The increasing N2/N1 neutrophil ratio over time in human fracture hematoma indicates a transition from inflammation to regeneration

Our findings provide the first evidence of the coexistence and temporal evolution of N1 and N2 neutrophils within human fracture hematoma, consistent with their polarization characteristics observed in vitro. Moreover, these phenotypes exert distinct effects on osteogenesis, in alignment with the progressive increase of the N2/N1 ratio in vivo, supporting the gradual transition from inflammation to regeneration during the human fracture-healing cascade. Collectively, this study advances the understanding of neutrophil heterogeneity in bone regeneration and bridges fundamental immunobiological mechanisms with potential clinical translation.