Osteoarthritis (OA) is the leading cause of disability, worldwide. OA leads to breakdown of the articular cartilage (AC), the highly structured tissue that lines the end of bones of the synovial joints. The cartilage cells synthesize and maintain the homeostasis of articular cartilage, a function that is largely influenced by mechanical forces.Mechanobiological studies of cartilage are conducted toward a better understanding of osteoarthritis pathological mechanism. However, the typically applied loading protocols omit the relative surface motion that is essential for cartilage tribological function. Therefore, this work aimed to examine the effects of a more physiological loading mode on cartilage mechanobiological function.Finite element analysis (FEA) was performed to investigate the biomechanical response of cartilage to loading regimes that permits migrating contact area compared to uniaxial cyclic compression. Interstitial fluid pressure was maintained high under sliding contact while it reduced by 20% in cyclic compression model. Also, maximum fluid flow was reduced by 44% in uniaxial cyclic compression where fluid imbibition was limited to a small region near the lateral periphery. Cartilage surface curvature may contribute to cartilage mechanobiological function by increasing tissue rehydration.Motivated by FE results, two low-cost mechanical testing devices were designed and constructed to allow for in vitro mechanobiological experimentation of cartilage. Healthy and degenerated human cartilage samples were subjected to two types of intermittent loading, load-controlled sliding and displacementcontrolled unconfined cyclic compression. Changes in biochemical signals that are believed to control chondrocytes functionality were measured. The level of growth factor (TGF-β) was significantly higher in specimen subjected to sliding contact compared to cyclic compression. Also, the level of all measured cytokines ii First and for most, I would like to express my sincere appreciation for Prof. Andrew Speirs, who guided me step by a step through this work over the past five years. Without the support and guidance of Prof. Speirs, this work would not be possible. Thank you.