Development and Evaluation of Biodegradable Neural Probes

描述(申请人提供)：我们建议开发新的可生物降解的探针材料，以增强神经假体和神经科学中使用的微电极的记录和刺激能力。使用微电极的神经假体和功能性电刺激系统继续改进和扩大其在治疗神经退行性疾病方面的应用，并为基础神经科学提供工具。它们目前和未来的应用包括脑机接口、视觉和听觉假体、认知假体(海马体)、周围神经假体和脑深部刺激。在记录和/或激励微电极系统中使用的大多数结构材料，例如硅、金属和陶瓷，都是刚性的。开发临床应用的微电极系统的一个主要障碍是它们在长期使用过程中容易失败。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，以及探针和组织之间的微小运动导致的组织中的局部剪切力和应变。尽管人们已经研究了柔软和灵活的聚合物，但它们的灵活性使插入脑靶点变得困难。 我们建议开发具有瞬时机械性能的探头，这些探头在插入过程中提供高机械硬度，并随着时间的推移逐渐退化，从而使不可降解的柔性聚合物探头长期使用。我们的主要目标是开发一种新型的可生物降解的神经探头，它由聚合物-陶瓷复合材料制成，既可以控制降解速度，又可以提供机械增强。复合材料的组成和厚度将通过动物脑内急性植入实验和浸泡实验进行优化，并将在体内进行生物相容性评价。在这个设计或技术驱动的项目中，一个潜在的假设是，这些可生物降解的探头将比硬质探头产生较少的慢性炎症反应，这反过来将导致改善长期功能。 与公共健康相关：增加神经假体的使用将带来显著的健康益处，并改善长期功能。它们的临床应用包括脊髓损伤或中风后的康复，以及严重听力损失等感觉障碍，以及帕金森病、癫痫和抑郁症等神经退行性疾病的治疗。本申请中描述的设备还将提高基础神经科学和应用神经科学的知识。

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.