CAREER: A Robust, Chronic Neural Prosthesis Using High-Capacity Graphene Electrodes and Biodegradable Silicon Support

用于短期（急性）应用的神经植入物在研究环境和猴子实验中取得了重大成功。然而，由于缺乏一种强大的、慢性的植入式装置，神经植入物的临床成功有限。缺乏慢性植入技术是医疗保健中的一个重大问题，因为大多数神经紊乱和疾病需要长期治疗，包括失明、耳聋、癫痫、帕金森病和脊髓损伤。PI的长期目标是研究一种强大的、高性能的慢性植入式系统，该系统集成了微制造和生物材料，以提高生活质量，并用于微/纳米和分子尺度的神经网络研究。为了实现这一目标，本CAREER提案的研究目标是利用神经植入材料的创新进展，包括(i)阐明石墨烯（一种新型碳材料）的电荷注入机制；在生理环境和（ii）理解和操作脑组织和植入式电极之间的界面，使用多孔硅骨干支撑，缓慢而安全地生物降解到脑组织中，同时随时间释放抗炎药物（地塞米松）。PI提议发起并领导一项实质性的研究工作：-将石墨烯应用于神经刺激和记录的电极材料。-将生物相容性可生物降解的多孔硅应用于神经假体界面。-将石墨烯和多孔硅集成到神经植入物中，优化机械性能、生物相容性和给药效率。-研究神经植入物的体内功能测试和生物相容性研究。本研究将有助于推进神经系统与不同电化学、力学和材料性质的生物材料之间相互作用的基础知识。了解其基本机制对于开发神经义肢来帮助残疾人是非常重要的。如果成功，这项研究将使我们能够研究和了解大脑中单个神经元的活动，因为我们的方法不仅消除了微运动引起的噪音，而且提供了可靠的、高分辨率的、长期的神经元刺激和记录。该研究在神经科学、药物传递、生物电子学、生物传感器和安全等领域具有广泛的应用。神经植入物的实时传感和治疗可用于治疗多种神经系统疾病。仅在美国，就有超过20万名完全或部分瘫痪的患者可能受益于这项技术。照顾这些病人的费用每年远远超过2000亿美元。长期的神经记录可以为假肢设备提供高分辨率的实时信号。这也为神经元疾病提供了可能的治疗方法，如瘫痪、失明、耳聋和帕金森氏症。PI的教育目标是扩大工程中代表性不足的群体的参与，并为学生的专业工程生涯做好准备。PI提出了一项全面的教育和推广计划，包括指导毕业生、本科生和来自代表性不足群体的学生，并将研究成果与MEMS/NEMS和使能技术等课堂教学相结合。拟议的教育计划将通过nsf赞助的SURA和REU计划来完成，以招收代表性不足的本科生和韦恩州立大学（WSU）的残疾学生。PI与底特律科学中心（DSC）合作举办“纳米日”和“纳米夏令营”系列活动，吸引女性和代表性不足的K-12儿童参与纳米技术。PI将在华盛顿州立大学组织年度纳米研讨会/研讨会，向密歇根州东南部的学术界和当地工业广泛传播纳米技术和生物医学研究。

Cheng1055932Neural implants used for short term (acute) applications have had major success in research settings and monkey experiments. However, neural implants have had limited clinical success due to the lack of a robust, chronic implantable device. The lack of chronic implant technology represents a significant problem in healthcare because the majority of neural disorders and diseases require chronic treatment, including blindness, deafness, epilepsy, Parkinson's disease, and spinal cord injury. The PI's long-term goal is to research a robust, high-performance, chronic implantable system that integrates microfabrication and biomaterials for the improvement of quality of life and for the study of neural networks at micro/nano and molecular scales. In pursuit of this goal, the research objective of this CAREER proposal is to use innovative advances in neural implantable materials, including (i) elucidate the mechanism of charge injections of graphene, a novel carbon material, in physiological environments and (ii) understand and manipulate the interface between the brain tissue and implantable electrodes using a porous silicon backbone support that is slowly and safely biodegraded into brain tissue while releasing anti-inflammatory medication (dexamethasone) with time. The PI proposes to initiate and lead a substantial research effort to:- Apply graphene to electrode materials for neural stimulation and recording.- Apply biocompatible biodegradable porous silicon to the interface of neural prostheses.- Integrate graphene and porous silicon into a neural implant and optimize mechanical properties, biocompatibility, and drug delivery efficiency.-Investigate in-vivo functional test and biocompatibility study of the neural implant.Intellectual Merit This proposed research will help advance fundamental knowledge of the interaction between neural system and biomaterials of different electrochemical, mechanical and material properties. Understanding the fundamental mechanism is important in the development of neural prosthesis to aid people with disabilities. If successful, this research will enable us to study and understand the activities of single-neurons in the brain because our method not only eliminates the noises caused by micro-motions but also provides reliable, high-resolution and long-term neuron stimulation and recording. This research has a broad range of applications, such as neuroscience, drug delivery, bioelectronics, biosensor and security.Broader Impact The real-time sensing and treatment by neural implants can be used to treat a variety of neurological maladies. More than 200,000 patients with full or partial paralysis may benefit from this technology in the US alone. The cost of care for these patients is well over $200 billion per year. Long-term neural recording can provide a high-resolution, real-time signal needed for prosthetic devices. This also offers possible treatment of neuron disorders, such as paralysis, blindness, deafness and Parkinson's disease. The PI's educational goals are to broaden the participation of underrepresented groups in engineering and to prepare students for a professional engineering career. The PI proposes a comprehensive education and outreach plan that includes mentoring graduates, undergraduates and students from underrepresented groups, and integrating research results with classroom teaching such as MEMS/NEMS and enabling technologies. The proposed educational plan will be accomplished through NSF-sponsored SURA and REU programs to recruit underrepresented undergraduate students and students with disabilities at Wayne State University (WSU). The PI collaborates with the Detroit Science Center (DSC) in the series of "Nano Days" and "Nano Summer Camp" to engage women and underrepresented K-12 kids with nanotechnology. The PI will organize annual Nano Symposium/workshop at WSU to broadly disseminate nanotechnology and biomedical research to academics and local industry in Southeastern Michigan.