Abstract:Articular cartilage is a layer of low-friction, load-bearing soft hydrated tissue covering articulating bony ends in diarthrodial joint. The vital mechanical function is maintained by the metabolism of chondrocytes, which is largely controlled by the physical factors such as joint loading. In this paper, studies on mechanical behaviors and theoretical modeling of articular cartilage and chondrocytes are reviewed with the particular emphasis on physical regulation of chondrocytes biosynthetic activities toward tissue maintenance, and its application in functional tissue engineering for cartilage repair and regenerative medicine. In this review article, first, the molecular composition and ultrastructure of articular cartilage and its tensile, compressive, and shear properties will be described, with their interrelationships emphasized. Then, the widely-used constitutive models, i.e., the biphasic and triphasic mixture theories, will be introduced to describe the tissues’ mechano-electrochemical behaviors, and with special emphasis on the recent advances toward the simplification of the complex triphasic theory described. Finally, mechanical properties, and theoretical modeling of chondrocytes and chondrons, are reviewed to enhance understanding of mechano-electrochemical signals around and in chondrocytes embedded within the extracellular matrix. In light of the mixture theories, the flow-dependent and flow- independent viscoelastic behaviors, swelling behaviors, and electrokinetic behaviors of articular cartilage have been successfully and theoretically described. The extension of mixture description to the chondrocytes and the surrounding pericellular matrix in the literature has also provided new insights in the physical regulatory mechanisms that influence cell behaviors in situ. In conclusion, with the powerful mixture theories, and new experimental techniques, novel and invariant approaches to investigate the chondrocyte-matrix interactions have been developed, with possible beneficial approaches toward successful engineering of artificial cartilage.