AN INTEGRATED MODEL OF INTERVERTEBRAL DISC FUNCTION

描述(由申请人提供)： 椎间盘是人体内最大的无血管结构，细胞密度很低，大部分没有感觉神经支配。它的组织周转速度很慢，其生存能力主要取决于溶解的营养物质和代谢物的运输，通过长时间的扩散路径。这种椎间盘与痛苦的情况有关，影响了很大一部分人口。流行病学数据表明，与急性超负荷损伤相比，长期的退行性变化更有可能产生这些痛苦的情况。因此，在这里，我们建议将现有的和新的关于椎间盘组织属性和结构的信息结合到一个关于整个椎间盘行为的协调理论中，该理论可以随后应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力学行为，并将这些数据与一种关于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。这一理论将被合并到整个圆盘的有限元模型中，该模型将基于实验数据进行改进。具体地说：(1)力学行为将通过测量椎间盘和内部位移随时间变化的载荷-位移行为来记录。(2)随着时间的推移，通过将半约束的椎间盘放置在不同离子浓度的浴液中，并测量体积增长、约束力和盘内压力，将记录椎间盘的肿胀行为。(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的流体在椎间盘内的流动和扩散。(4)在具有受控边界条件(末端配件的位移和孔隙率)的情况下，受试件的时变位移的影响，将在椎间盘中的已知位置绘制电势图。这一理论将反过来提供一种方法来理解光盘的物理环境(机械、营养等)之间的关系。以及局部条件对其新陈代谢、最终组成和功能的三维影响。

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.