3D‐Printed Biomimetic Ceramic Scaffolds with Photothermal/Chemodynamic Effects and Ionic Microenvironment for Preventing Tumor Recurrence and Promoting Vascularized Bone Reconstruction

Abstract Osteosarcoma is an aggressive malignant bone tumor predominantly affecting adolescents and young adults, characterized by a high mortality rate. A significant challenge in treatment is the presence of residual tumor cells and associated bone defects. Here, a novel functionalized biomimetic ceramic scaffold is presented, which combines photothermal and chemodynamic therapies to effectively target bone tumors while promoting vascularized bone regeneration through an optimized ionic microenvironment. The scaffold consists of a 3D‐printed zinc‐doped β‐tricalcium phosphate ceramic matrix and a biomimetic dopamine‐modified hyaluronic acid hydrogel membrane loaded with Ti 3 C 2 MXene and iron ions. In the tumor microenvironment, the hydrogel membrane degrades rapidly, releasing iron ions that lead to glutathione depletion and downregulation of glutathione peroxidase 4. When exposed to near‐infrared light, Ti 3 C 2 enhances local temperature and catalyzes the redox cycling of iron ions, leading to the generation of hydroxyl radicals through Fenton reactions. This process results in lipid peroxidation and induces ferroptosis of tumor cells. Following the clearance of residual tumor cells, the gradual release of iron and zinc ions encourages osteogenic differentiation and vascularization, facilitating vascularized bone regeneration. Therefore, the biomimetic ceramic scaffold exhibits effective anti‐osteosarcoma properties while supports bone repair, presenting a promising treatment option for osteosarcoma‐associated bone defects.