Injectable Hydrogels Composed of Thiolated Chitosan, Silk Fibroin, and Gallium-Doped Bioactive Glass Nanoparticles for Bone Regeneration and Osteosarcoma Suppression

Purpose: The repair and reconstruction of bone defects resulting from tumor-related bone resection surgery face significant challenges. Developing biomaterials with dual functions of tumor therapy and bone regeneration is a promising strategy for osteosarcoma treatment. Methods and Results: In this study, gallium-doped bioactive glass nanoparticles (GaBG NPs) with Ga contents of 5-15 mol% were synthesize and integrated into thiolated chitosan (CS-NAC) and silk fibroin (SF) composites to fabricate hydrogels systems for post-surgical bone repair applications. The optimized hydrogel system exhibited good injectability with a gelation time of approximately 4 min, moderate mechanical strength (> 3 kPa), high porosity, and sustained release of Si, Ca, and Ga ions within physiologically safe levels. In vitro, studies demonstrated that the GaBG-embedded hydrogels remarkably advanced the proliferation and osteogenic differentiation of MC3T3-E1 cells, while significantly inhibiting the growth of UMR-106 osteosarcoma cells, with the 15GaBG/CNS hydrogel reducing cell viability to