Multifunctional Polymer Neuronal Probes

描述（由申请人提供）：监测和控制神经元群的能力对公共卫生有着深远的影响，从对认知障碍的基本理解到对瘫痪肢体的主动控制。最先进的神经元探针是基于坚硬的陶瓷和金属材料，这些材料与软脑组织的长期生物相容性差，电记录性能适中。这些缺点妨碍了研究或修改清醒行为动物的神经基础所必需的长期测量的可能性。这项探索性/发展奖（R21）申请的愿景是开发基于新兴聚合物材料和最先进制造技术的神经探针，展示长期生物相容性。这项工作的具体目标是开发一种慢性神经元探针，使用具有最佳电记录性能的微线封装在定制的生物相容性聚合物传递结构中。聚合物鞘的多功能特性，如形状记忆能力和生物降解性，将用于探索先进的探针设计概念，如自插入和消失插入系绳，这两者都应该提高长期生物相容性，促进高保真慢性神经元测量。提出的聚合物神经元探针应该对探针技术产生广泛的影响，为未来的组织工程探针提供了一个平台，可以用于细胞支架和治疗药物的控制释放。提出的工作的两个具体目标旨在消除聚合物神经元探针发展的最重要障碍；小规模制造，机械可插入性和生物相容性评估。在Aim 1中，双光子立体光刻将用于制造各种设计的金微线封装聚合物探针。在目标2中，将使用体外纳米压痕和小鼠嗅球体内插入测试来评估探针的局部和整体力学特性。利用小鼠嗅球模型评估探针的短期和长期生物相容性。还将使用类似的体外和体内方法对探针进行多功能自我部署和生物降解研究。

DESCRIPTION (provided by applicant): The ability to monitor and control neuronal ensembles has far reaching impact on public health ranging from a fundamental understanding of cognitive disabilities to active control of paralyzed limbs. State-of-the-art neuronal probes are based on stiff ceramic and metallic materials that demonstrate poor long-term biocompatibility with soft brain tissue and moderate electrical recording properties. These shortcomings circumvent the possibility of chronic measurements necessary for studying or modifying the neural basis of behavior in awake-behaving animals. The vision of this Exploratory/Developmental Award (R21) application is to develop neuronal probes demonstrating long-term biocompatibility based on emerging polymer materials and state-of-the-art fabrication technologies. The specific objective of the work is to develop a chronic neuronal probe using microwires with optimal electrical recording properties encapsulated within a tailored biocompatible polymer delivery structure. Multifunctional properties of the polymer sheath, e.g. shape memory capacity and biodegradability, will be used to explore advanced probe design concepts such as self-insertion and vanishing insertion tethers, both of which should improve long-term biocompatibility and facilitate high-fidelity chronic neuronal measurements. The proposed polymer neuronal probes should have broad impact on probe technology by providing a platform for future tissue engineered probes capable of cell scaffolding and controlled release of therapeutic drugs. The two specific aims of the proposed work are designed to eliminate the most significant barriers to the development of polymer neuronal probes; small-scale fabrication, mechanical insertability, and biocompatibility assessment. In Aim 1, two-photon stereolithography will be used to fabricate gold microwire encapsulated polymer probes with various designs. In Aim 2, the local and global mechanical properties of the probes will be assessed using in-vitro nanoindentation and in-vivo insertion tests into a mouse olfactory bulb. Short and long term biocompatibility of the probes will be assessed using the mouse olfactory bulb model. Multifunctional self-deployment and biodegradation studies will also be conducted on the probes using similar in-vitro and in-vivo approaches.