Theoretical and experimental studies were performed to address the relationships between the microstructure, composition, and mechanical behaviors of articular cartilage and hydrogel-based engineered constructs for functional tissue engineering of articular cartilage. The contributions of the two major components of articular cartilage — negatively charged proteoglycans and bimodular collagen fibrils — to electromechanical properties was described by a triphasic model (Lai, Hou et al, 1991) that is incorporated with conewise linear elasticity constitutive model (Cumier, He et al 1995). The model was solved analytically for the unconfined compression stress relaxation. The fixed charge density of the tissue was successfully quantitatively calculated from stress-relaxation experiments on whole tissue samples. The interaction between collagen and proteoglycans, and the resulting residual stress and curling behaviors of cartilage strips were analyzed with a layeredinhomogeneous, orthotropic, triphasic model. The predicted variation of the curvature with external saline concentration agreed with previous experimental data from our laboratory.

The implications of the charged nature of tissue, tension-compression nonlinearity (TCN), and the layered inhomogeneous structure on chondrocyte environment, especially the electrical potential and residual stresses and strains, were explored by rigorous theoretical modeling. This represents a necessary and crucial step toward the understanding of mechano-signals around chondrocytes in the native tissue and guides future biomimetic design of bioreactors for developing functional engineered cartilage equivalents.

Finally, the extracellular matrix deposition inside the hydrogel-based engineered constructs provides an alternative way to study the composition-function relationship. The variation of mechanical properties of chondrocyte-alginate constructs with incubation time, cell density, and the calcium concentration was analyzed with shear tests and a continuous-spectrum linear viscoelastic model. Our results suggested that torsional shear tests directly reveal the intrinsic properties of the solid matrix of these constructs, and provide one of the most effective and sensitive techniques for evaluating the quality of hydrogel-based engineered constructs.