NIR-II-activated supramolecular LDH nanoarchitecture integrated with 3D-printed bioactive glass for hypoxia-resistant photodynamic osteosarcoma therapy and bone regeneration

The clinical management of osteosarcoma faces critical challenges, including postoperative recurrence and metastasis of residual tumor cells, chemotherapy resistance, and impaired self-repair capacity due to extensive bone defects following tumor resection. Herein, we develop a novel functionalized 3D-printed scaffold with NIR-II responsiveness (BGS/I-LDH@MgO 2 ), designed to simultaneously address the dual needs of inhibiting osteosarcoma recurrence and promoting bone regeneration. This scaffold consists of 3D-printed bioactive glass scaffold (BGS) and MgO 2 -modified ZnAl-layered double hydroxides (ZnAl-LDHs) intercalated with 5-iodo-isophthalic acid (I-IPA). Under NIR-II irradiation, the scaffold effectively triggers a photodynamic therapy (PDT) effect to eliminate osteosarcoma cells. Notably, the incorporation of MgO 2 enables oxygen release within the tumor microenvironment, alleviating hypoxia and enhancing PDT efficacy for superior antitumor performance. Furthermore, the degradation of ZnAl-LDHs and MgO 2 releases Mg 2+ and Zn 2+ ions and generates a mildly alkaline microenvironment, which collectively facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate the process of bone healing. This functionalized 3D-printed scaffold demonstrates excellent anti-tumor and osteogenic properties, showing great promise for the treatment of osteosarcoma-associated bone defects.