Regulation of bone immunity by metal ions: a review of mechanisms and application progress

The formation and repair of bone tissue depend not only on the activity of bone tissue cells but also on complex regulatory mechanisms mediated by the immune system. With the advancements of osteoimmunology in recent years, the functional roles of metal ions in this field have attracted extensive attention. Various metal ions, including zinc, magnesium, manganese, strontium, and copper, are demonstrated to influence the osteoimmune microenvironment and promote bone repair by modulating the biological functions of immune cells, especially the inflammatory response. However, the precise mechanisms through which metal ions orchestrate osteoimmunity have not been fully elucidated, and the underlying signaling pathways, as well as their internal interactions with cells involved in bone repair, require further in-depth investigation. This review summarizes the regulatory effects of various metal ions on macrophages, T cells, dendritic cells, and neutrophils, including phenotype polarization, maturation, differentiation, inflammatory cytokine expression, and underlying signaling pathways. Besides, this review further discusses the application of metal ion-doped biomaterials in bone tissue engineering, while also covers their functions in remodeling the osteoimmune microenvironment and highlights potential directions for future research directions.