Design of a compression bioreactor for the mechanical stimulation of native and artificial cartilage and the study of the kinetics of enzymatic degradation of collagen fibrils in loaded cartilage

Approximately 85 billion dollars is spent annually on medical expenses related to articular cartilage damage as a result of osteoarthritis (OA), a disease of unknown etiology affecting more than 21 million Americans. Articular cartilage is a highly specialized, load bearing tissue that allows frictionless movement and even force distribution across the joints. These properties are a function of the extracellular matrix, which makes up more than 90% of cartilage tissue volume and primarily consists of collagen, proteoglycans and water. But articular cartilage is an avascular tissue with limited ability for effective self repair, leading to deterioration and loss of function after injury. Current research aims to develop artificial cartilage and find a suitable replacement for worn tissue. Studies have shown that mechanical stimulation significantly improves matrix deposition and the resulting mechanical properties of cartilage constructs. This research study aims to better understand the in-vivo catabolic and anabolic mechanism of cartilage, a vital consideration in the design of a suitable replacement.;A major part of this project has been to design and fabricate a novel compression bioreactor for cartilage tissue engineering. The bioreactor was designed to apply mechanical stimulation at different frequencies and amplitude under human physiological conditions, with potential to improve the mechanical properties of engineered tissue. The bioreactor can simultaneously run five different experiments with continuous data collection from each of the five wells through separate load cells. The overall cost was almost four times less than that of a similar commercially available device.;Another goal of this study has been to investigate the kinetics of enzymatic degradation of collagen in loaded cartilage. In OA, the degradation of collagen fibrils by matrix metalloproteinases is thought to be responsible for general mechanical deterioration. The bioreactor has been utilized to investigate the effect of excessive compressive loading on enzymatic cleavage of cartilage collagen, a feasible cause of OA. We hypothesize that in OA, collagen fibrils buckle under excessive compressive load increasing their susceptibility to enzymatic cleavage. Such a model could account for the observed positive feedback cycle, where loss of PGs leads to further losses of both collagen and PGs.