The knee menisci are a pair of wedge-shaped tissues that sit in between the tibia and the femur and are crucial to maintaining knee function. Due to its overall shape and position within the knee joint, the meniscus experiences a wide range of mechanical loads and exhibits heterogeneous properties, which has many implications for meniscal degradation. Effective detection and treatment of meniscal degeneration can be critical in preventing osteoarthritis as meniscal degeneration often precedes that of cartilage and is a high risk factor for the disease. Efforts to improve detection and treatment strategies would be substantially enhanced by quantitative information describing varying characteristics of meniscal regions, as different regions may respond differently during disease progression and treatment. However, existing diagnosis methods provide little or no ability to non-invasively detect such meniscal heterogeneity in the tissue matrix;​ only gross morphological changes such as tears and extrusions are detectable and treated. In addition, the lack of quantitative information on meniscal heterogeneity hinders the development an effective, long-term solution that can treat degeneration in the meniscus and prevent osteoarthritis. The purpose of this dissertation was thus to find quantitative characteristics that defined meniscal heterogeneity and to evaluate non-invasive diagnostic methods that could reflect the matrix tissue properties and detect meniscal heterogeneity.

In the first part of this work, gene expression profiles of meniscal cells were used to identify quantitative markers that could distinguish between different regions of the meniscus, describing its heterogeneous properties. This information was then applied in evaluating cell sources for tissue engineering strategies, contributing to developing an effective treatment for meniscal degeneration. First, expression levels of genes important to matrix production and regulation were measured and gene expression ratios that showed distinct levels among the inner, middle and outer regions of the meniscus were selected using statistical methods. These gene expression ratios revealed a spectrum of cell phenotypes from the inner to the outer meniscal cell and were applied to evaluate passaged cartilage and meniscus cells as potential sources for meniscal tissue engineering. Two metrics were additionally defined to quantify the effect of passaging and subsequent 3D culture on the cell phenotypes in adult and juvenile cartilage and meniscus cells. In general, regardless of age or tissue of origin, the cells progressed towards the cell phenotype of an outer meniscal cell with passage, and 3D culture did not have a great effect on reversing this trend.

The second part of the dissertation was motivated by the goal of detecting meniscal tissue properties that reflect meniscal heterogeneity in a non-invasive manner. Ultimately, such information would be useful in identifying internal degenerative changes that take place in the matrix of the tissue prior to macroscopic injuries. In this section, the relationship between magnetic resonance imaging parameters and various meniscal tissue properties were examined. T1ρ and T2 relaxation times for different regions in degenerate human menisci were measured and correlated with the biochemical composition and mechanical properties of the tissue. Both T1ρ and T2 relaxation times were highly sensitive to water, which seemed to dominate the effects of other matrix compositions. The high correlation between the two imaging parameters indicated that only one might be necessary as a diagnostic tool in a clinical setting. In addition, an exploratory aim visualized the internal secondary collagen network in the meniscus and examined its deformation in different mechanical loading positions.

This work significantly adds to the understanding of the heterogeneous properties of the meniscus and the potential of magnetic resonance imaging parameters as detection markers. It contributes to the advancement of diagnosis and treatment strategies for meniscal degeneration, which has further implications for preventing osteoarthritis progression.