Traditional designs and developments of bone biomaterials mostly concentrate on the positive regulation of osteoblast lineage cells, but often ignore the importance of immune responses and the equilibrium between bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. Immune dysregulation is associated with an imbalance between pro-inflammatory and anti-inflammatory processes, which may influence the efficacy of bone therapy. Therefore, implanted biomaterials should appropriately and precisely modulate subsequent immune responses. Magnesium (Mg) has been used to fabricate various Mg alloys for bone repair because of its favorable attributes such as osteogenic potential, immune regulation characteristics, biodegradability, and biocompatibility. Various basic research and clinical trials have been already conducted in many countries to explore the physical properties of Mg-containing implants and their clinical outcomes in bone fracture and defect repair. Therefore, this review summarizes the immune response to Mg-containing implants, and further organizes the current research and development progress of Mg-containing implants. The review aims to offer an overview of the current knowledge on immunomodulation of Mg-containing implants and future challenges in their clinical application, which could provide further insight in the development of better strategies for the treatment of bone defect and fracture.

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.

Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.