Dual-Functional Interface Engineering of Mesoporous Bioactive Glass via Polydopamine Chelation for 3D-Printed Scaffolds with Synergistic Photothermal Therapy and Enhanced Osteogenesis

Osteosarcoma resection creates critical-sized bone defects plagued by residual tumor cells and compromised regeneration due to chemo-radiotherapy toxicity. While 3D-printed scaffolds offer anatomical precision, multifunctional implants enabling concurrent tumor ablation and vascularized bone repair remain an unmet need. Here, we engineered a tritherapeutic platform by functionalizing mesoporous bioactive glass (MBG) with polydopamine (PDA) for photothermal tumor eradication under NIR irradiation (808 nm), followed by Mg²⁺ chelation (MBG@PM) to confer pro-angiogenic activity. The resulting MBG@PM nanoparticles were incorporated into chitosan (CS) bioinks for cryogenic 3D printing, fabricating patient-specific MBG@PM-CS scaffolds. These constructs demonstrated exceptional photothermal capacity and tumor elimination in vitro/vivo. Sustained release of Mg²⁺/Ca²⁺/Si⁴⁺ ions from MBG@PM synergistically stimulated angiogenesis and osteogenesis. In rat critical-sized femoral defects, MBG@PM-CS scaffolds accelerated coupled vascularization and bone regeneration, achieving enhanced defect healing at 8 weeks via microcomputed tomography (Micro-CT) and histological analysis. This platform introduces a tripartite strategy enabling concurrent tumor ablation, osteo-angiogenic coupling, and structural bone restoration, providing a promising approach for the treatment of osteosarcoma.