Nanoelectronics to study exosome circuitry and their role in neuroregeneration

项目摘要 胚胎发育、再生和组织稳态中重要的信号网络之一是 内源性生物电电场可以促进神经轴突的再生 损伤和生物电刺激对于诱导外周和中枢神经系统的再生是至关重要的。 然而，允许细胞将生物电信号转化为基因调控信号的转导机制， 网络并通过胞吐途径将它们传递到受体细胞的机制尚未完全了解。的 未来五年MIRA应用的首要目标是了解内源性 电场对通过小细胞外囊泡（EV）的胞吐途径的影响;并利用这一知识 在未来建立一种新的基于EV的治疗方法，以恢复神经系统中神经元的功能和修复。 疾病和伤害。为了解决知识差距，我们的目标是首先电刺激许旺细胞（SC）， 周围神经系统的神经胶质成分，通过开发仿生压电神经网络， 来模拟内源性生物电刺激。提出的生物活性压电纳米纤维将是 由于它们具有高空间分辨率和高表面体积比， 可以促进细胞附着和排列。此外，纤维的压电特性允许细胞自我- 诱导电刺激作为机械生物学的结果，其可以更好地模拟内源性 在三维（3D）微环境中的细胞网络之间的机械转导反馈回路。 我们计划进一步研究从电刺激的SC分泌的EV的作用，作为货物传输 通过RNA和蛋白质的生物电信号的神经元，并研究其功能作用，促进 轴突再生

Project Summary One of the important signaling networks in embryonic development, regeneration, and homeostasis of tissue is the endogenous bioelectricity. It has been observed that electric fields can promote axonal regrowth in nerve injury and bioelectric stimuli can be crucial to induce regeneration in peripheral and central nervous systems. However, the transduction mechanisms that allow cells to convert bioelectric signals into gene regulatory networks and transmit them to recipient cells via exocytosis pathways has not been fully understood. The overarching goals of this MIRA application for the next five years will be to understand the effect of endogenous electric fields on exocytosis pathway through the small extracellular vesicles (EVs); and to use this knowledge in the future to establish a new EV-based therapeutic to restore function and repair of neurons in neurological disorders and injuries. To address the knowledge gaps, we aim to first electrically stimulate Schwann cells (SCs), the glial component of peripheral nervous system, by developing a biomimetic piezoelectric nanofiber networks to mimic the endogenous bioelectric stimuli. The proposed bioactive piezoelectric nanofibers will be advantageous over current technologies since they have high spatial resolution and high surface to volume ratio that can promote cells attachment and alignment. Also, the piezoelectric properties of fibers allow cells to self- induce electrical stimulation as a result of mechanobiology which can better mimic the endogenous mechanotransduction feedback loop between cellular networks in a three-dimensional (3D) microenvironment. We further plan to investigate the role of EVs secreted from electrically stimulated SCs, as cargos to transmit the bioelectric signals by means of RNAs and proteins to neurons and to study their functional role in promoting the axonal regeneration.