Manganese Enhances the Osteogenic Effect of Silicon-Hydroxyapatite Nanowires by Targeting T Lymphocyte Polarization

Biomaterials encounter considerable challenges in extensive bone defect regeneration. The amelioration of outcomes may be attainable through the orchestrated modulation of both innate and adaptive immunity. Silicon-hydroxyapatite, for instance, which solely focuses on regulating innate immunity, is inadequate for long-term bone regeneration. Herein, extra manganese (Mn)-doping is utilized for enhancing the osteogenic ability by mediating adaptive immunity. Intriguingly, Mn-doping engenders heightened recruitment of CD4+ T cells to the bone defect site, concurrently manifesting escalated T helper (Th) 2 polarization and an abatement in Th1 cell polarization. This consequential immune milieu yields a collaborative elevation of interleukin 4, secreted by Th2 cells, coupled with attenuated interferon gamma, secreted by Th1 cells. This orchestrated interplay distinctly fosters the osteogenesis of bone marrow stromal cells and effectuates consequential regeneration of the mandibular bone defect. The modulatory mechanism of Th1/Th2 balance lies primarily in the indispensable role of manganese superoxide dismutase (MnSOD) and the phosphorylation of adenosine 5 '-monophosphate-activated protein kinase (AMPK). In conclusion, this study highlights the transformative potential of Mn-doping in amplifying the osteogenic efficacy of silicon-hydroxyapatite nanowires by regulating T cell-mediated adaptive immunity via the MnSOD/AMPK pathway, thereby creating an anti-inflammatory milieu favorable for bone regeneration. In the context of bone healing, the introduction of manganese-doped silicon-hydroxyapatite nanowires (Mn-SiHANWs) induces T helper (Th) 2 cells while concurrently inhibiting Th1 cell polarization. Mechanistically, the presence of Mn-SiHANWs activates manganese superoxide dismutase (MnSOD) and leads to the phosphorylation of adenosine 5 '-monophosphate-activated protein kinase (AMPK). This anti-inflammatory environment, characterized by elevated interleukin (IL)-4 and decreased interferon gamma (IFN-gamma), ultimately promotes bone marrow stromal cell (BMSC) osteogenesis.image