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

项目摘要 颅面骨骼畸形包括下颌后缩（MR），属于II类骨骼畸形 约5%的个体发生，以及下颌无颌症（MP），这是III类骨骼畸形， 约1%的人。颅面骨骼畸形和颞下颌关节紊乱病之间存在关联， 43%的II类和20%的III类畸形中存在退行性变化，但I类仅为3%（即，没有 骨骼畸形）。此外，II类女性通常具有较小的髁突，具有更高的风险 导致颞下颌关节功能障碍尽管越来越多的证据表明颅面骨骼畸形可能 是颞下颌关节疾病发展的一个重要危险因素，只有研究形态学参数， 没有给出任何关于生物机制或因果关系的见解。此外，正颌 手术可以通过调整骨骼形态而获益，但其对颞下颌关节功能的作用知之甚少。 关节形态驱动生物力学，生物力学反过来又调节关节组织重塑中的机械生物学。 确定颅面形态、颞下颌关节生物力学和关节之间的机械关系 机械生物学，导致了更好地了解颞下颌关节疾病的病因和性别差异。 具体来说，较小的髁突和较短的下颌骨增加女性颞下颌关节负荷，接触应力和能量 密度，同时降低组织营养物质的可用性和细胞活力，导致病理性TMJ 重塑本申请的目的是采用TMJ形态学的相同综合方法， 力学和机械生物学，但在II类和III类表型的背景下。我们的过度假设 TMJ机械负荷量以及组织营养素的可利用性和细胞活力是 具有I类、II类和III类表型的生殖成熟个体之间存在显著差异。更具体 我们假设II类女性的颞下颌关节具有最高的机械负荷，最低的组织营养 由于髁突小和下颌骨短， 正颌外科手术可以改善颞下颌关节的生物力学和机械生物学，从而提供机械见解。 我们提出了三个具体的目标：（1）确定颅面形态和颞下颌关节生物力学的差异 I类、II类和III类表型个体之间的差异。(2)确定TMJ机械生物学的差异 具有I类、II类和III类表型的个体之间的指标。(3)确定颞下颌关节形态的差异， 在II类和III类表型的个体中进行正颌手术前后的力学、机械生物学。 该项目结合了形态学特征和颅面畸形治疗的专业知识， NIDCR临床中心内部研究人员，进行TMJ生物力学和机械生物学测量 和模特专业知识。结果将（i）确定临床可测量的风险 骨骼畸形患者TMJ疾病的因素，（ii）证明正颌外科手术的好处， 颞下颌关节健康，和（iii）指导未来的患者特定的手术计划，以优化术后颞下颌关节功能。

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.