Inflammatory responses to micro/nano-structured titanium surfaces with silver nanoparticles in vitro

The inflammatory response to implants is a key stage of promoting angiogenesis, wound healing and regulating osteogenesis. Macrophages play an important role in inflammation due to their high plasticity. However, few reports have focused on the effect of antibacterial materials on macrophage polarization. In this work, micro/nano-structured titanium (MNT) was obtained through micro-arc oxidization. We synthesized silver nanoparticles (AgNPs) with an average diameter of 20 nm and immobilized AgNPs onto MNT via polydopamine to generate AgNP-decorated MNT (AgPD-MNT). Further, we investigated the antibacterial activity of the materials and the macrophage behaviors on the materials. The X-ray photoelectron spectroscopy analysis indicated that metallic Ag and dopamine/polydopamine existed on the AgPD-MNT surface. The concentration of released Ag was less than 8 ppb after 21 days. AgPD-MNT showed high antibacterial efficacy against Escherichia coli without cytotoxicity toward osteoblasts. The macrophage proliferation and morphology results showed that AgPD-MNT had no cytotoxicity within 5 days and caused apoptosis after 7 days. The flow cytometry, enzyme-linked immuno sorbent assay and quantitative real-time polymerase chain reaction results manifested that the material groups (PD-MNT, MNT and AgPD-MNT) stimulated switching of macrophages to mixed phenotypes (M1-M2) in the early stage (within 5 days), whereas the expression of M2 macrophages was upregulated in the later stage. Among the material groups, AgPD-MNT showed the most significant regulation of macrophage polarization. Especially, AgPD-MNT induced adherent-macrophage apoptosis and upregulation of I kappa B to reduce inflammation. Hence, AgPD-MNT could promote wound healing and reduce the risk of implant-associated infection.