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

基于细胞外基质的微机械神经电极的体内评估

• 批准号: 9092465
• 负责人: MARK G. ALLEN
• 金额: $ 24.15万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9092465
• 关键词: Adhesions; Amputees; Area; Astrocytes; Attenuated; Behavior; Binding; Biocompatible Materials; Biological; Biological Process; Biomimetics; Brain; Cell Survival; Chronic; Collagen; Collagen Type IV; Cues; Development; Device Designs; Devices; Dimensions; Discipline; Electrical Engineering; Electrodes; Electronics; Electrophysiology (science); Ensure; Evaluation; Exhibits; Extracellular Matrix; Extracellular Matrix Proteins; Faculty; Fibronectins; Geometry; Implant; In Vitro; Inflammatory; Inflammatory Response; Injury; Investigation; Laminin; Limb structure; Long-Term Effects; Mechanics; Methods; Microelectrodes; Microfabrication; Modeling; Nanotechnology; Natural Products; Natural regeneration; Neurons; Neurophysiology - biologic function; Performance; Persons; Process; Property; Prosthesis; Proteins; Protocols documentation; Reaction; Research; Resolution; Series; Site; Supervision; System; Techniques; Technology; Time; Tissues; Work; base; biological systems; body system; brain machine interface; density; design; discrete time; experience; implantation; improved; in vivo; miniaturize; nanofabrication; neurotransmission; next generation; programs; public health relevance; relating to nervous system; response; spatiotemporal; tool

 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.

 描述（由申请人提供）：神经微电极（NE）是一种与体内神经系统进行电连接的强大工具，可以对皮质系统以及脑机接口（BMI）进行科学研究。 然而，NE 面临的一个重大挑战是保持长期功能，因为这些神经接口装置的植入和长期存在会引发一系列生物过程，最终将 NE 与神经系统隔离。 研究发现，来自天然脑细胞外基质（ECM）的生物活性材料可以促进神经向内生长和再生，并支持一系列稳定神经功能的反应。 最近，已经开发出微加工技术，能够实现主要由 ECM 材料组成的电极，其具有足够的复杂性，能够插入体内皮层神经系统并进行记录。 我们假设，由于其生物活性和机械相似特性，与传统的无机对应物相比，这种基于 ECM 的 NE 在慢性植入场景中将表现出更长的功能持续时间。 我们建议开发基于 ECM 的微创 NE，初步了解基于 ECM 的 NE 的体内行为，并评估基于 ECM 的 NE 与无机对照相比的长期耐久性。 我们相信，了解 ECM-NE 的电气、机械和生物性能将使神经接口设备能够在体内保持持续可靠的性能。 拟议的项目位于神经工程、电气工程和微加工技术学科的交叉点。 该项目将主要由两名博士后在三名教员的监督下进行——其中一名在神经工程和神经接口材料方面拥有丰富的经验；另一名在神经工程和神经接口材料方面拥有丰富的经验。一位在神经系统慢性记录方面拥有丰富经验的人；一位在微加工技术（尤其是应用于生物系统和应用）方面拥有丰富经验的人。 我们预计该计划将持续两年，并为以下领域的其他工作提供肥沃的土壤：（1）基于蛋白质的大脑接口； (2)微纳米加工技术。