Influence of chondrocyte maturation on acute response to impact injury in PEG hydrogels

Abstract

Age is a risk factor in developing osteoarthritis, but the link is not well understood. It is thought that age predisposes the tissue to osteoarthritis when other risk factors are involved, e.g. abnormal biomechanics. Therefore, this study aimed to test the hypothesis that chondrocyte response to injurious loading is dependent on donor age. Bovine chondrocytes were selected as model cells and isolated from skeletally immature (juvenile, 1-3 weeks) or mature (adult, 2-3 years) cartilage to represent different aged donors. Juvenile and adult chondrocytes were encapsulated in identical 3D poly(ethylene glycol) hydrogels and subjected to an initial compressive impact load of 25.6±7.5 kN/m(2) applied to 50% strain. Under free swelling culture, adult chondrocytes exhibited higher intracellular ROS levels and catabolism, specifically collagen degradation, when compared to juvenile chondrocytes. In response to injurious load, adult chondrocytes responded with higher cell death, while juvenile chondrocytes responded with greater apoptosis and greater increases in intracellular ROS. With respect to anabolism and catabolism in response to injurious load, adult chondrocytes exhibited decreased aggrecan and collagen deposition, while juvenile chondrocytes exhibited decreased proteoglycan synthesis and increased collagen degradation. Overall, chondrocytes responded to injury regardless of age, but exhibited age-dependent responses with respect to anabolism and catabolism. These findings confirm that age influences how chondrocytes respond to abnormal biomechanical cues, warranting further study into the mechanisms of how cells, age, and injury contribute to the onset of osteoarthritis.