Biomechanical Characterization and Modeling of Human TMJ Disc

人类颞下颌关节盘的生物力学表征和建模

• 批准号: 8690569
• 负责人: Gregory John Wright
• 金额: $ 4.35万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8690569
• 关键词: Affect; Anatomy; Biomechanics; Cells; Charge; Clinical; Coupling; Data; Development; Diagnosis; Diagnostic; Early Diagnosis; Electric Conductivity; Elements; Environment; Event; Extracellular Matrix; Family suidae; Fibrocartilages; Functional disorder; Goals; Human; Human Development; Hydration status; Intervertebral disc structure; Ions; Jaw; Joints; Knee; Knowledge; Lead; Liquid substance; Lubrication; Magnetic Resonance Imaging; Malocclusion; Mandible; Mastication; Measures; Mechanics; Meniscus structure of joint; Metabolic; Metabolism; Methods; Modeling; Molecular; National Institute of Dental and Craniofacial Research; Nickel; Nutrient; Outcome; Outcome Study; Pathologic; Pathology; Pathway interactions; Patients; Permeability; Property; Protocols documentation; Relaxation; Replacement Therapy; Reporting; Research; Simulate; Solid; Stress; Structure of articular disc of temporomandibular joint; Temporomandibular Joint; Temporomandibular Joint Disorders; Testing; Tissues; Translating; United States National Institutes of Health; arthropathies; base; density; human data; in vivo; innovation; intervertebral disk degeneration; mathematical model; novel; public health relevance; regenerative therapy; research study; soft tissue; solute; success; three-dimensional modeling; tool

DESCRIPTION (provided by applicant): Temporomandibular joint (TMJ) disorder affects over 10 million people in the US each year. Despite ongoing research, there is a current lack of understanding in the TMJ biomechanics field related to human biomechanical function. This has been attributed to the low success rate of replacement therapy as well as the inability to manage progressive pathology of the joint. As a result, significant advances in research are essential to understand the pathophysiology of joint degeneration for early diagnosis and management. It is generally believed that pathological mechanical loadings, e.g. sustained jaw clenching or malocclusion, trigger a cascade of molecular events leading to TMJ disc degeneration, which has been implicated in over 30% of TMJ disorders. Our previous studies indicate that the nutrient concentrations dictate TMJ cell metabolism and matrix synthesis. Due to the technical difficulty of measuring the in vivo mechanical and nutrient environment inside the TMJ, a finite element model must be developed to simulate the effect of mechanical loading on the nutrient diffusivities inside the TMJ disc. A deeper understanding of the biomechanics, i.e. mechanical environment and effect on the nutrient environment, could lead to developments in TMJ disorder diagnosis and management. Therefore, the objective of this research study is to develop an accurate mathematical model (finite element model) based on the first ever human characterization of the human mechanical and transport properties. Our central hypothesis is that sustained mechanical loading can alter solute transport and nutrient levels in the TMJ disc as well as mechanical function resulting in disc derangement and degeneration. We further hypothesize that by testing human TMJ discs with porcine TMJ discs under the same protocol, we will better understand the relevance of the porcine model to the human. Aim 1: Determine mechanical properties of human and porcine TMJ discs and correlate the mechanical properties to the tissue composition. Aim 2: Determine strain-dependant transport properties of human and porcine TMJ discs. Aim 3: Develop 3D patient specific multiphasic mechano-electrochemical finite element model of the human TMJ disc. The outcome of this study will yield 1) a patient specific finite element model to build a pathway between biomechanics and pathobiology 2) the first study to characterize the biomechanical properties of the human TMJ disc 3) the first study to establish the porcine biomechanical model in reference to the human for developments in tissue replacements and regenerative therapies. Finally, the project will bring the clinical field crucial, non-invasive method to screen and manage progression of patients with TMJ disorders.

描述（由申请人提供）：在美国，颞下颌关节（TMJ）疾病每年影响超过1000万人。尽管研究正在进行中，但目前对TMJ生物力学领域与人体生物力学功能的关系还缺乏了解。这归因于替代疗法的低成功率以及无法控制关节的进展性病理。因此，重要的研究进展是必不可少的，以了解关节退变的病理生理学的早期诊断和管理。一般认为，病理性机械负荷，如持续的颌紧咬合或错颌合，引发一系列分子事件，导致TMJ椎间盘退变，这与30%以上的TMJ疾病有关。我们之前的研究表明，营养浓度决定TMJ细胞的代谢和基质合成。由于测量TMJ体内机械和营养环境的技术困难，必须建立有限元模型来模拟机械负荷对TMJ椎间盘内营养物质扩散率的影响。深入了解生物力学，即力学环境及其对营养环境的影响，将有助于TMJ疾病的诊断和治疗。因此，本研究的目的是建立一个精确的数学模型（有限元模型），基于人类对人类机械和运输特性的首次人类表征。我们的中心假设是，持续的机械负荷可以改变TMJ椎间盘的溶质转运和营养水平，以及导致椎间盘紊乱和退变的机械功能。我们进一步假设，通过在相同的方案下用猪TMJ椎间盘测试人类TMJ椎间盘，我们将更好地了解猪模型与人类的相关性。目的1：确定人和猪TMJ椎间盘的机械性能，并将机械性能与组织组成相关联。目的2：确定人类和猪TMJ椎间盘的菌株依赖转运特性。目的3：建立三维患者特异性的人TMJ椎间盘多相力学-电化学有限元模型。本研究的结果将产生1)建立患者特定的有限元模型，以建立生物力学和病理生物学之间的途径；2)首次研究人类TMJ椎间盘的生物力学特性；3)首次建立猪生物力学模型，以参考人类组织替代和再生治疗的发展。最后，该项目将为临床领域带来至关重要的非侵入性方法来筛查和管理TMJ疾病患者的进展。