Biophysical Modeling of Fluid and Solute Transport in the TMJ Disc

颞下颌关节盘中液体和溶质运输的生物物理模型

• 批准号: 7589976
• 负责人: Hai Yao
• 金额: $ 11.13万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7589976
• 关键词: Affect; Biochemical; Biological; Biomechanics; Cartilage; Cell physiology; Cells; Charge; Coupling; Data; Diagnostic; Electric Conductivity; Elements; Environment; Etiology; Extracellular Matrix; Failure; Family suidae; Friction; Functional disorder; Future; Goals; Health; Human; Human body; Hydration status; Intercellular Fluid; Intervertebral disc structure; Ions; Jaw; Joints; Knee joint; Knowledge; Lead; Liquid substance; Lubrication; Measurement; Measures; Mechanical Stress; Mechanics; Methods; Modeling; Necrosis; Nutrient; Nutritional; Pathology; Pathway interactions; Permeability; Physiological; Play; Porosity; Property; Role; Signal Transduction; Stress; Structure; Structure of articular disc of temporomandibular joint; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Theoretical model; Time; Tissues; Treatment Protocols; United States; Water; Weight-Bearing state; Work; articular cartilage; density; design; electrical potential; fluid flow; insight; intervertebral disk degeneration; novel; nutrition; pressure; public health relevance; regenerative; response; soft tissue; solute; tool

DESCRIPTION (provided by applicant): Temporomandibular joint disorders (TMDs) are an important national health problem affecting more than 10 million people in the United States. Although the exact cause of TMDs is unclear, the temporomandibular joint (TMJ) disc pathophysiology (i.e., disc derangement and degeneration) is central to many TMDs. Poor nutritional supply to the TMJ disc as well as failure of mechanical function caused by pathological mechanical loading are believed to be the major biomechanical mechanisms for TMJ disc derangement and degeneration. The long-term goal of this project is to elucidate the roles of fluid and solute transport in TMJ disc mechanical function and cell nutrition for delineating the biomechanical etiology of TMDs in order to develop new strategies for restoring tissue function. Due to the unique composition and structure of the materials in the TMJ disc, as well as the complexity of the mechano-electrochemical coupling phenomena, there is a lack of knowledge about transport properties of the TMJ disc and appropriate theoretical models for investigating fluid and nutrient transport in the TMJ disc systematically. Therefore, the Specific Aims of this proposal are to: 1) evaluate the effect of mechanical strain on the transport properties of the TMJ disc and develop constitutive relationships between transport properties and tissue biochemical composition; 2) examine the effect of changes in fluid transport properties on the tissue mechanical function and establish fluid flow dependent mechanisms for disc loading support and lubrication. To accomplish Specific Aim 1, we will: a) determine hydraulic permeability, fixed charge density, and electrical conductivity of porcine 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 Specific Aim 2, we will determine time-dependent interstitial fluid pressure, fluid load support, and friction coefficient of porcine 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 and provide baseline material properties for developing biomechanical model to fully understand TMJ disc function and pathology. This work will support future R01 applications in which we will propose to develop a new multiphasic mechano-electrochemical finite element model of the 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. We will also propose to study the biological response of disc cells to these physicochemical signals for fully elucidating biomechanical etiology of TMJ disc degeneration. Public Health Relevance: The goal of this project is to elucidate the roles of fluid and solute transport in tissue mechanical function and cell nutrition of the temporomandibular joint (TMJ) disc in order to delineate the biomechanical etiology of TMJ disorders and to develop novel, less-invasive diagnostic tools and new strategies for restoring tissue function. Therefore, this project will establish baseline measurements for the pig and generate biomechanical models that can be tested. In future studies we will use the pig to test these models further, compare different regenerative regimens, as well as design and evaluate human replacement TMJ tissues.

描述(申请人提供)：颞下颌关节紊乱病(TMD)是一个重要的国家健康问题，在美国有1000多万人受到影响。虽然TMDs的确切原因尚不清楚，但TMJ的椎间盘病理生理学(即关节盘的紊乱和退变)是许多TMDs的核心。病理性机械负荷导致的TMJ盘营养不良和机械功能衰竭是TMJ盘紊乱和退变的主要生物力学机制。本项目的长期目标是阐明液体和溶质运输在TMJ关节盘机械功能和细胞营养中的作用，以阐明TMDS的生物力学病因，从而开发新的组织功能恢复策略。由于TMJ盘中物质的独特组成和结构，以及机械-电化学耦合现象的复杂性，目前对TMJ盘中的传输特性缺乏了解，也缺乏合适的理论模型来系统地研究TMJ盘中的流体和营养物质的传输。因此，该建议的具体目的是：1)评估机械应变对TMJ椎间盘传输特性的影响，并建立传输特性与组织生化成分之间的本构关系；2)检测流体传输特性的变化对组织机械功能的影响，并建立用于椎间盘载荷支持和润滑的流体依赖机制。为了实现特定的目标1，我们将：a)测定不同机械应变下猪TMJ圆盘的水力渗透性、固定电荷密度和电导率；b)从电导率数据中获得离子扩散系数，并建立传输特性(水力渗透性和溶质扩散系数)和组织水化之间的新的本构关系，以建立依赖应变的传输特性。为了实现特定的目标2，我们将测定持续机械载荷下猪TMJ关节盘随时间变化的间质流体压力、流体载荷支承和摩擦系数，并将流体载荷支承和摩擦系数与间质流体压力进行关联。这些研究将为了解关节盘退变的生物运输相关机制提供新的见解，并为建立生物力学模型以全面了解TMJ的功能和病理提供基础材料特性。这项工作将支持未来的R01应用，其中我们将建议开发一个新的TMJ盘的多相机械-电化学有限元模型，该模型将提供在生理或病理负载条件下TMJ盘内的机械应力、应变、流体压力、营养物质浓度、电位、流体流动和营养物质传输的详细信息。我们还将建议研究椎间盘细胞对这些物理化学信号的生物反应，以全面阐明TMJ退变的生物力学病因。公共卫生相关性：本项目的目标是阐明液体和溶质运输在TMJ关节盘组织机械功能和细胞营养中的作用，以揭示TMJ疾病的生物力学病因，并开发新的、侵入性较小的诊断工具和恢复组织功能的新策略。因此，该项目将为猪建立基线测量，并生成可以测试的生物力学模型。在未来的研究中，我们将使用猪来进一步测试这些模型，比较不同的再生方案，以及设计和评估人类TMJ替代组织。