In-vivo Assessment of Extracellular-Matrix-Based Micromachined Neuroelectrodes

 描述（由申请人提供）：神经微电极（内斯）是一种与体内神经系统电连接的强大工具，能够对皮质系统以及脑机接口（BMI）进行科学研究。 然而，内斯的一个重大挑战是保持慢性功能，因为这些神经接口装置的植入和长期存在会诱导一系列生物过程，最终将内斯与神经系统隔离。 来自天然脑细胞外基质（ECM）的生物活性物质被发现可以促进神经生长和再生，并支持一系列稳定神经功能的反应。 最近，已经开发了微制造技术，其使得能够实现主要由ECM材料组成的电极，具有足够的复杂性以使得能够插入到体内皮层神经系统中并从体内皮层神经系统记录。 我们假设，由于它们的生物活性和力学相似性，这种基于ECM的内斯将在慢性植入场景中表现出更长的功能持续时间相比，其传统的无机对应物。 我们建议开发最小损伤的基于ECM的内斯，实现初步了解基于ECM的内斯在体内的行为，并评估基于ECM的内斯与无机对照相比的慢性耐久性。 我们相信，了解ECM-NEs的电气，机械和生物性能将使神经接口设备能够在体内持续和可靠的性能。 该计划位于神经工程，电气工程和微制造技术学科的交叉点。 它将主要由两名博士后在三个教师的监督下进行-一个在神经工程和神经接口材料方面具有重要经验;一个在神经系统慢性记录方面具有重要经验;一个在微制造技术方面具有重要经验，特别是应用于生物系统和应用。 我们预计该计划将持续两年，并为以下领域的额外工作提供肥沃的土壤：（1）基于蛋白质的大脑接口;和（2）微米和纳米纤维技术。

 DESCRIPTION (provided by applicant): Neural microelectrodes (NEs) are a powerful tool for electrically interfacing with neural systems in-vivo, enabling scientific studies of cortical systes as well as brain-machine interfaces (BMI). However, a significant challenge for NEs is to retain chronic function, since the implantation and chronic presence of these neural interface devices can induce a cascade of biological processes that ultimately isolate the NEs from the neural system. Bioactive materials from natural brain extracellular matrix (ECM) are found to promote neural ingrowth and regeneration, and support a series of reactions stabilizing neural function. Recently, microfabrication technologies have been developed that enable the realization of electrodes comprised primarily from ECM materials, with sufficient complexity to enable insertion into and recording from cortical neural systems in-vivo. We hypothesize that due to their bioactivity and mechanosimilar properties, such ECM-based NEs will exhibit longer duration of functionality in chronic implant scenarios compared to their conventional inorganic counterparts. We propose to develop minimal-injury ECM-based NEs, achieve initial understanding of the behavior of ECM-based NEs in vivo, and assessing the chronic durability of ECM-based NEs compared to inorganic controls. We believe that understanding the electrical, mechanical and biological performance of ECM-NEs will enable neural interface devices which are capable of sustained and reliable performance in vivo. The proposed program sits at the intersection of the disciplines of neuroengineering, electrical engineering, and microfabrication technology. It will be carried out primarily by two postdoctoral associates under the supervision of three faculty - one with significant experience in neuroengineering and neural interface materials; one with significant experience in chronic recording from neural systems; and one with significant experience in microfabrication technology, especially as applied to biological systems and applications. We expect this program to last two years and provide fertile ground for additional work in the areas of (1) protein- based interfaces to the brain; and (2) micro- and nanofabrication technology.