Evaluation of Novel Gallium Doped Bioactive Glass for the Management of Osteosarcoma

Abstract

Osteosarcoma is the most common primary malignant bone tumour in adolescents and young adults, often requiring aggressive treatment that includes surgery and chemotherapy. Despite advances in clinical management, challenges such as chemoresistance, tumour recurrence, and implant-associated infections persist. This research focuses on the development and characterisation of gallium-doped bioactive glasses (Ga-BGs) as a multifunctional material capable of both anticancer and antimicrobial activity, while supporting bone regeneration. A series of Ga-BGs were synthesised by incorporating varying molar percentages of Ga₂O₃ into the 45S5 bioactive glass system (0-5 mol% Ga). The glasses were evaluated for their physicochemical properties, ion release profiles, and biological performance. The cytotoxic effects of Ga-BG conditioned media were investigated using osteosarcoma (OS) cell lines (Saos-2, HOS and U2-OS) and normal human osteoblast as well as healthy human mesenchymal stem cells. Results from MTT and Live/Dead assays revealed a selective cytotoxic effect on OS cells, with minimal impact on healthy cells. Flow cytometry confirmed elevated transferrin receptor (TfR) expression in OS cells, supporting gallium’s targeted action through iron-mimicking mechanisms. Caspase-3/7 activation assays further demonstrated the induction of apoptosis in cancer cells following exposure to Ga-doped media. In parallel, the antibacterial activity of Ga-BGs was investigated against E. coli and S. aureus using viability assays, time-kill studies, and fluorescence microscopy. The materials exhibited dose-dependent bactericidal activity, in particular against E. coli, highlighting their potential in preventing implant-associated infections.