Magnetic Hyperthermia–Synergistic H2O2 Self-Sufficient Catalytic Suppression of Osteosarcoma with Enhanced Bone-Regeneration Bioactivity by 3D-Printing Composite Scaffolds

Chemotherapy resistance and bone defects caused by surgical excision of osteosarcoma have been formidable challenges for clinical treatment. Although recently developed nanocatalysts based on Fenton-like reactions for catalytic therapy demonstrate high potential to eliminate chemotherapeutic-insensitive tumors, insufficient concentration of intrinsic hydrogen peroxide (H 2 O 2 ) and low intratumoral penetrability hinder their applications and therapeutic efficiency. The synchronous enriching intratumor H 2 O 2 amount or nanoagents and promoting osteogenesis are intriguing strategies to solve the dilemma in osteosarcoma therapy. Herein, a multifunctional “all-in-one” biomaterial platform is constructed by co-loading calcium peroxide (CaO 2 ) and iron oxide (Fe 3 O 4 ) nanoparticles into a three-dimensional (3D) printing akermanite scaffold (AKT-Fe 3 O 4 -CaO 2 ). The loaded CaO 2 nanoparticles act as H 2 O 2 sources to achieve H 2 O 2 self-sufficient nanocatalytic osteosarcoma therapy as catalyzed by coloaded Fe 3 O 4 nanoagents, as well as provide calcium ion (Ca 2+ ) pools to enhance bone regeneration. The synergistic osteosarcoma-therapeutic effect is achieved from both magnetic hyperthermia as-enabled by Fe 3 O 4 nanoparticles under alternative magnetic fields and hyperthermia-enhanced Fenton-like nanocatalytic reaction for producing highly toxic hydroxyl radicals. Importantly, the constructed 3D AKT-Fe 3 O 4 -CaO 2 composite scaffolds are featured with favorable bone-regeneration activity, providing a worthy base and positive enlightenment for future osteosarcoma treatment with bone defects by the multifunctional biomaterial platforms.