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, neutrophils and 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 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.

Keywords

Biodegradable molybdenum, Bone fracture, Bone repair, Macrophage, Neutrophil, Single-cell sequencing

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.