Biomimetic Surface for Neural Implants

用于神经植入的仿生表面

• 批准号: 8846680
• 负责人: XINYAN Tracy CUI
• 金额: $ 60.32万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8846680
• 关键词: Acute; Address; Animals; Attenuated; Autopsy; Binding; Biochemical; Biocompatible Materials; Biological; Biomimetics; Blood Vessels; Brain; Cell Adhesion Molecules; Characteristics; Chronic; Cicatrix; Clinical; Clinical effectiveness; Cochlear Implants; Coupled; Custom; Deep Brain Stimulation; Development; Devices; Dyes; Electrodes; Epilepsy; Extravasation; Failure; Floor; Goals; Growth Inhibitors; Health; Histology; Human; Image; Immunohistochemistry; Implant; Inflammation; Knowledge; Lead; Life; Light; Link; Longevity; Macaca mulatta; Mental Depression; Microarray Analysis; Microelectrodes; Microglia; Microscopy; Modeling; Modification; Molecular; Morphology; Motor Cortex; Movement; Mus; Names; Nerve Degeneration; Neural Cell Adhesion Molecule L1; Neurites; Neurons; Noise; Ocular Prosthesis; Parkinson Disease; Performance; Primates; Process; Rattus; Reaction; Research; Signal Transduction; Speed; Stem cell transplant; Surface; Technology; Testing; Therapeutic; Time; Tissues; Transgenic Animals; Translating; Transplantation; Visual Cortex; Work; base; brain machine interface; brain tissue; calcium indicator; clinical application; density; design; electric impedance; expiration; functional restoration; implantable device; improved; in vivo; mind control; molecular dynamics; nervous system disorder; neural growth; neuronal growth; novel; novel strategies; promoter; relating to nervous system; repaired; response; scaffold; success; surface coating; tool; two-photon

DESCRIPTION (provided by applicant): R01:Biomimetic Surface for Neural Implant PI: Tracy Cui Implantable microelectrode arrays for neural recording and stimulation have demonstrated tremendous research and clinical potential. Studies of brain tissue response to neural electrode arrays have revealed localized microglia activation, followed by astrocytic scarring and neural degeneration. These reactions are thought to contribute to the low yield and chronic failure of neural recording, although direct links have not been soundly established. Past studies characterizing the CNS response to implants have used postmortem histology at discrete time points. This approach suffers from a large degree of variability and fails to capture the dynamic molecular, cellular and vascular changes of the host. To address this issue, we have developed an experimental set-up to directly image the electrode-tissue interface in live animals using 2-photon microscopy in conjunction with electrical recording. Our previous work indicates that by coating the surface of neural probes with neural adhesion molecules, neuronal density around the device can be promoted while glial reaction attenuated. Meanwhile, neural recording quality is drastically improved. We hypothesize that promoting neuronal growth and health, and/or inhibiting microglia activation will lead to recording improvement. The specific objectives of thi project are to investigate the biological mechanisms of the coating's effect on recording and to evaluate the clinical potential of biomimetic coating in a brain machine interface (BMI) model. First, the acute neuronal and microglia responses to coated probes will be characterized in transgenic animals using two photon imaging and electrical recording for two weeks. Real time tissue characteristics (such as neuronal and neurite density, microglia density and morphology, vasculature change and BBB leakage) will be correlated to recording metrics(such as unit yield, SNR, amplitude of signal and noise as well as impedance). Several biomolecules that promote or inhibit neuronal growth or microglia activation will be immobilized on the Blackrock arrays to test our hypothesis. Secondly, the long-term benefit of the coatings on recording will be determine by testing the optimum coating conditions in rats for 6 months. Explants will be taken monthly to examine the coating longevity, while immunohistochemistry and microarray analysis of the tissue at the interface will be performed to characterize the cellular and molecular change over time. Thirdly, to assess the potential of biomimetic coating for clinical application, coated electrodes will be tested in rhesus monkeys in a brain-machine-interface (BMI) model. Recording metrics such as SNR, signal amplitude, unit yield and stability will be quantified over 2 years and compared to uncoated arrays. A novel functional metric will be developed to assess functionality of the recorded signals. BMI performance will be evaluated based on speed and accuracy. This proposal combines the cutting edge real-time imaging, effective biomaterial strategies and state of the art brain machine interface technology to understand the interactions between neural implants and host tissue. The findings will guide the development of seamless neural interface devices for BMI, visual and auditory prosthesis, deep brain stimulation for Parkinson's disease, depression and epilepsy, to name a few. The knowledge will also benefit other brain implants from biochemical sensing and therapeutic delivery to scaffold and stem cell transplant for treating neurological disorders.

描述（申请人提供）：R01：用于神经植入的仿生表面PI: Tracy Cui用于神经记录和刺激的植入式微电极阵列显示出巨大的研究和临床潜力。大脑组织对神经电极阵列的反应研究揭示了局部小胶质细胞激活，随后是星形细胞瘢痕和神经变性。这些反应被认为是导致低产量和慢性神经记录失败的原因，尽管直接联系尚未完全建立。过去的研究描述了中枢神经系统对植入物的反应，使用的是离散时间点的死后组织学。这种方法存在很大程度的可变性，无法捕捉宿主的动态分子、细胞和血管变化。为了解决这个问题，我们开发了一种实验装置，使用双光子显微镜结合电记录直接对活体动物的电极-组织界面进行成像。我们之前的工作表明，通过在神经探针表面涂覆神经粘附分子，可以提高装置周围的神经元密度，同时减弱神经胶质反应。同时，神经记录的质量得到了极大的提高。我们假设促进神经元的生长和健康，和/或抑制小胶质细胞的激活将导致记录的改善。该项目的具体目标是研究涂层对记录效果的生物学机制，并评估仿生涂层在脑机接口（BMI）模型中的临床潜力。首先，将在转基因动物中使用两周的双光子成像和电记录来表征对涂层探针的急性神经元和小胶质细胞反应。实时组织特征（如神经元和神经突密度、小胶质细胞密度和形态、脉管系统变化和血脑屏障泄漏）将与记录指标（如单产率、信噪比、信号和噪声幅度以及阻抗）相关联。一些促进或抑制神经元生长或小胶质细胞激活的生物分子将被固定在贝莱德阵列上，以测试我们的假设。其次，通过在大鼠身上测试6个月的最佳涂敷条件，来确定涂敷对录音的长期效益。每个月取一次外植体来检查涂层的寿命，同时对界面处的组织进行免疫组织化学和微阵列分析，以表征细胞和分子随时间的变化。再次，评估仿生涂层的临床应用潜力，进行涂层