使用组织学、电学和机械方法表征水凝胶涂层微电极对脑组织的影响，以测试神经炎症的减少。使用各种涂层微电极的力位移数据，我们将生成基于有限元的慢性条件下的脑组织超弹性模型。此外，我们将使用电生理学和组织学表征的协同使用的电极运动和神经生长因子（NGF）纳入水凝胶在慢性条件下。这一建议的成功结果将需要开发新的策略，用于长期植入神经假体装置，并更好地了解微电极对慢性条件下大脑材料特性的影响。 公共卫生关系：拟议的开发新型生物活性涂层的研究将有助于长期纳入拯救生命的神经植入物。这一建议的成功结果将导致新的方法来开发方法，将神经假体和其他生物医学设备与减少生物排斥和增加设备功能。神经假体的长期植入将有助于治疗使人衰弱的疾病，如阿尔茨海默病、帕金森病和中风。