Pathogen persistence, inflammation resolution, and bone repair in Staphylococcus aureus osteomyelitis

Staphylococcus aureus osteomyelitis commonly involves persistent infection, inflammatory bone destruction, and impaired repair. Coordinating infection control with recovery of bone function remains an important therapeutic challenge. This review examines the relationships among pathogen persistence, innate immune responses, and bone repair, with inflammation resolution as its central focus. Particular attention is given to neutrophil clearance, macrophage efferocytosis, specialized pro-resolving lipid mediators, and metabolic adaptation. Biofilms, intracellular persistence, and canalicular colonization support persistent infection, while antimicrobial responses, immunoregulation, and tissue injury can coexist within a lesion. Resolution contributes to tissue homeostasis by limiting continued leukocyte recruitment, clearing dying cells, and adapting macrophage function, and overlaps spatially and temporally with infection control and repair. Vascular recovery, progenitor responses, and bone remodeling further determine the structural and mechanical properties of newly formed bone, whereas abnormal stromal responses and hypoperfusion may sustain infection and compromise repair. Most mechanistic evidence derives from S. aureus animal models and cell experiments. Selected efferocytosis and stromal pathways have received support in infection models, while the disease-specific roles of pro-resolving receptors and vascular–osteogenic mechanisms require further validation. Enhancing efferocytosis, modulating immune checkpoints, and targeting pathological stromal responses offer potential adjuncts to antimicrobial treatment, with the translational goal of restoring bone structure and function while maintaining infection control.