Enhancing the immunomodulatory osteogenic properties of Ti-Mg alloy by Mg²⁺-containing nanostructures

Facilitating an appropriate immune response is crucial for promoting bone tissue regeneration upon biomaterial implantation. In this study, the Mg²⁺-containing nanostructures on the surface of Ti-1.25Mg alloy were prepared by a one-step hydrothermal reaction method via regulating pH value to enhance the immunomodulatory osteogenic properties of Ti-Mg alloys. In neutral (HT7) or alkaline (HT9) hydrothermal treatment (HT) solution, the size of MgTiO₃ nanostructures formed on the surface of Ti-1.25Mg alloy is smaller than that in acidic HT solution (HT5), and lamellar Mg(OH)₂ nanostructures are found in HT7 and HT9. In addition, the sample surface has a lower roughness and higher wettability with increasing pH value. The Mg²⁺-containing nanostructures on the Ti-1.25Mg alloy inhibited inflammatory response by promoting the polarization of M2 macrophages, thereby promoting osteogenesis in vitro. The micro-CT and histological assessment proved that the regeneration of bone defect was faster in HT7 than the Ti-1.25Mg in vivo. Mechanically, Mg²⁺-containing nanostructures can mediate the immune response of macrophages via upregulating integrins α5β1 and inhibiting Toll-like receptors (TLR-4), subsequently inhibiting the NF-κB signaling pathway. Overall, osteoimmunity-regulating Mg²⁺-containing nanostructures on Ti-1.25Mg present a promising biomaterial for bone repair.