Engineering the Cell Environment for Meniscus Repair

The menisci are fibrocartilaginous tissues of the knee that specialize in load-bearing and stabilization of the joint. Though once believed to be "the functionless remains of leg muscles," and therefore routinely removed after injury, it is now understood that loss of meniscus integrity leads directly to degenerative changes in the knee, inspiring new pursuits to overcome the intrinsic limitations to meniscus repair. However, many components of the meniscus environment and their roles in regulating the cellular response of injured tissue remain unclear. This thesis presents novel strategies to enhance integrative repair of the meniscus, via control of the cell environment from the micro- to macro-scale. The unifying hypothesis of this dissertation was that the application of chemical, physical, and environmental factors can significantly influence the meniscus cell environment and contribute to healing. Specifically, we studied the direct role of vasculature on the meniscus, and identified angiogenic factors that regulate cell migration and tissue repair between the inner and outer regions. We analyzed the effects of pulsatile direct current electrical stimulation on meniscus cell migration and repair, and describe the mechanisms of electrotransduction in the meniscus. Finally, we developed a decellularized meniscus extracellular matrix hydrogel to deliver and dictate the behavior of stem cells for meniscal repair. By rigorous study of each element at the micro-scale and integration at the macro-scale, novel therapies for meniscus repair will emerge towards clinical applications.