Multiscale and Multimodal Structure-Function Analysis of Intervertebral Interfaces During Degeneration and Regeneration

退变和再生过程中椎间界面的多尺度和多模态结构功能分析

• 批准号: 9982743
• 负责人: Beth Gayle Ashinsky
• 金额: $ 5.05万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2022-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982743
• 关键词: Address; Animals; Architecture; Atomic Force Microscopy; Back Pain; Benchmarking; Biochemical; Biological; Biomechanics; Cartilage; Clinical; Clinical Treatment; Communities; Complex; Diagnosis; Diagnostic; Disease; Engineering; Ensure; Evaluation; Extracellular Matrix; Failure; Fibrocartilages; Generations; Growth; Height; Histology; Human; Hybrids; In Vitro; Intervention; Intervertebral disc structure; Joints; Length; Magnetic Resonance Imaging; Mechanics; Mediating; Mentors; Modeling; Motion; Musculoskeletal; Natural regeneration; Nature; Operative Surgical Procedures; Orthopedics; Oryctolagus cuniculus; Pathologic; Pathology; Physicians; Population; Positioning Attribute; Pre-Clinical Model; Prevalence; Procedures; Process; Property; Proteoglycan; Rattus; Replacement Arthroplasty; Reporting; Research; Scanning Electron Microscopy; Scientist; Structure; Structure-Activity Relationship; Tail; Techniques; Testing; Time; Tissue Engineering; Tissues; Training; Translations; United States; Vertebral column; Weight-Bearing state; Work; aging population; bone; career; clinically relevant; flexibility; implantation; improved; in vivo; interfacial; intervertebral disk degeneration; multimodality; nucleus pulposus; reduce symptoms; response; second harmonic; second harmonic generation imaging; soft tissue; success; tool; treatment strategy; vertebra body

Abstract Intervertebral disc (IVD) degeneration and associated back pain place a significant burden on the population. As a multiphasic tissue-complex, the interfaces between the subcomponents of the IVD are integral to its normal function. Despite this, there has been little focus in the research community on a comprehensive evaluation of the interfaces of the IVD during degeneration and regeneration. The first objective of this proposal is to quantitatively evaluate the interfaces between the cartilage endplate-annulus fibrosus (EP-AF) and annulus fibrosus-nucleus pulposus (AF-NP) across multiple length scales in healthy and degenerative discs. This will be accomplished via two Specific Aims. Aim 1 will probe the multi-scale structure-mechanics relationships of the interfacial regions (EP-AF, AF-NP) of healthy human and rabbit IVDs. The interfacial regions of human and rabbit IVDs will be evaluated at the microscale via analysis of biochemical content, histology, scanning electron microscopy (SEM), atomic force microscopy (AFM) and second harmonic generation (SHG) imaging. Macroscale properties will be characterized by MRI (T2 mapping, UTE T2, T1r) and biomechanical testing (in compression and tension). In Aim 2, the impact of disc degeneration on the structure and mechanics of EP-AF and AF-NP interfaces at different length scales will be evaluated. For this Aim, interfacial properties of degenerated rabbit and human discs will be assessed at the micro and macroscale using the techniques outlined Aim 1 in order to elucidate how structure and function change with IVD degeneration. Finally, in Aim 3, these same micro- to macro-scale analyses will be applied to regenerating discs. Our group has advanced biologic total disc replacements (endplate-modified disc-like angle-ply structures, eDAPS) for the treatment of advanced stage degeneration. Translation of these eDAPS will require that the interfacial regions of these engineered discs, between the EP-AF and AF-NP match native tissue benchmarks in order to ensure long-term in vivo function. This Aim will assess the interfacial regions of regenerating discs at multiple length scales and determine how these properties mature in engineered tissues both in vitro and with time post-implantation in a rabbit model of total disc replacement. The results from this study will further our understanding of the structure-function relationships of normal and degenerated interfaces in the IVD, and in engineered tissues. Overall, this work has the potential to significantly improve the diagnosis and clinical treatment of back pain associated with disc degeneration.!

抽象的 椎间盘（IVD）退变和相关的背痛给人们带来了沉重的负担。 作为一个多相组织复合体，IVD 子组件之间的界面是其不可或缺的组成部分。 功能正常。尽管如此，研究界很少关注全面的 退化和再生过程中 IVD 界面的评估。此次活动的第一个目标 建议是定量评估软骨终板-纤维环（EP-AF）之间的界面 以及健康和退化的多个长度尺度的纤维环-髓核（AF-NP） 光盘。这将通过两个具体目标来实现。目标 1 将探讨多尺度结构力学 健康人和兔 IVD 界面区域（EP-AF、AF-NP）的关系。界面 人类和兔子 IVD 的区域将通过生化含量分析在微观尺度上进行评估， 组织学、扫描电子显微镜 (SEM)、原子力显微镜 (AFM) 和二次谐波 一代（SHG）成像。宏观特性将通过 MRI（T2 映射、UTE T​​2、T1r）进行表征 和生物力学测试（压缩和拉伸）。在目标 2 中，椎间盘退变对 将评估不同长度尺度下 EP-AF 和 AF-NP 界面的结构和力学。为了这 目的，退化的兔子和人类椎间盘的界面特性将在微观和 使用目标 1 概述的技术进行宏观尺度分析，以阐明结构和功能如何随着 IVD 变性。最后，在目标 3 中，这些相同的微观到宏观分析将应用于再生 光盘。我们组拥有先进的生物全椎间盘置换术（终板改良椎间盘状角层 结构，eDAPS）用于治疗晚期退化。这些 eDAPS 的翻译需要 这些工程椎间盘的 EP-AF 和 AF-NP 之间的界面区域与天然组织相匹配 基准以确保长期的体内功能。该目标将评估界面区域 再生多个长度尺度的椎间盘，并确定这些特性如何在工程组织中成熟 在体外和植入后一段时间内在兔全椎间盘置换模型中进行的研究。由此得出的结果 研究将进一步加深我们对正常和退化的结构与功能关系的理解 IVD 和工程组织中的界面。总体而言，这项工作有可能显着改善 椎间盘退变相关背痛的诊断和临床治疗！