The knee menisci are commonly injured, and do not heal well as a result of their minimal vascularity and severe loading environment. Further, removal of the menisci is detrimental to the long term health of the knee joint. This objective of this body of work was to implement an integrated approach to better understand the function of the menisci as it relates to their fine structure and composition. This approach included mechanical, structural and biochemical analyses, of the menisci using a bovine model.

A thorough assessment of the relevant literature led to the conclusion that menisci do not act as a shock absorber in the knee, as was previously believed. To probe the relations between osmolarity and material properties, it was identified experimentally that meniscal samples swell significantly under iso-osmotic conditions. This swelling results in greatly altered mechanical properties in those samples. The osmolarity independent swelling indicates that the menisci are a pre-stressed structure.

For the first time, a novel imaging modality, optical projection tomography (OPT) was successfully used to examine connective tissue structure. With OPT, the highly complex, threedimensional collagen matrix organization within the meniscus was revealed. OPT was also capable of visualizing blood vessel organization in meniscal samples.

The localization of the matrix molecules, aggrecan, type II collagen, elastin and proteoglycan 4 were evaluated using various histological and immunofluorescence techniques. The localization was examined as it related to the various architectural subunits of the menisci to further elucidate the composition and organization of those regions. These techniques led to the identification of a new region in the menisci;​ a proteoglycan-rich, peri-vascular region. It is hypothesized that this region plays a protective role for blood vessels in the menisci. It was further identified that elastin has a region specific distribution which suggests a mechanical role for this protein in the menisci. Collagen II and aggrecan were observed to co-localize in the menisci, indicating similarities with other connective tissues that undergo compressive loading. Finally, these findings were integrated into a novel structural model of meniscal function, which proposes mechanical roles for each of the architectural sub-regions of the menisci.