Role of molybdenum in material immunomodulation and periodontal wound healing: Targeting immunometabolism and mitochondrial function for macrophage modulation

Recently, strategies that can target the underlying mechanisms of phenotype change to modulate the macrophage immune response from the standpoint of biological science have attracted increasing attention in the field of biomaterials. In this study, we printed a molybdenum-containing bioactive glass ceramic (Mo-BGC) scaffold as an immunomodulatory material. In a clinically relevant critical-size periodontal defect model, the defect matched scaffold featured robust immunomodulatory activity, enabling long-term stable macrophage modulation and leading to enhanced regeneration of multiple periodontal tissues in canines. Further studies demonstrated that the regeneration-enhancing function of Mo-BGC scaffold was macrophage-dependent by using canines with host macrophage depletion. To investigate the role of Mo in material immunomodulation, in vitro investigations were performed and revealed that Mo-BGC powder extract, similar to MoO42--containing medium, induced M2 polarization by enhancing the mitochondrial function of macrophages and promoted a cell metabolic shift from glycolysis toward mitochondrial oxidative phosphorylation. Our findings demonstrate for the first time an immunomodulatory role of a Mo-containing material in the dynamic cascade of wound healing. By targeting the immunometabolism and mitochondrial function of macrophages, Mo-mediated immunomodulation provides new avenues for future material design in the field of tissue engineering and regenerative medicine.