GaSe x Nanoparticles Modulate Neutrophil Function and Mitigate NET‐Driven Osteogenic Impairment in Osteomyelitis Therapy

ABSTRACT Osteomyelitis remains a major clinical challenge; however, current therapeutic strategies do not sufficiently address host immune defense, inflammatory microenvironment remodeling, or bone regeneration. Here, we show that excessive accumulation of neutrophil extracellular traps (NETs) in infected bone tissues contributes to osteomyelitis‐associated apoptosis and impaired osteogenesis. NETs disrupt PINK1/Parkin‐mediated mitochondrial quality control in osteoblast lineage cells, thereby promoting apoptosis, whereas inhibition of NET formation alleviates these pathological changes and improves bone repair in mice. Bone defects are aggravated in Prkn ‐knockout mice upon the induction of osteomyelitis, supporting the functional role of PINK1/Parkin‐dependent mitophagy in the repair of infected bone. As a therapeutic strategy, gallium–selenium nanoparticles (GaSe x ) exert potent antibacterial activity, redirect neutrophils from NET formation toward phagocytosis, preserve osteoblast mitochondrial homeostasis, attenuate excessive mitophagy, and ultimately promote the repair of infected bone defects in rats. Collectively, these findings support NET‐driven osteoblast mitochondrial injury as a critical repair‐limiting mechanism in osteomyelitis and establish GaSe x as a redox‐regulating platform that modulates this mechanism while preserving neutrophil antibacterial defense.