Development and Evaluation of Biodegradable Neural Probes

描述（由申请人提供）：我们建议开发新型可生物降解探针材料，以增强用于神经假体和神经科学的微电极的记录和刺激能力。采用微电极的神经假体和功能性电刺激系统在治疗神经退行性疾病方面的应用不断改进和扩大，同时也为基础神经科学提供了工具。它们现在和未来的应用包括脑机接口、视觉和听觉假体、认知假体（海马）、周围神经假体和深部脑刺激。大多数用于记录和/或刺激微电极系统的结构材料，如硅、金属和陶瓷，都是刚性的。临床应用微电极系统发展的一个主要障碍是它们在长期使用过程中容易失效。研究表明，记录和刺激能力的丧失或恶化可能是由于微电极周围的慢性炎症组织反应，以及由于探针和组织之间的微运动而导致的组织中的局部剪切力和应变导致的。尽管人们已经研究了柔软和灵活的聚合物，但它们的灵活性使得插入大脑目标变得困难。

DESCRIPTION (provided by applicant): We propose to develop novel biodegradable probe materials for enhancing recording and stimulation capabilities of microelectrodes used in neural prostheses and neuroscience. Neural prostheses and functional electrical stimulation systems employing microelectrodes continue to improve and expand their applications in treating neural-degenerative diseases as well as providing tools for basic neuroscience. Their present and future applications include brain-machine interfaces, visual and auditory prostheses, cognitive prosthesis (hippocampus), peripheral nerve prostheses, and deep-brain stimulation. The majority of structural materials used in the recording and/or stimulating microelectrode systems, such as silicon, metals, and ceramics, have been rigid. A main hurdle in the development of the microelectrode system for clinical applications has been their proneness to failure during long-term use. Studies have suggested that loss or deterioration of recording and stimulation capabilities may be due to chronic inflammatory tissue responses around the microelectrode sites, and that local shear forces and strain in the tissue due to micromotion between the probes and the tissue contribute to this. Although soft and flexible polymers have been investigated, their flexibility makes insertion into brain targets difficult. We propose to develop probes with transient mechanical properties that will provide high mechanical stiffness during insertion and gradually degrades over time, leaving the non-degrading flexible polymer probe for long-term use. Our main goal is to develop a novel biodegradable neural probe made of polymer-ceramic composites which allow for control of degradation rate as well as provides mechanical reinforcement. Composition and thickness of the composites will be optimized through acute insertion experiment into animals' brains and by soak-test, and their biocompatibility will be evaluated in-vivo. An underlying hypothesis in this design- or technology-driven project is that these biodegradable probes will result in less chronic inflammatory responses than will rigid probes, which in turn, will result in improved long-term functionality. PUBLIC HEALTH RELEVANCE: Significant health benefits will accrue from increased use of neural prostheses with improved long-term functionality. Their clinical applications include rehabilitation following spinal cord injury or stroke, and sensory deficits such as profound hearing loss, as well as treatments of neurodegenerative diseases, such as Parkinson's disease, epilepsy, and depression. The devices described in this application will also advance knowledge in basic and applied neuroscience.