UC San Diego

The development and maintenance of joint shape is critical for cartilage and bone biomechanics, integrity, and homeostasis. During long bone development, variations in rates of chondrocyte proliferation, hypertrophy, and matrix production within the articulo-epiphyseal cartilage complex produce the wide range of joint shapes and relative proportions of anatomical features. Difference in shape due to growth, repair, or disease, may affect or reflect joint-scale biomechanics, such as range of motion, as well as tissue-scale mechanics, such as cartilage stiffness. This dissertation aims to elucidate the relationship between joint shape and function, as well as advance the understanding of how joint shapes evolve during growth and deform in the presence of altered biomechanics during repair and in disease. The shape of the femur was assessed using 3-D local point registration and global statistical shape modeling techniques in animal models of growth and repair, and in human pediatric hip disorders. During cartilage repair, large shape deviations at the bone-cartilage interface were associated with local articular surface recession and low cartilage stiffness, establishing the importance of joint shape in the maintenance of cartilage biomechanics. During normal development of proximal and distal femoral shape, deformations and strains at the bone-cartilage interface were found to be site-specific and coordinated with changes at local growth plates. In humans, proximal femora underwent differential, growth-associated deformations and anisotropic areal dilations at the femoral head, femoral neck, and greater trochanter, with highest growth rates during puberty. Lastly, in the study of Legg-Calvé-Perthes disease and slipped capital femoral epiphysis, two pediatric hip disorders, proximal femora exhibited substantial disease- and site-specific deformations relative to the asymptomatic femur, with associated changes in growth plate normal vectors, suggesting biological and biomechanical mechanisms of shape deformation. This work demonstrated correlative links between structural features of the osteochondral unit in the femur and the biomechanical properties of the articular cartilage. Delineation of regional biomechanics and morphological changes contribute to the understanding of the mechanobiology of the proximal and distal femur. In addition, metrics of displacement and strain provide tangible targets for the development of future shape modulation therapies