Mixed-valence vanadium-doped mesoporous bioactive glass for treatment of tumor-associated bone defects

Abstract

Vanadium is a bioactive trace element with variable valence. Its pentavalent form has been confirmed to be capable of predominantly regulating the early and mid-stage osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without tumor inhibition, while its tetravalent form exhibits tumor inhibition but only primarily modulates late osteogenic differentiation and angiogenesis. In this study, a multifunctional bone tissue scaffold consisting of mixed-valence vanadium-doped mesoporous bioactive glass and poly(lactic-co-glycolic acid) (V(IV/V)-MBG/PLGA) was developed to simultaneously inhibit the recurrence of osteosarcoma and promote the regeneration of operative bone defects. The in vitro results showed that the V(IV) and V(V) species could be sustainably released from V(IV/V)-MBG and complementarily enhance the proliferation, osteogenic differentiation, and mineralization of BMSCs by activating multiple signaling pathways throughout the whole osteogenesis process. More importantly, the co-existence of mixed-valent vanadium species was able to continuously stimulate the generation of excessive ROS and the depletion of GSH by synergistically supplying an appropriate ratio of V(IV) and V(V) to thermodynamically and kinetically maintain the stable self-circulation of the valence state alteration, thus inducing UMR-106 cell death. In a rat model, V(IV/V)-MBG/PLGA scaffolds effectively suppressed tumor invasion and promoted bone regeneration. These results suggest that V(IV/V)-MBG/PLGA scaffolds are a promising strategy for treating tumor-associated bone defects, offering dual tumor inhibition and bone regeneration.