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，细胞含量非常低，基本上没有感觉神经支配。它具有缓慢的组织周转率，其生存能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疼痛状况有关。流行病学数据表明，长期的退行性变化比急性过载损伤更容易产生这些疼痛状况。因此，在这里，我们建议将联合收割机现有的和新的信息，椎间盘组织的性质和结构到一个协调的理论，整个椎间盘的行为，随后可以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，并将这些数据与椎间盘组织和结构的力学，流体和化学行为的新组合理论进行比较。该理论将被纳入一个有限元模型的整个光盘，将完善的基础上的实验数据。具体而言：（1）将通过测量椎间盘的时间依赖性载荷-位移行为和内部位移来记录力学行为。(2)通过将半限制型椎间盘置于不同离子浓度的浴槽中并测量体积增加、限制力和椎间盘内压，记录随时间推移的椎间盘肿胀行为。(3)通过记录不同分子量的荧光染料的浓度，在不同终板渗透性的条件下测量椎间盘中的流体流动和扩散。(4)将在椎间盘中的已知位置绘制电势，椎间盘经受具有受控边界条件（端部配件的位移和孔隙度）的样本的时变位移。这一理论将反过来提供一种方法来理解椎间盘的物理环境（机械，营养等）之间的关系。以及可以影响其代谢、最终组成和三维功能的局部条件。

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.