Neuroimmune regulation of post-traumatic bone regeneration: focus on inflammatory switching and functional recovery

The regenerative repair after bone trauma is not merely an osteogenic process but a dynamic reconstruction involving the coordinated participation of multiple systems, including the nervous, immune, and vascular systems. In recent years, the regulatory role of the neuro-immune axis in bone regeneration has attracted increasing attention. Existing studies indicate that this axis may influence the quality of bone regeneration and functional recovery outcomes by modulating inflammation initiation, facilitating the transition from the inflammatory clearance phase to the reparative phase, and contributing to the remodeling of the local microenvironment. Specifically, neural signal-mediated regulation of early immune cell recruitment, macrophage polarization, and angiogenesis-osteogenesis coupling represents a critical upstream mechanism in post-traumatic bone regeneration. Conversely, an imbalance in the neuro-immune axis may be associated with adverse outcomes such as nonunion, chronic pain, and functional impairment. This article reviews the main mechanisms by which the post-traumatic neuro-immune axis regulates bone regeneration from four aspects: inflammation initiation, inflammation switching, microenvironment remodeling, and functional repair, and summarizes the research progress of related intervention strategies. Overall, targeting the neuro-immune axis may provide novel therapeutic strategies for promoting bone healing and improving functional recovery; however, most current evidence is derived from animal experiments, mechanistic studies, or early translational explorations, and its clinical value remains to be further validated.