Injectable and adhesive MgO2-potentiated hydrogel with sequential tumor synergistic therapy and osteogenesis for challenging postsurgical osteosarcoma treatment

The clinical treatment of osteosarcoma faces great challenges of residual tumor cells leading to tumor recurrence and irregular bone defects difficult to repair after surgery removal of the primary tumor tissue. We developed an injectable and in-situ cross-linkable hydrogel (named MOG hydrogel) using MgO2 nanoparticles and dopamine- conjugated gelatin as main components. MgO2 was rationally designed as a multifunctional active ingredient to mediate in situ gelation, tumor therapy, and bone repair sequentially. The 10MOG (with 10 mg/mL MgO2 content) showed excellent gel stability, injectability, shape adaptability, tissue adhesion, and rapid hemostatic ability. Importantly, 10MOG exhibited ideal sequential H2O2 and Mg2+ release property. The released H2O2 synergized with photothermal therapy for enhanced tumor recurrence suppression, and the sustainable Mg2+ release efficiently promoted bone regeneration. The MOG hydrogel, possessing excellent on-demand antitumor and osteogenic capabilities in vitro and in vivo, exhibited tremendous potential in the clinical application for challenging postsurgical osteosarcoma treatment.