Osteosarcoma (OS) is a primary bone malignant tumor. The current clinical standard treatment for OS comprises a combination of neoadjuvant chemotherapy and surgical resection. However, the clinical postsurgical treatment faces challenges in the staged therapeutic requirements of early anti-tumor, anti-bacterial, and long-lasting osteogenesis. 

Recently, a research team led by Prof. LAI Yuxiao and Prof. QIN Ling from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences developed multi-functional bioactive scaffolds with time-sequential functions of preventing tumor recurrence, inhibiting bacterial infection, and promoting bone defect repair. The study was published in Advanced Materials. 

The researchers designed MgO₂ as the multi-functional component to fabricate polymeric composite bone scaffolds as the depot of H₂O₂ and Mg²⁺. To realize the sequential release of H₂O₂ and Mg²⁺ to exert multiple functions, they employed low-temperature rapid prototyping (LT-RP) 3D printing technology to fabricate MgO₂-embedded poly (lactide-co-glycolide) (MgO₂/PLGA) composite scaffolds with hierarchical pore structures. 

The researchers found that MgO₂/PLGA scaffolds with 20 wt% MgO₂ (20MP) has desired mechanical properties, and exhibits staged release behavior of bioactive elements with hydrogen peroxide (H₂O₂) release for the first three weeks, and long-lasting Mg²⁺ release for 12 weeks. 

The 20MP scaffold was demonstrated to exert multiple functions in a time-sequential manner. In the first stage, the released H₂O₂ efficiently inhibited bacterial infection and suppressed tumor recurrence through chemodynamic therapy-mediated cancer apoptosis and ferroptosis, along with activating anticancer immune microenvironment by M1 polarization of macrophages. In the second stage, the released Mg²⁺ could efficiently promote differentiation and mineralization of bone marrow mesenchymal stem cells by activating Wnt signaling pathway and creating osteopromotive immune microenvironment by M2 polarization of macrophages.  

The experiments on OS postsurgical recurrence mouse model and bone defect rat model in vivo showed that the as-designed MgO₂/PLGA composite scaffolds exhibited excellent anti-tumor, antibacterial, and osteogenic activities.  

"Our strategy has great potential for clinical applications in postsurgical OS treatment," said Prof. LAI.