Copper-infused 13–93 bioactive glass inhibiting postoperative osteosarcoma recurrence and enhancing bone regeneration

Abstract

Osteosarcoma (OS)-induced bone abnormalities present a considerable clinical challenge due to elevated chances of recurrence and compromised repair, which significantly jeopardize patient survival. Contemporary bioactive glasses (BGs), notwithstanding their osteogenic potential, exhibit restricted anticancer efficacy. Therefore, It is essential to enhance the tumor-killing efficacy of BGs for usage as a filler in tumor-induced bone defects. Here, a copper (Cu)-doped 13–93BG (13–93BG-Cu) was synthesized and subsequently combined with chitosan to form the 13–93BG-Cu system. The rapid release of Cu ions (Cu^2 +) during the initial stages of this system enhances the killing of tumor cells by cuproptosis, as intracellular Cu²⁺ accumulation triggers the oxidative stress response within mitochondria, hence achieving anti-OS therapy. Subsequently, the sustained low-level release of Cu²⁺ and bioactive ions collaboratively influences the activation and function of macrophage and stem cells, promoting bone defect healing. This study introduces a dual-action BG that simultaneously neutralizes the acidic tumor microenvironment and promotes cuproptosis, effectively preventing recurrence while facilitating bone healing via Cu²⁺ gradient release.