Experimental and numerical investigation of temporal and spatial effects induced by motion and load in joint biomechanics: A study of joint loading in vivo, functional imaging, and finite element modeling with focus on articular cartilage

Joint diseases are a leading cause of disability worldwide, and there is a tremendous concern about how joint motion and weight bearing impact on joint health. It is generally accepted that joint disuse and overuse both cause cartilage degradation, while moderate loading within physiological range help maintain cartilage integrity; however, the mechanism mediating the dichotomy of mechanical factors in improving or damaging cartilage functional capacity remains largely unknown. It is of significant interest from both a basic science and a clinical perspective to elucidate the complex temporal and spatial effects of joint motion and load bearing in joint biomechanics. Furthermore, a prerequisite for research efforts towards this direction is the establishment and analysis of suitable animal models (preferably rodent) that mimic the normal and pathologic motion-load patterns in humans. Although numerous in vitro and in vivo studies have been performed to date, due to the apparent experimental difficulties such as the small size, little has been achieved for ideal experimental and analytical research methodologies in small animal models. In this dissertation, experimental and numerical approaches were taken in a series of challenging joint biomechanics research projects, and the purpose of the dissertation was to elucidate the clinical relevant temporal and spatial effect of motion-load induced mechanical loading applied on the joint. We developed and validated a cutting-edge joint motion and loading system that offers precise control of joint motion and compressive impact load to quantitatively study the mechanoresponsiveness in joint tissues. We explored the early response of cartilage to joint immobilization and remobilization. We created the first FE model in rodent model based on a contrast agent enhanced high-resolution micro-CT imaging approach to characterize the local spatial mechanical environment in which chondrocytes sense and respond. The developed joint motion and load system demonstrated remarkable reliability and reproducibility for challenging protocols. The in vivo temporal experiments showed that immobilization of joints may cause cartilage degeneration in a short time, while early intervention of moderate motion that produced biomechanical signals to suppress the acute inflammatory effect can reverse this catabolic process, and overloading produced similar results to that observed from immobilization. The low cost micro-CT arthrography approach using a contrast agent to create high-resolution three-dimensional (3D) geometries of soft tissues in rat joints proved practical and efficient. The FE modeling result of rat knee joint loading showed the stress distribution that supports our hypothesis that gene expression of important mediators is a function of stress in that particular region. The knowledge obtained through these studies may provide more insight into the underlying mechanism orchestrating the relationship between motion, loading and the corresponding biological responses in cartilage, and may further help treat Osteoarthritis and other joint disorders by contributing to design effective motion-based therapies.