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.

Project Narrative Human skeletal deformities involving the jaw affect ~6% of all adults and are often associated with pain and poor function of the two temporomandibular joints (TMJ) that allow for movement of the lower jaw during talking and eating. Surgery to correct these jaw skeletal deformities, and thus obtain better oral function, is often helpful but can cause problems for the TMJ. This project will determine the biomechanical and biologic conditions of the TMJ for patients with jaw skeletal deformities, both before and after surgery, to understand how these surgeries affect how well the TMJ works and thus aide surgeons to have better surgical outcomes.