AN INTEGRATED MODEL OF INTERVERTEBRAL DISC FUNCTION

椎间盘功能的综合模型

• 批准号: 6767698
• 负责人: IAN A. STOKES
• 金额: $ 35.6万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767698
• 关键词: computational neuroscience; densitometry; electrical potential; fluorescence microscopy; human tissue; intervertebral disk; physical model; postmortem; skeletal stress; vertebrae

DESCRIPTION (provided by applicant): The intervertebral disc is the largest avascular structure in the human body, with very low cellularity and largely without sensory innervation. It has a slow rate of tissue turnover and its viability depends primarily on transport of dissolved nutrients and metabolites, through long diffusion pathways. The disc has been implicated in painful conditions that affect a large proportion of the population. Epidemiological data suggest that long-term degenerative changes are more likely to produce these painful conditions than are acute overload injuries. Therefore, here we propose to combine existing and new information on disc tissue properties and structure into a coordinated theory of the whole disc behavior that can subsequently be applied to explain its healthy and pathological behavior. We will perform experiments to document intervertebral disc mechanical behavior, and compare these data with a new combined theory of mechanical, fluid, and chemical behavior of the disc's tissues and structure. This theory will be incorporated in a finite element model of the whole disc that will be refined based on the experimental data. Specifically: (1) Mechanical behavior will be documented by measurements of time-dependent load-displacement behavior of intervertebral discs and internal displacements. (2) Intervertebral disc swelling behavior will be documented over time by placing semi-constrained discs in baths of differing ionic concentrations and measuring volumetric increase, constraining force and intradiscal pressure. (3) Fluid flow and diffusion in the intervertebral disc will be measured under conditions of different end-plate permeability by recording the concentration of fluorescent dyes of different molecular weights. (4) Electrical potentials will be mapped at known positions in intervertebral discs subjected to time-varying displacements of the specimen with controlled boundary conditions (displacements and porosity of the end fittings). This theory will, in turn, provide a way to understand the relationships between the physical environment of the disc (mechanical, nutritional, etc.) and the local conditions that can influence its metabolism, eventual composition and function in three-dimensions.

描述（由申请人提供）： 椎间盘是人体最大的无血管结构，细胞数量非常少，并且基本上没有感觉神经支配。它的组织周转速度较慢，其活力主要取决于溶解的营养物质和代谢物通过长扩散途径的运输。椎间盘与影响大部分人口的痛苦状况有关。流行病学数据表明，长期退行性变化比急性超负荷损伤更有可能产生这些痛苦的情况。因此，在这里，我们建议将有关椎间盘组织特性和结构的现有信息和新信息结合到整个椎间盘行为的协调理论中，该理论随后可用于解释其健康和病理行为。 我们将进行实验来记录椎间盘的机械行为，并将这些数据与椎间盘组织和结构的机械、流体和化学行为的新组合理论进行比较。该理论将被纳入整个圆盘的有限元模型中，该模型将根据实验数据进行完善。具体来说： (1) 将通过测量椎间盘随时间变化的负载位移行为和内部位移来记录机械行为。 (2)通过将半约束椎间盘放置在不同离子浓度的浴中并测量体积增加、约束力和椎间盘内压力，记录椎间盘随时间的肿胀行为。 (3)通过记录不同分子量荧光染料的浓度，测量不同终板通透性条件下椎间盘内流体的流动和扩散。 (4) 将在受控边界条件（末端配件的位移和孔隙率）下样本随时间变化的位移的情况下，在椎间盘的已知位置处绘制电势图。反过来，该理论将提供一种方法来理解椎间盘的物理环境（机械、营养等）与可以影响其新陈代谢、最终组成和三维功能的局部条件之间的关系。