ATTRACT: Assessment of Temporomandibular JoinT MoRphology, Mechanics, And Mechanobiology in Class II and III Target and Surgical Phenotypes

项目摘要 颅面部骨骼畸形包括下颌骨后缩(MR)，这是II类骨骼畸形 发生在~5%的个体中，以及下颌前突(MP)，这是发生的III类骨骼畸形 在约1%的个人中。颅面骨骼畸形和TMJ疾病之间存在关联， 43%的II类畸形和20%的III类畸形有退行性改变，但只有3%的I类畸形有退行性改变(即没有 骨骼畸形)。此外，第二类女性通常有较小的髁突，其风险要高得多。 导致TMJ功能障碍。尽管有越来越多的证据表明头面部骨骼畸形可能 是TMJ疾病发展的重要危险因素，只有研究形态参数才有 没有给出任何关于生物机制或因果关系的见解。此外，正颌 手术通过调整骨骼形态是有益的，但其对TMJ功能的效果却知之甚少。 关节形态驱动生物力学，生物力学反过来调节关节组织重塑中的力学生物学。 确定颅面形态、TMJ生物力学和关节之间的力学关系 机制生物学，导致了对TMJ疾病的病因和性别差异的更好的理解。 具体地说，较小的髁突和较短的下颌骨增加了女性TMJ的负荷、接触应力和能量 密度，同时降低组织养分利用率和细胞活力，导致病理性TMJ 改建。本申请的目的是采用相同的TMJ形态学的综合方法， 力学和机械生物学，但在第二类和第三类表型的背景下。我们的总体假设 是TMJ的机械负荷大小，以及组织养分利用率和细胞活力 具有I、II和III类表型的骨骼成熟个体之间存在显著差异。更具体地说 我们假设第二类女性的TMJ具有最高的机械负荷，最低的组织营养 可利用性，以及由于不成比例的小髁状突和短的下颌骨而导致的最低细胞存活率，以及 正颌外科可以改善TMJ的生物力学和力学生物学，从而提供机械洞察力。 我们提出了三个具体目标：(1)确定颅面形态和TMJ生物力学的差异 具有I类、II类和III类表型的个体之间。(2)确定TMJ的力学生物学差异 具有I、II和III类表型的个体之间的指标。(3)确定TMJ形态的差异， II类和III类表型正颌外科手术前后的力学、机械生物学。 该项目结合了颅面部畸形的形态特征和治疗方面的专业知识。 NIDCR临床中心内调查人员，用TMJ生物力学和力学生物学测量 以及校外申请者的模特专长。结果将(I)确定临床可测量的风险 骨骼畸形患者TMJ障碍的因素：(Ii)证明正颌外科手术修复的益处 TMJ健康，以及(Iii)指导未来针对患者的手术计划，以优化术后TMJ功能。

Project Summary Craniofacial skeletal deformities include mandibular retrognathism (MR), which is Class II skeletal deformity occurring in ~5% of individuals, and mandibular prognathism (MP), which is Class III skeletal deformity occurring in ~1% of individuals. There is an association between craniofacial skeletal deformity and TMJ disorders, with degenerative changes in 43% of Class II and 20% of Class III deformities, but only in 3% of Class I (i.e., no skeletal deformity). Moreover, Class II females which typically have smaller condyles, have a much higher risk to develop TMJ dysfunction. Even though there is increasing evidence that craniofacial skeletal deformity may be an important risk factor for the development of TMJ disorders, only studying morphological parameters has not given any insight into a biological mechanism or a cause-effect relationship. Additionally, orthognathic surgery can be beneficial by adjusting skeletal morphology, but its efficacy on TMJ function is poorly understood. Joint morphology drives biomechanics, which in turn regulates mechanobiology in joint tissue remodeling. Identifying the mechanistic relationships between craniofacial morphology, TMJ biomechanics, and joint mechanobiology, has led to a better understanding of the etiology and sex disparity of TMJ disorders. Specifically, smaller condyles and shorter mandibles increase female TMJ loads, contact stresses and energy density, while decreasing both tissue nutrient availability and cell viability, leading to pathological TMJ remodeling. The objective of this application is to take this same integrated approach of TMJ morphology, mechanics, and mechanobiology but in the context of Class II and III phenotypes. Our over-arching hypothesis is that mechanical loading magnitude, as well as tissue nutrient availability and cell viability, of the TMJ are significantly different between skeletally mature individuals with Class I, II, and III phenotypes. More specifically we hypothesize that the TMJ in Class II females has the highest mechanical loading, lowest tissue nutrient availability, and lowest cell viability due to disproportionally small condyle and short mandible, and that orthognathic surgery can improve both TMJ biomechanics and mechanobiology, thus giving mechanistic insight. We propose three specific aims (1) Determine differences in craniofacial morphology and TMJ biomechanics between individuals with Class I, II, and III phenotypes. (2) Determine differences in TMJ mechanobiological indicators between individuals with Class I, II, and III phenotypes. (3) Determine differences in TMJ morphology, mechanics, mechanobiology before and after orthognathic surgery in individuals with Class II and III phenotypes. This project combines expertise in morphologic characterization and treatment of craniofacial deformities of NIDCR Clinical Center intramural investigators, with the TMJ biomechanics and mechanobiology measurement and modeling expertise of the extramural applicants. The outcomes will (i) identify clinically measurable risk factors for TMJ disorders in skeletal deformity patients, (ii) justify the benefit of orthognathic surgery for restoring TMJ health, and (iii) guide future patient-specific surgical planning to optimize post-op TMJ function.