Marco/Micro Substrate Stiffness and Effect on Rat Brain Cortex

描述（由申请方提供）：本研究的重点是研究基质硬度在组织对皮质植入物反应中的作用，以便与神经组织形成更持久、更紧密的界面。大脑皮层电极已经在神经科学中显示出巨大的进步，有助于理解大脑的结构和功能。用于恢复神经受损个体的运动功能的应用已经显示出恢复功能的前景。皮质电极无法实现作为可行临床选择的寿命和稳定性。对寿命的限制是在植入物周围形成胶质瘢痕。提出反应是由于两种模式：宏观模式和微观模式。宏观模式是由软神经组织中的硬植入物引起的剪切应力、差动效应。微观模式是一种机械转导机制，其中细胞通路基于基底刚度激活。第一个目标将通过使用可弯曲刚度材料系统来研究细胞微/硬旋转反应，以通过免疫组织化学（IHC）分析细胞反应。第二个目标将通过使用机械动态纳米复合材料来研究宏观/剪切应力的影响，以通过IHC测量组织反应。第三个目的是通过使用纳米复合材料封装的电极经由电生理学评估组织响应。植入物的免疫组织化学和电极的电生理学将提供定量数据来区分材料的性能。拟议的工作旨在融合神经科学和神经工程的观点，合并这些领域，以了解治疗神经疾病和设计未来神经设备至关重要的基本原理。该研究的重点是细胞对植入体刚度的反应，本研究中获得的信息将广泛适用于许多健康领域。材料硬度与干细胞分化、癌症发展、脊髓再生和组织工程等领域有关。增加皮质植入物的寿命也将允许临床功能恢复和神经系统疾病的研究。这项研究将提供第一个全面的研究刚度为基础的组织反应，皮质植入物在体内。

DESCRIPTION (provided by applicant): The focus of this study is to investigate the role of substrate stiffness in the tissue response to cortical implants in order to create a longer-lasting, more intimate interface with neural tissue. Cortical electrodes have already shown great advances in neuroscience to help understand the structure and function of the brain. Applications to restore motor function to neurologically impaired individuals have shown promise to restore functionality. Cortical electrodes have been unable to achieve the longevity and stability to be employed as a viable clinical option. A constraint on longevity is the formation of a glial scar around an implant. It is proposed that reactions are due to two modes: a macro mode and a micro mode. The macro mode is a shear stress, differential-motion effect caused by a hard implant in soft neural tissue. The micro mode is a mechanotransduction mechanism where cellular pathways activate based on substrate stiffness. The first aim will investigate the cell micro/durotaxis response by using a controllable-stiffness material system to analyze the cellular response via immunohistochemistry (IHC). The second aim will investigate the effect of macro/shear stress by using a mechanically dynamic nanocomposite to gauge tissue response via IHC. The third aim is to assess the tissue response via electrophysiology by using a nanocomposite- encapsulated electrode. Immunohistochemisty of implants and electrophysiology of electrodes will provide quantitative data to differentiate performance of materials. The proposed work is designed to fuse neuroscience and neural engineering viewpoints to merge the fields to understand the fundamentals that will be vital in curing neural disorders and designing future neural devices. The focus of the study is on the cellular response to implant stiffness, and information gained in this study will be broadly applicable to many health arenas. Material stiffness has been implicated in stem cell differentiation, cancer development, spinal cord regrowth, and tissue engineering among other fields. Increasing the longevity of cortical implants will also allow for clinical restoration of function and the investigation of neurological diseases. This study will provide the first comprehensive study of stiffness- based tissue responses to cortical implants in vivo.