Macro/Micro Substrate Stiffness and Effect on Rat Brain Cortex

描述（由申请人提供）：本研究的重点是研究基底刚度在组织对皮质植入物的反应中的作用，以便与神经组织建立更持久、更亲密的界面。皮层电极在帮助理解大脑结构和功能的神经科学方面已经取得了巨大的进步。用于恢复神经损伤患者运动功能的应用已经显示出恢复功能的希望。皮质电极一直无法达到作为一种可行的临床选择使用的寿命和稳定性。限制寿命的一个因素是植入物周围会形成胶质疤痕。提出反应有两种模式：宏观模式和微观模式。宏观模式是由硬植入物在软神经组织中引起的剪切应力、微分运动效应。微模式是一种机械转导机制，其中细胞通路根据基质刚度激活。第一个目的是通过使用可控制刚度材料系统通过免疫组织化学（IHC）分析细胞反应来研究细胞微/硬致性反应。第二个目标是研究宏观/剪切应力的影响，通过机械动态纳米复合材料来测量组织对IHC的反应。第三个目的是利用纳米复合材料封装电极，通过电生理学来评估组织反应。植入物的免疫组织化学和电极的电生理将为区分材料的性能提供定量数据。这项工作旨在融合神经科学和神经工程的观点，以融合这两个领域，以了解对治疗神经疾病和设计未来神经装置至关重要的基础知识。本研究的重点是细胞对植入物刚度的反应，本研究获得的信息将广泛适用于许多健康领域。材料刚度涉及干细胞分化、癌症发展、脊髓再生和组织工程等领域。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基于刚度的组织对体内皮质植入物反应的综合研究。

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.