Improving chronic neural recording performance through biomaterial strategies

描述（由申请人提供）：皮质植入物具有巨大的研究和治疗重要性。人们正在开发人造装置，将其放置在大脑中以恢复功能、治疗神经系统疾病或监测生理环境。在这些应用中使用的设备面临的一个共同问题是缺乏脑组织生物相容性。在这个项目的范围内，注意力集中在脑机接口研究中使用的神经记录电极阵列的发展，其中从这些电极记录的运动信号可以用来控制外部机器，这项技术有可能恢复瘫痪者的运动。然而，目前这些装置的慢性性能不理想，极大地阻碍了它们的临床转化。植入的电极会引起进行性脑组织反应，包括神经元丢失和炎性神经胶质瘤，这可能导致信号丢失。我们假设促进植入物周围的神经元健康和减少慢性炎症可能提高慢性记录的质量、可靠性和寿命。为了验证这些假设，我们开发了两种独特的生物材料策略。一种是将脑源性生物分子表面固定在植入物上，以一种侵入性较小的方式为宿主组织提供生物活性位点。另一种策略是电控药物释放系统，可以直接从电极表面释放抗炎药物来调节炎症组织反应。首先，我们将分别描述这两种方法对改变植入电极周围组织反应的影响，并确定促进神经元健康和减少炎症对慢性记录性能的影响程度。评估完成后，将系统地结合表面修饰和药物控释两种方法，研究在改善组织-种植体界面和慢性记录方面是否存在协同作用。我们的具体目标是：1)确定促进神经元存活和健康对慢性记录质量、寿命和可靠性的影响。2)探讨炎症对慢性记录质量、寿命和可靠性的影响。3)评价表面修饰与药物释放联合处理对慢性记录质量、寿命和可靠性的影响。如上所示，本课题既有基础研究目标，也有应用目标。长期记录改进是我们应用程序驱动的直接目标。然而，对脑组织对植入物的反应以及不同的生物材料策略如何调节这些反应的基本理解对于所有类型的神经植入物至关重要，包括神经记录设备、刺激器、中枢神经系统药物输送系统和生化传感器。公共卫生相关性：正在开发人造装置，将其放置在大脑中以恢复功能和治疗神经系统疾病。该项目的目标是研究可以采取的新方法，使植入设备对大脑更友好，从而获得更好的性能、寿命和可靠性。

DESCRIPTION (provided by applicant): Cortical implants possess tremendous research and therapeutic importance. Man-made devices are being developed to be placed in the brain to restore function, treat neurological disease or monitor the physiological environment. A common problem faced by devices used in these applications is the lack of brain tissue biocompatibility. Within the scope of this project, attention is focused on the development of neural recording electrode arrays used in brain-machine interface studies, in which motor signals recorded from these electrodes can be used to control an external machine, a technology that can potentially restore movement to the paralyzed. However, the current unsatisfactory chronic performance of these devices has greatly hindered their clinical translation. The implanted electrodes cause progressive brain tissue responses including neuronal loss and inflammatory gliosis, which may lead to signal loss. We hypothesize that promoting neuronal health around the implant and reducing chronic inflammation may improve the quality, reliability and longevity of chronic recording. To test these hypotheses we developed two unique biomaterial strategies. One is surface immobilization of brain-derived biomolecules on the implant to provide bioactive sites for host tissue to interact with in a less invasive manner. The other strategy is an electrically controlled drug release system that can release anti-inflammatory drugs directly from the electrode surface to modulate the inflammatory tissue response. First we will respectively characterize the effect of these two approaches on modifying the tissue responses around the implanted electrodes, and determine to what degree promoted neuronal health and reduced inflammation influence the chronic recording performance. After the assessment is completed, the surface modification and controlled drug release approaches will be systematically combined to investigate whether there is a synergistic effect on the improvement of tissue- implant interface and chronic recording. Our specific aims are 1) To determine the effect of promoted neuronal survival and health on chronic recording quality, longevity and reliability. 2) To investigate the role of inflammation on chronic recording quality, longevity and reliability. 3) To evaluate the effect of combined treatment of surface modification and drug release on chronic recording quality, longevity and reliability. As shown above, the proposed project has both basic research and applied objectives. Chronic recording improvement is our immediate application-driven goal. However, the fundamental understanding of brain tissue response to implants and how different biomaterial strategies may modulate these responses are critically important for all types of neural implants, including neural recording devices, stimulators, CNS drug delivery systems and biochemical sensors. PUBLIC HEALTH RELEVANCE: Man-made devices are being developed to be placed in the brain to restore function and treat neurological disease. The goal of this project is to investigate the novel approaches that can be taken to make the implanted device more brain friendly and thereby obtain improved performance longevity and reliability.