Sesamoid bones, such as the patella, are small bones that are embedded within tendons in regions that wrap around and impinge against bony prominences. Sesamoid bones can play an important role in normal joint function, often increasing the mechanical advantage of the associated muscle-tendon unit and reducing the amount of wear and damage that can arise during repetitive joint motion. For more than a century, anatomists and other biological scientists have debated about what causes sesamoid bones to form and why certain individuals have certain sesamoids while others do not. This thesis presents four studies that investigate the relationship between intrinsic and extrinsic factors in the regulation of sesamoid formation, development, and ossification.

The first study reviews the literature on sesamoids and explores the question of genetic control of sesamoid development. An examination of radiographs of 112 people demonstrated that the relatively infrequent appearances of the fabella (in the lateral gastrocnemius tendon of the knee) and os peroneum (in the peroneus Iongus tendon of the foot) are related within individuals (p < 0.01). This finding suggests that the tendency to form sesamoids may be linked to intrinsic genetic factors. Evolutionary character analyses suggest that the formation of these sesamoids in humans may be a consequence of phylogeny. These observations indicate that variations of intrinsic factors may interact with extrinsic mechanobiological factors to influence sesamoid development and evolution.

The second study examines the role of mechanical loading on the prenatal formation of sesamoids. It presents a time-dependent adaptation simulation to test the hypothesis that the loading history in a developing wrap-around tendon can regulate the formation and development of a sesamoid structure within the tendon substance. The adaptation simulation is based on the fundamental assumptions that (1) high intermittent tensile strain causes an increase in collagen content and cross-linking that leads to an increase in tissue stiffness;​ and (2) high intermittent hydrostatic fluid pressure causes chondrometaplasia with an associated increase in aggrecan content, which leads to a decrease in tissue permeability. The simulation predicted a cartilage-like tissue embedded within a band of fibrous-like tissue. This approach builds on previous analytical and experimental approaches to understanding chondrometaplasia in tendons to show, for the first time, how the initial formation of a sesamoid can be regulated by mechanobiological factors.

The third study considers the effects of mechanical loading on the unique endochondral ossification process in sesamoids. Bone formation within sesamoids often begins with multiple ossification nuclei. We used two-dimensional finite element analysis to predict the distributions of octahedral shear stress, hydrostatic stress, and an osteogenic stimulus in an idealized model of a sesamoid cartilage subjected to in vivo loading. We examined the influence of sesamoid joint conformity. The results suggest that nonconformity between the sesamoid cartilage and its articulating surface, which arises during early development, produces higher contact pressures within the sesamoid, compared to conforming joints, and leads to a thicker articular cartilage layer. For a nonconforming joint surface, the results suggest that ossification is favored anywhere within a broad internal region of the sesamoid, while a layer at the articular surface will remain cartilaginous. These findings highlight the subtle differences between ossification processes in epiphyses and sesamoids, indicating that the mechanical stress environment in sesamoids produces a diffuse stimulus leading to the onset of ossification and that the degree of joint nonconformity may influence the thickness of the articular cartilage layer.

The fourth study examines the extent to which linear elastic models are appropriate for predicting the mechanical response of cartilage under physiologic loading. It investigates how incorporating a fluid-solid (poroelastic) model of tissue behavior affects the results that were derived in the previous study with the use of a linear elastic material model. The results indicate that fluid flow is negligible under physiologic loading conditions. For all combinations of material properties that we examined, predictions of cartilage ossification and maintenance based on the poroelastic material model were similar to those predicted by the previous elastic analyses. These findings indicate that the short-term response of the cartilage mass under physiologic loading frequencies and conditions can be adequately characterized by single-phase models of cartilage behavior.

The results of this thesis indicate that normal sesamoid formation and development are dependent on more than just the presence of a genetic blueprint. Mechanical loading associated with differential growth, muscular contraction, and locomotion is a critical factor that guides in vivo sesamoid development. A major strength of this work is that it builds on previous investigations of soft skeletal connective tissue behavior and provides a consistent framework for considering the effects of mechanical loading on the response of biological soft tissues.