Biomechanical Characterization of Human Cartilaginous End-Plate

描述（由申请人提供）： 摘要腰痛是美国一个主要的社会经济问题。虽然腰痛的确切原因尚不清楚，但椎间盘退变（lVD）已被认为是可能的主要病因。营养供应不足被认为是椎间盘退变的机制之一，并阻碍任何组织工程或修复尝试。由于IVD组织中材料的独特组成和结构以及机械-电化学耦合现象的复杂性，缺乏对人体IVD的转运特性的了解以及系统研究IVD中营养物质转运的适当理论模型。本研究的目的是通过测量人体IVD组织的输运特性来填补这一空白，并发展一种新的机械电化学输运理论和有限元模型来研究人体IVD中流体和溶质的输运。拟议的研究将侧重于确定人类腰椎软骨终板（CEP），这被认为是发挥重要作用的椎间盘营养和负荷分布的机电和运输性能。我们的假设是，与人关节软骨相比，人CEP更硬，对间质液和溶质更具渗透性，机械负荷通过改变组织水合作用影响该组织中的液体和溶质转运速率。本研究将追求两个具体目标。具体目标#1是确定各种机械应变下人体CEP的水力渗透率、固定电荷密度和电导率，从电导率数据获得离子扩散率，并开发运输特性（水力渗透率和溶质扩散率）与组织水合作用之间的新本构关系，以建立应变依赖性运输特性。具体目标#2是确定人CEP的压缩和剪切力学性能，并将材料性能与组织成分相关联。所获得的材料特性将用于开发新的人类IVD多相有限元模型，以系统地量化各种载荷条件下椎间盘内的物理化学环境。理论、数值工具、材料特性数据和测量技术的进步将对理解椎间盘退变的病因以及开发组织再生的新策略产生重大影响。 公共卫生相关性： 项目描述本项目的目的是确定人类软骨终板的力学和运输特性，并研究机械应变对流体和溶质运输的影响，以了解椎间盘退变的营养相关机制。

DESCRIPTION (provided by applicant): Abstract Low back pain is a major socio-economic concern in the United States. Although the exact cause for low back pain is unclear, degeneration of the intervertebral disc (lVD) has been implicated as a possible primary etiologic factor. Poor nutritional supply is believed to be one of the mechanisms for disc degeneration and hampers any tissue engineering or repair attempt. Due to the unique composition and structure of the materials and the complexity of the mechano-electrochemical coupling phenomena in IVD tissues, there is a lack of knowledge on transport properties of human lVDs and appropriate theoretical models for investigating nutrient transport in IVD systematically. The goal of this research is to fill this gap by measuring transport properties of human IVD tissues, and develop a new mechano-electrochemical transport theory and finite element model for investigating the transport of fluid and solute in human IVD. The proposed study will focus on determination of the electromechanical and transport properties of human lumbar cartilaginous end-plate (CEP), which is thought to play an important role in disc nutrition and load distribution. Our hypothesis is that human CEP, compared to human articular cartilage, is stiffer and more permeable to the interstitial fluid and solutes, and mechanical loading affects the rates of fluid and solute transport in this tissue by changing tissue hydration. Two specific aims will be pursued during this study. Specific Aim #1 is to determine hydraulic permeability, fixed charge density, and electrical conductivity of human CEP under various mechanical strains, obtain ion diffusivities from electrical conductivity data, and develop new constitutive relationships between transport properties (hydraulic permeability and solute diffusivity) and tissue hydration to establish strain-dependent transport properties. Specific Aim #2 is to determine the compressive and shear mechanical properties of human CEP and correlate the material properties to the tissue composition. The obtained material properties will be used in developing a new multiphasic finite element model of human IVD to systematically quantify the physicochemical environment within the disc under various loading conditions. The advance in theory, numerical tools, data on material properties, and measuring techniques will have a significant impact on understanding etiology of disc degeneration as well as on developing new strategies for tissue regeneration. PUBLIC HEALTH RELEVANCE: Project Narrative The goal of this project is to determine the mechanical and transport properties of human cartilaginous end- plate and investigate the effect of mechanical strain on the fluid and solute transport for understanding the nutrition-related mechanism of intervertebral disc degeneration.