Regulation of the Viscoelastic Properties of Hyaluronate–Alginate Hybrid Hydrogel as an Injectable for Chondrocyte Delivery

[Image: see text] Modulation of the viscoelastic properties of hydrogels is critical in tissue engineering applications. In the present study, a hyaluronate–alginate hybrid (HAH) was synthesized by introducing alginate to the hyaluronate backbone with varying molecular weights (700–2500 kDa), and HAH hydrogels were prepared in the presence of calcium ions at the same cross-linking density. The storage shear moduli of the HAH hydrogels increased with the concomitant increase in the molecular weight of hyaluronate in the HAH polymer. The HAH hydrogels were also modified with arginine–glycine–aspartic acid (RGD) and histidine–alanine–valine (HAV) peptides to enhance cell–matrix and cell–cell interactions, respectively. The chondrogenic differentiation of ATDC5 cells encapsulated within the HAH hydrogels was enhanced with the increase in the storage shear moduli of the gels in vitro as well as in vivo. This approach of regulating the viscoelastic properties of hydrogels using polymers of varying molecular weights at the same cross-linking density may prove to be useful in various tissue engineering applications including cartilage regeneration.