3D Molybdenum Disulfide Nanospheres Loaded with Metformin to Enhance SCPP Scaffolds for Bone Regeneration

Conventional strontium-doped calcium polyphosphate (SCPP) ceramics have attracted a lot of attention due to good cytocompatibility and controlled degradation. However, their poor mechanical strength, brittleness, and difficulty in eliminating unavoidable postoperative inflammation and bacterial infections in practical applications limit their further clinical application. In this study, carboxylated molybdenum disulfide nanospheres (MoS₂-COOH) were first prepared via a one-step hydrothermal method. The optimal doping concentration of MoS₂-COOH was then incorporated into SCPP to overcome its poor mechanical strength. To further enhance the anti-inflammatory properties of scaffolds, metformin (MET) was loaded onto MoS₂-COOH through covalent bond cross-linking (MoS₂-MET). Then MoS₂-MET was doped into SCPP (SCPP/MoS₂-MET) according to the previously obtained concentration, resulting in the controlled and sustained release of MET from the SCPP/MoS₂-MET scaffolds for 21 days in vitro. The SCPP/MoS₂-MET scaffolds were shown to have good biological activity in vitro to promote stem cell proliferation and the potential to promote mineralization in vitro. It also showed good osteoimmunomodulatory activity could reduce the expression of proinflammatory factors and effectively induce the differentiation of BMSCs under inflammatory conditions, upregulating the expression of relevant osteoblastic cytokines. In addition, SCPP/MoS₂-MET scaffolds could effectively inhibit Staphylococcus aureus and Escherichia coli. In vivo experiments also demonstrated better osteogenic potential of SCPP/MoS₂-MET scaffolds compared with the other scaffold-samples. Thus, the introduction of carboxylated molybdenum disulfide nanospheres is a promising approach to improve the properties of SCPP and may provide a new modification strategy for inert ceramic scaffolds and the construction of multifunctional composite scaffolds for bone tissue engineering.