COBRE P4: FLUID AND SOLUTE TRANSPORT IN HUMAN TEMPOROMANDIBULAR JOINT DISC

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 项目描述： 本项目的长期目标是阐明流体和溶质运输在人类颞下颌关节盘的组织机械功能和细胞营养中的作用，以描绘TMD的生物力学病因，并开发新的策略来恢复组织功能。该建议的具体目的是：1）评估机械应变对人类颞下颌关节盘的传输特性的影响，并建立传输特性和组织生化成分之间的本构关系; 2）建立流体流动依赖于盘负载支持和润滑的机制。为了实现目标1，我们将：a）确定不同机械应变下正常人颞下颌关节盘的透水率、固定电荷密度和电导率; B）从电导率数据获得离子扩散率，并开发运输特性（透水率和溶质扩散率）与组织水合之间的新本构关系，以建立应变相关的运输特性。为了实现目标2，我们将确定时间依赖性流体压力，流体负载支持，和摩擦系数的正常人颞下颌关节盘持续的机械负荷下，和相关的流体负载支持和摩擦系数间质流体压力。这些研究将为椎间盘退变的生物运输相关机制提供新的见解。为了实现我们的长期目标，我们将进一步开发一个新的多相机械电化学有限元模型的人类颞下颌关节盘，这将提供详细的机械应力，应变，流体压力，营养浓度，电位，流体流动，和运输的营养物质在生理或病理负荷条件下的颞下颌关节盘。本研究亦将探讨关节盘细胞对这些物理化学信号的生物反应，以充分阐明颞下颌关节关节盘退变的生物力学病因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project Description: The long-term goal of this project is to elucidate the roles of fluid and solute transport in tissue mechanical function and cell nutrition of the human TMJ disc for delineating the biomechanical etiology of TMDs and to develop new strategies for restoring tissue function. The specific aims of this proposal are to: 1) evaluate the effect of mechanical strain on the transport properties of the human TMJ disc and develop constitutive relationships between transport properties and tissue biochemical composition; 2) establish fluid flow dependent mechanisms for disc loading support and lubrication. To accomplish aim 1, we will: a) determine hydraulic permeability, fixed charge density, and electrical conductivity of the normal human TMJ disc under various mechanical strains; b) 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. To accomplish aim 2, we will determine time-dependent fluid pressure, fluid load support, and friction coefficient of the normal human TMJ disc under sustained mechanical loading, and correlate fluid load support and friction coefficient to interstitial fluid pressure. These studies will provide new insights into a bio-transport related mechanism for disc degeneration. To achieve our long-term goal, we will further develop a new multiphasic mechano-electrochemical finite element model of the human TMJ disc which will provide details of mechanical stress, strain, fluid pressure, nutrient concentrations, electrical potential, fluid flow, and transport of nutrients within the TMJ disc under physiological or pathological loading conditions. Studies will also be conducted to understand the biological response of disc cells to these physicochemical signals for fully elucidating biomechanical etiology of TMJ disc degeneration.