Nanocore-Shell Bone Filler Contained Mesoporous Silica Modified with Hydroxyapatite Precursors; Wrapped in a Natural Metal-Phenolic Network.

Various therapeutic strategies have been developed to address bone diseases caused by aging society and skeletal defects caused by trauma or accidental events. One such approach is using bone fillers, such as hydroxyapatite (HA) and bioactive glasses. Although they have provided effective osteogenesis, infection and inflammation due to the surgical procedure and uncontrolled ion release can hinder the efficiency of bone regeneration. In response to these challenges, immobilizing a neutral metal-phenolic network on the surface of osteoconductive nanoparticles would be the master key to achieving a gradual, controlled release during the mineralization period and reducing infection and inflammation through biological pathways. In this regard, a mesoporous silica nanocomposite modified by an HA precursor was synthesized to enhance bone regeneration. In addition, to improve the therapeutic effects, its surface was wrapped with a magnesium-phenolic network made from pomegranate extract, which can simultaneously produce anti-inflammatory and antibacterial effects. The obtained core-shell nanocomposite was characterized by its physicochemical properties, biocompatibility, and bioactivity. The in vitro studies revealed that the synthesized nanocomposite exhibits higher osteogenic activity than the control groups, as confirmed by alizarin red staining. Moreover, the nanocomposite maintained low toxicity as measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and increased antibacterial activity against Staphylococcus aureus and Escherichia coli compared with the control groups. Therefore, this research presents a promising strategy for bone regeneration, combining the advantages of mesoporous silica nanocomposite modified by an HA precursor with the beneficial effects of a magnesium-phenolic network.