CAREER: Multifunctional Soft Neural Probes for Elucidating Spinal Cord Injury Pathophysiology

脊髓损伤（SCI）是美国瘫痪的主要原因之一。超过140万人患有与重度神经损伤相关的残疾，这导致参与率较低，并产生了巨大的个人和社会成本。目前大多数脊髓系统的神经技术依赖于直接向组织注入电流。然而，这种电方法不足以找出哪种类型的细胞有助于损伤恢复，因为电影响某些区域的所有神经元而没有选择。为了克服这些限制，这个CAREER项目寻求开发一种新的软设备技术，利用光、电、药物和病毒基因载体来研究脊髓系统。这种神经技术的发展需要来自多个学科的知识。因此，该项目为对STEM有广泛兴趣的学生提供了各种教育机会。研究者的目标是在马萨诸塞大学阿默斯特分校的工程和神经科学部门开展一个跨学科的神经工程项目。该项目将通过开发针对残疾学生的课程、互动在线中心和一系列以K-12学生为中心的以神经技术为主题的拓展活动，将研究和教育活动结合起来。研究者的长期职业目标是建立研究神经系统的工程平台方法，并最终开发神经系统功能障碍的治疗方法。利用材料工程和神经科学的知识，研究者假设一种新的多功能软神经探针技术的发展可以促进对SCI神经病理生理的整体理解。研究目标将通过以下四个具体任务来实现：(1)利用聚合物工程方法开发一种新的多功能软神经探针技术。水凝胶材料的光学和机械性能可以通过调整其底层的纳米和微尺度结构来微调。优化水凝胶组件的材料特性，使探针能够将光传输到脊髓靶区进行光神经调制和记录，并适应脊髓组织在体内的运动。(2)在体内测试软神经探针的多功能性和长期生存能力。软神经探针的设计允许光学刺激和光度记录、电记录、药物输注和病毒在小型化设备内传递，而不限制自然运动。(3)利用软神经探针研究脊髓运动回路，采用一系列运动行为测试评估脊髓损伤功能恢复。(4)应用软神经探针进行遗传和药理干预，促进脊髓损伤小鼠模型功能恢复。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Spinal cord injury (SCI) is one of the leading causes of paralysis in the US. Over 1.4 million people live with SCI-related disabilities, which leads to lower participation and gives rise to substantial individual and societal costs. Most of the current neurotechnology for the spinal cord system relies on directly injecting electricity into the tissues. However, this type of electrical approach is inadequate to find out which type of cells contributes to injury recovery because electricity affects all the neurons in certain areas without selection. To overcome such limitations, this CAREER project seeks to develop a new soft device technology to study the spinal cord system using light, electricity, drug, and virus gene carriers. The development of this neurotechnology requires knowledge from multiple disciplines. Therefore, this project opens various educational opportunities for students with a broad interest in STEM. The investigator aims to launch an interdisciplinary neuroengineering program across the engineering and neuroscience departments at UMass Amherst. This program will combine research and educational activities through the development of a curriculum inclusively designed for students with disabilities, an interactive online hub, and a series of student-centered neurotechnology-themed outreach activities for K-12 students. The investigator’s long-term career goal is to establish engineering platform methodologies to investigate the nervous system and ultimately develop therapeutics for nervous system dysfunction. Using the knowledge of materials engineering and neuroscience, the investigator hypothesizes that the development of a new multifunctional soft neural probe technology can advance a holistic understanding of neural pathophysiology in SCI. The research goals will be accomplished through four specific tasks: (1) Developing a new multifunctional soft neural probe technology with polymer engineering approaches. The optical and mechanical properties of hydrogel materials can be fine-tuned by tweaking their underlying nano- and micro-scale structures. Optimizing the material properties of the hydrogel component allows the probe to transmit light to the spinal cord target areas for optical neural modulation and recording, and to adapt to the spinal cord tissue movement in vivo. (2) Testing the multifunctionality and long-term viability of the soft neural probes in vivo. The soft neural probes are designed to allow optical stimulation and photometric recording, electrical recording, drug infusion, and virus delivery within miniaturized devices without constraining natural movement.(3) Investigating spinal locomotor circuits with soft neural probes using a series of locomotor behavioral tests to assess SCI functional recovery. (4) Applying the soft neural probes for genetic and pharmacological interventions to promote functional recovery in SCI mouse models.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.