Magnesium alloys for orthopedic applications:A review on the mechanisms driving bone healing

Magnesium (Mg) alloys have attracted a wealth of attention in orthopedic fields for their superior mechanical properties, degradability, and excellent biocompatibility. Consistently, to resolve the issues on rapid degradation, more studies are dedicated to the researches on the composition design, preparation and processing, surface modification, the degradation modes of Mg alloys. Nevertheless, the mechanisms by which Mg alloys promote bone healing remain elusive. This review gives an account of specific mechanisms on Mg alloys promoting bone healing from four aspects, immunomodulatory, angiogenesis, osteogenesis and regulation of osteoclast function. We highlight the regulation of Mg alloys on the functional status and interactions of numerous cells that are involved in bone healing, including immune cells, osteogenic-related cells, osteoclasts, endothelial cells (ECs), nerve cells, etc., and summarize the signaling pathways involved, with the aim to provide the basis and support on future investigation on mechanisms on Mg alloys driving bone regeneration. More importantly, it provides a rationale and a general new basis for the application of Mg alloys in orthopedic fields.