Potential roles of bacterial extracellular vesicles in mesenchymal stem/stromal cell-mediated bone repair

The success of bone repair largely depends on mesenchymal stem/stromal cells (MSCs); however, under pathological conditions, dysregulation of the osteoimmune microenvironment often impairs MSC function and compromises bone regeneration.Bacterial extracellular vesicles (BEVs) are nanoscale membrane-bound structures released by bacteria that carry bioactive components such as proteins, lipids, and nucleic acids, mediating bacteria-host communication.Emerging evidence suggests that BEVs may participate in bone tissue homeostasis and repair by regulating immune responses, macrophage polarization, bone metabolism, and angiogenesis.Their effects vary with bacterial source: Vesicles derived from probiotic or commensal bacteria often show immunomodulatory and regenerative potential, whereas those derived from pathogenic bacteria may induce inflammatory responses and exacerbate bone resorption.These effects are also influenced by vesicle cargo, engineering status, and disease context.However, current evidence is predominantly preclinical, and no human clinical efficacy evidence for BEV-mediated bone repair was identified in the literature reviewed.Improvements in bone mass or reductions in bone resorption should not be equated with demonstrated fracture or bone-defect regeneration.In this review, we describe the effects of BEVs on MSCs and the osteoimmune microenvironment, summarize their potential mechanisms in bone repair, and discuss recent progress and future translational prospects of BEV-based strategies.