A Gelatin-Hyaluronic Acid Double Cross-Linked Hydrogel for Regulating the Growth and Dual Dimensional Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells

Owing to its unique physiochemical properties similar to the extracellular matrix (ECM), three-dimensional (3D) crosslinked hydrogels are widely studied materials for tissue engineering. In this study, to mimic the ECM microenvironment, a two-step covalent cross-linking with hyaluronic acid and gelatin was performed to form an interpenetrating polymer network structure. Gelatin as the first network greatly improved the mechanical strength of the hydrogels, while a hyaluronic acid network as the second network improved the tenacity and biological activity. Compared with a single network hydrogel, the interpenetrating hydrogel system can further regulate the mechanical properties of the hydrogel by adjusting the ratio of the two components, thereby changing the proliferation, activity, and direction of cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). Not only that, with two culture methods for BMSCs on the surface and 3D wrapped in the double cross-linked hydrogels, they exhibited their potential to induce BMSCs to cartilage differentiation under the condition of 3D encapsulation of BMSCs and contact with BMSCs on its surface. As a scaffold material for cartilage tissue engineering, this double cross-linked hydrogel demonstrated its high feasibility and applicability in delivering BMSCs in vivo and repairing defects.