Matrix Deposition Modulates the Viscoelastic Shear Properties of Hydrogel-Based Cartilage Grafts

Hydrogel-based scaffolds such as alginate have been extensively investigated for cartilage tissue engineering, largely due to their biocompatibility, ambient gelling conditions, and the ability to support chondrocyte phenotype. While it is well established that the viscoelastic response of articular cartilage is essential for articulation and load bearing, the time-dependent mechanical properties of hydrogel-based cartilage scaffolds have not been extensively studied. Therefore, the objective of this study was to characterize the intrinsic viscoelastic shear properties of chondrocyte-laden alginate scaffolds and determine the effects of seeding density and culturing time on these properties. Specifically, the viscoelastic properties (equilibrium and dynamic shear moduli and dynamic phase shift angle) of these engineered cartilage grafts were measured under torsional shear. In addition, the rapid ramp-step shear stress relaxation of the alginate-based cartilage scaffolds was modeled using the quasi-linear viscoelastic (QLV) theory. It was found that scaffold stiffness increased with both culturing time and cell density, whereas viscosity did not change significantly with cell density (30 vs. 60 million/mL). Similar to native cartilage, the energy dissipation of engineered scaffolds under pure shear is highly correlated to the glycosaminoglycan content. In contrast, collagen content was not strongly correlated to scaffold shear modulus, especially the instantaneous shear modulus predicted by the quasi-linear viscoelastic model. The findings of this study provide new insights into the structure-function relationship of engineered cartilage and design of functional grafts for cartilage repair.