Osteosarcoma is an aggressive primary bone malignancy associated with high recurrence rates and limited therapeutic outcomes, necessitating the development of biomaterials capable of supporting bone regeneration while modulating tumor cell response. Our study focuses on the fabrication of Mg–Zn co-doped hydroxyapatite (M-HAp) and its incorporation to form composites, using poly lactic acid (M-HAp-PLA) and a ternary nanocomposite with nanotubular reinforcement (M-HAp-PLA-HNT). The composites were investigated in vitro for their toxicity and anti-cancer activity using L929 (mouse fibroblast cell) and MG-63 (human osteosarcoma cells). Cell viability assessed by the MTT assay confirmed that all composites maintained >90% viability, indicating acceptable selective cytocompatibility. ROS and AO/PI supported MTT assay with viable cells observed after treatment, the composites where AO/PI staining showed predominantly viable (green) cells with a limited fraction of membrane-compromised (red) cells, indicating partial but controlled cellular stress. DAPI staining further confirmed intact nuclear morphology, with no evident chromatin condensation or fragmentation. The observed biological response suggests that the combined effects of Mg2+ and Zn2+ ionic substitution, along with polymeric (PLA) and nanotubular (HNT) reinforcement, contribute to enhanced surface reactivity and regulated cell–material interactions. In particular, the ternary nanocomposite system exhibits a more uniform cellular distribution with moderated oxidative stress, without inducing extensive cytotoxic damage. Substantially, the developed composites exhibit a balanced dual functionality, combining cytocompatibility with controlled anticancer activity and demonstrate potential as advanced biomaterials for post-resection osteosarcoma management and bone tissue engineering applications.
Sivakumar et al. (2026) studied this question.