Biodegradable molybdenum intramedullary nails facilitate fracture repair through neutrophil-mediated immune response

Molybdenum (Mo) has been considered as a promising biodegradable metal for fracture fixation owing to its favorable mechanical properties and controlled degradation behavior. Although existing studies have confirmed the osteoinductive potential of molybdenum-based materials, the biological mechanism through which molybdenum facilitates bone healing remains poorly elucidated. This study systematically evaluated the fracture repair performance of biodegradable Mo intramedullary nails in a rat femoral fracture model and further characterized the early peri-implant immune microenvironment using single-cell RNA sequencing in a day-3 femoral implantation model. Compared to the titanium (Ti)-based implant, the Mo-based implant significantly accelerated fracture healing, as evidenced by improved radiographic and micro-CT outcomes, enhanced matrix deposition, and mineralized bone formation, and increased expression of osteogenesis-related markers. Single-cell transcriptomic analysis revealed that the Mo-based metal induced a distinct immune landscape characterized by enrichment of neutrophils and macrophages and enhanced crosstalk between these two myeloid populations. Among the identified subsets, Cd177 ⁺ neutrophils and Spp1 ⁺ macrophages emerged as key potential cell populations associated with the pro-regenerative effect of Mo metal. Further ligand-receptor analysis, molecular docking, and histological validation suggested that these two subsets may interact through the Fn1-Syndecan-1 axis. Collectively, our findings indicate that the biodegradable Mo implant can promote fracture healing by remodeling the early osteoimmune microenvironment, and reveal a candidate neutrophil-macrophage intercellular communication mechanism identified in the implantation model that may underlie Mo-induced bone repair.