Resveratrol-loaded titania nanotube coatings promote osteogenesis and inhibit inflammation through reducing the reactive oxygen species production via regulation of NF-κB signaling pathway

Highlights: • Resveratrol-loaded titania nanotube (TNT-Res) coatings are fabricated on the titanium surfaces for bone repair. • TNT-Res coating decreases the ROS production in macrophage cell lineage RAW 264.7 and bone mesenchymal stem cells (BMSCs). • TNT-Res coating inhibits the inflammation of RAW264.7 cells and increases the osteogenic differentiation of BMSCs. • ROS-mediated regulation of NF-κB signaling pathway is involved in the above phenomenon. Although titanium and its alloys are widely used in bone surgeries, the implantation failures caused by sterile inflammation still occur. The excessive reactive oxygen species (ROS) in the peri-implant region are considered to cause inflammation and impede the osseointegration of titanium implants. In this study, a coating of resveratrol-loaded titania nanotube (TNT-Res) for eliminating ROS was fabricated on titanium surface through electrochemical anodization and following surface adsorption of resveratrol. The resveratrol concentration of released from TNT-Res coating was controlled by modulating the loading amount. The ROS production in macrophage cell lineage RAW 264.7 and bone mesenchymal stem cells (BMSCs) were significantly decreased when cultured on TNT-Res coatings. The pro-inflammatory factors, including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), and NO produced by RAW 264.7 cells were reduced when cells were cultured on TNT-Res coatings. These results proved that the TNT-Res coating can effectively eliminate ROS and inhibit inflammation. Moreover, the osteogenic indicators, including alkaline phosphatase (ALP) production, extracellular calcium deposition, and osteogenesis-related gene expression, including collagen (Col-), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2), were significantly promoted for TNT-Res groups, which demonstrated that the TNT-Res coating can enhance the osteogenic differentiation of BMSCs. Additionally, the phosphorylation of nuclear factor κ-B (NF-κB) were down-regulated both in RAW 264.7 cells and BMSCs, which indicated that the TNT-Res coating could inhibit inflammation and promote osteogenesis by inhibiting the activation of NF-κB signaling pathway. The TNT-Res coating could be an effective implant surface for improving osseointegration ability of titanium implants.