3D printed magnesium-doped β-TCP gyroid scaffold with osteogenesis, angiogenesis, immunomodulation properties and bone regeneration capability in vivo

Bioceramics have been used in orthopedic surgery for several years. Magnesium (Mg) is an essential element in bone tissue and plays an important role in bone metabolism. Mg-doped bioceramics has attracted the attention of researchers recently. However, the optimal doping amount of Mg in β-TCP and the immunomodulatory property of Mg-doped β-TCP (Mg-TCP) have not been determined yet. In this study, β-TCP scaffolds doped with different contents of magnesium oxide (0 wt%, 1 wt%, 3 wt%, and 5 wt%) with gyroid structure were printed by digital light processing (DLP) method, and the physicochemical and biological functions were then investigated. Mg-doping improved the physicochemical properties of the β-TCP scaffolds. In vitro experiments confirmed that the doping of Mg in β-TCP scaffolds promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenic differentiation of endothelial progenitor cells (EPCs), where the 5Mg-TCP has the optimal properties when using the "one cell type" method. It was also found that all Mg-TCP facilitated the polarization of RAW264.7 cells to the M2 phenotype, especially the 3Mg-TCP. However, 3Mg-TCP displayed the optimal osteogenic and angiogenic potential when using a "multiple cell type" method, which referred to culturing the BMSCs or EPCs in the macrophage-conditioned medium. Finally, the in vivo experiments were conducted and the results confirmed that the 3Mg-TCP scaffolds possessed the satisfying bone defect repair capability both after 6 and 12 weeks of implantation. This study suggests that 3Mg-TCP scaffolds provide the optimal biological performance and thus have the potential for clinical translation.