Biomechanical Characterization and Modeling of Human TMJ Disc

描述(由申请者提供)：在美国，每年有超过1000万人患有TMJ疾病。尽管目前正在进行研究，但目前对与人类生物力学功能相关的TMJ生物力学领域缺乏了解。这归因于替代疗法的成功率很低，以及无法处理关节的进行性病理。因此，研究方面的重大进展对于了解关节退行性变的病理生理学以便早期诊断和治疗至关重要。通常认为，病理性机械负荷，如持续咬合或错牙合，会触发一系列分子事件，导致TMJ盘退变，超过30%的TMJ疾病与此有关。我们以前的研究表明，营养浓度决定了TMJ细胞的新陈代谢和基质合成。由于测量TMJ体内力学和营养环境的技术难度较大，必须建立有限元模型来模拟机械载荷对TMJ盘内营养物质扩散的影响。深入了解TMJ的生物力学，即力学环境和对营养环境的影响，将有助于TMJ疾病的诊断和治疗。因此，本研究的目的是开发一种精确的数学模型(有限元模型)，该模型基于首次人类对人类机械和运输特性的表征。我们的中心假设是，持续的机械负荷可以改变TMJ盘中的溶质运输和营养水平，以及导致盘错乱和退化的机械功能。我们进一步假设，通过在相同的方案下测试人的TMJ盘和猪的TMJ盘，我们将更好地理解猪模型与人类的相关性。目的1：测定人和猪TMJ间盘的力学性能，并将其与组织成分进行相关性分析。目的2：测定人和猪TMJ盘的应变依赖运输特性。目的3：建立人颞下颌关节盘三维多相机械-电化学有限元模型。这项研究的结果将产生1)建立生物力学和病理生物学之间的通路的患者特有的有限元模型2)第一个表征人类TMJ盘生物力学特性的研究3)第一个参照人类建立猪生物力学模型的研究，用于组织替换和再生治疗的发展。最后，该项目将为临床领域带来关键的、非侵入性的方法来筛选和管理TMJ疾病患者的进展。

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.