Soft, conformal wireless optoelectronic systems for the long-term neuromodulation of bladder function

 描述(申请人提供)：膀胱痛和功能障碍是美国数百万间质性膀胱炎/膀胱痛综合征、膀胱过度活动和神经源性膀胱患者严重虚弱的根源。目前对这些疾病的治疗是无效的，并且没有解决潜在的病理问题。发展改进的治疗方法的一个重要障碍是对膀胱控制机制的了解不足。进展将关键取决于神经接口新技术的发展。特别是，光遗传学方法与用于神经记录和电刺激的新型无线光电子系统和电子硬件的组合将提供一套独特的工具，以增强对周围器官控制的洞察。此外，实时测量神经炎症和可编程地在神经接口提供局部抗炎剂的能力不仅将允许强大、高性能的慢性集成，而且还将进一步了解其他应用中神经设备接口的维护。在这个方案中，我们开发了一套柔软的、完全可植入的微型设备，具有先进的设计特征，专门配置为最大限度地减少和减轻炎症，基本上与目标神经永久整合。在目标1中，我们建议将光遗传技术与完全可植入的无线系统相结合，以抑制支配膀胱的外周神经元。在目标2中，我们建议将超薄、柔性电极技术和新型神经炎性监测器集成到膀胱周围神经的无线控制中。在目标3中，我们集成了一个完全可植入、无线可编程的微流体平台，用于慢性神经界面的闭环维护。我们的协作团队广泛成功地将技术融合到统一的多模式设备中，并随后将其应用于神经元亚群的机制研究。由这些目标产生的技术将处于研究末端器官功能控制机制的最佳位置，并以一种微创的方式做到这一点。

 DESCRIPTION (provided by applicant): Bladder pain and dysfunction are sources of profound debilitation for millions of people in the United States with interstitial cystitis/bladde pain syndrome, overactive bladder, and neurogenic bladder. Current treatments for these disorders are ineffective and do not address the underlying pathology. A substantial barrier to the development of improved therapeutics is an insufficient understanding of mechanisms by which the bladder is controlled. Progress will depend critically on the development of new technologies in neural interfaces. In particular, a combination of optogenetic approaches along with new, wireless optoelectronic systems and electronic hardware for nerve recording and electrical stimulation will provide a unique set of tools for enhanced insights into peripheral organ control. Additionally, the ability to measure, in real-time, neural inflammation and to programmably deliver local anti-inflammatory agents at the neural interface will not only allow robust, high performance chronic integration, but also further the understanding of maintenance at nerve- device interfaces in other applications. In this proposal, we develop a suite of soft, fully-implantable microscale devices with advanced design features specifically configured to minimize and mitigate inflammation for essentially permanent integration with the targeted nerves. In Aim 1, we propose to integrate optogenetic technologies with fully-implantable wireless systems for inhibition of peripheral neurons innervating the bladder. In Aim 2, we propose to integrate ultra-thin, flexible electrode technology and novel neuroinflammatory monitors to the wireless control of bladder peripheral nerves. In Aim 3, we integrate a fully-implantable, wirelessly programmable microfluidic platform for closed-loop maintenance of the chronic nerve interface. Our collaborative team has extensive success merging technologies into unified multi-modal devices and subsequently applying them to the mechanistic study of neuronal subpopulations. The technology produced by these aims will be optimally positioned to study mechanisms of control of end-organ function, and to do so in a way that is minimally invasive.