Hyaluronate-alginate hybrid hydrogels prepared with various linkers for chondrocyte encapsulation

•Hyaluronate-alginate hybrid (HAH) can be synthesized using various linkers.•The types of linkers control the mechanical stiffness of HAH hydrogels.•The mechanical stiffness of HAH hydrogel regulates chondrogenic differentiation. Tissue engineering typically requires a use of scaffolds when delivering tissue-specific cells to be engineered. Hydrogels are frequently used as scaffolds, because their composition, structure, and function resemble the natural tissue extracellular matrix. In this study, hyaluronate-alginate hybrid (HAH) was synthesized by conjugating alginate (ALG) with the hyaluronate (HA) backbone using various types of linkers. HAH hydrogel was prepared by physically cross-linking the HAH polymer in the presence of calcium ions without chemical cross-linkers. The mechanical stiffness of HAH hydrogel was significantly affected by changing the type of a linker between HA and ALG. The mechanical stiffness increased with increasing linker length, likely due to enhanced intermolecular reactions between HA and ALG. This enables controlling the mechanical properties of HAH hydrogels. The types of linkers used to synthesize HAHs also influenced the chondrogenic differentiation of ATDC5 cells cultured in HAH hydrogel in vitro. This hybrid system that can change the mechanical stiffness by varying the linker type while maintaining the cross-linking density may be useful to design and fabricate scaffolds for tissue engineering applications, including cartilage regeneration.