Finding the Links between Knee Injuries and Osteoarthritis

Abstract

The knee joint is one of the most complex organs in our bodies, and is one the most susceptible to injury. Traumatic injuries to the knee joint can cause pain, instability, and misalignment; altering joint loading patterns, which in turn can cause a cascade of events that leads to the development of osteoarthritis. Much research has been dedicated to understanding the onset and development of this disease using mechanical devices to apply uniaxial loads on 3D chondrocyte (cartilage cells) seeded in hydrogel culture models. However, these loads do not simulate complex loading similar to physiological loading. Therefore, we have developed the first precise multiaxial-loading device that can apply complex loading to an in vitro hydrogel model (Figure 1). Our model was validated by determining the strain distribution of dynamic loads through different zones of our hydrogel construct, which was also correlated with changes in cellular-shape, and angle of rotation of the cells to improve our understanding of how mechanical loads affect chondrocytes. Finally, changes in the expression of genes important in cartilage matrix remodelling were measured using real-time PCR to determine the effects of applying different loading modes (compression, tension, shear, and complex loading which was a combination of the three modes) on chondrocyte mechanobiology, using our device. Two loading regimes, intermittent and continuous were used to mimic physiological and injurious. We found that complex loading regimes promoted cartilage homeostasis, similar to the behaviour of in vivo chondrocytes; while continuous loading increased induced degradative enzyme activity, similar to trends found in explant and clinical studies following knee injury. The system developed in this research is the device best capable of fully mimicking in vivo conditions in health and disease. Work here has significantly enhanced our knowledge of chondrocyte mechanobiology, ultimately working towards understanding the development of osteoarthritis.