Calcium sulfate-magnesium oxide composites for antimicrobial and pro-osteogenic bone grafting materials

• This study successfully developed calcium sulfate (CaS)–magnesium oxide composites, which exhibit significant antibacterial properties and osteogenic potential. • The composites effectively inhibit bacterial growth and biofilm formation through the generation of reactive oxygen species, achieving antibacterial and anti-fungal activity and significantly reducing pre-formed biofilms. • In osteogenic induction, the CaS-2.5MgO group demonstrated the highest alkaline phosphatase activity and mineralized nodule formation, indicating its superior osteogenic effects. • In vivo experiments further confirmed the antibacterial efficacy and good biocompatibility of these composites, providing a novel bone graft material with dual functions of antibacterial and osteogenic activities for bone defect repair. Calcium sulfate (CaS) is a commonly used synthetic bone graft material, but it lacks antimicrobial properties. Magnesium oxide (MgO) has been reported to possess antimicrobial and osteogenic effects in vitro . The present study aimed to develop and evaluate MgO-CaS composites for their antimicrobial and biological properties. MgO nanoparticles were mixed with α-calcium sulfate hemihydrate at 0–25% (w/w). The resultant composites were characterized for setting time, compressive strength, degradation, pH change, and reactive oxygen species (ROS) generation. In vitro inhibition of three pathogens ( E. coli , S. aureus , C. alb .), disruption of bacterial biofilm formation, biocompatibility, alkaline phosphatase (ALP) expression, and angiogenic potential were studied. In vivo antibacterial ( S. aureus ) effects were also evaluated in a rat muscle model. The addition of MgO shortened the setting time and reduced compressive strength. In vitro , the composites exhibited a stable pH plateau and nearly linear degradation profiles; they inhibited bacterial biofilm formation by 18.1–62.0% and reduced the masses of pre-formed biofilms by 31.7–86.5%; they also reduced the formation of bacterial colonies by 87.5–99.0% and fungal colonies by 81.6–97.9%. In vitro biocompatibility decreased with increasing MgO content, but composites with 0–7.5% MgO were non-cytotoxic. ALP levels and angiogenic potential peaked at 2.5% and 7.5% MgO, respectively. In vivo , the composites significantly reduced the retrieved bacterial counts and white blood cell infiltration compared with CaS. These suggest that CaS-MgO composites are effective antimicrobial bone grafting materials with reasonable biocompatibility and potential to reduce infection rates.