Resveratrol-loaded TiO₂ Nanotube Array Inhibits Inflammatory Response And Promotes Bone Repair And Its Mechanism

Titanium and its alloys are widely used in bone implant materials due to their good mechanical properties,biocompatibility and corrosion resistance.However,the titanium surface is biologically inert,and in the early stage of implantation,the inflammatory reaction occurring around the implant hinders bone repair and osseointegration,and thus implantation failure often occurs.It has become a research hotspot and focus of titanium alloy bone implant materials by nanometering the surface of titanium alloy and loading anti-inflammatory drugs to develop new functional coatings.In this study,a uniform size titanium dioxide nanotube array was prepared on the surface of titanium by electrochemical anodization,and resveratrol was loaded onto the surface of the nanotube array to achieve in-situ release of the drug.Macrophages stimulated by lipopolysaccharide as an early inflammation model,bone marrow mesenchymal stem cells of 12-month-old mice as osteogenic differentiation model cells,which reduce the release of reactive oxygen species,inhibit early inflammation and promote osteogenic differentiation.Biological effects are studied.The results show that after the electrochemical anodization of industrial pure titanium,the titanium dioxide nanotubes are evenly arranged on the surface of the material;then the resveratrol is coated on the surface of the nanotube by physical adsorption to prepare the titanium dioxide nanoparticle loaded with resveratrol.Tube array surface.When the surface covered resveratrol had a mass of 15?g/cm~2,the surface was non-toxic to macrophages and BMSCs.Compared with the pure titanium control group,the surface significantly inhibited the inflammatory response of lipopolysaccharide-induced macrophages,and the inhibitory effect was dose-dependent with the amount of resveratrol supported.When the resveratrol loading was 15?g/cm~2,the concentration of active oxygen decreased by about 50%,the inhibition rate of NO reached 75%,and the protein expression of inflammation-related factors TNF-?and IL-1?decreased by about 88%and 82%,at the molecular level,the mRNA expression levels of TNF-?and IL-1?and iNOS were also significantly lower than those of the pure titanium group.At the same time,the surface can also reduce the expression of reactive oxygen species in osteoblasts,the inhibition rate reaches 36%,the surface can also significantly promote the expression of alkaline phosphatase and calcium nodules in osteoblasts,and improve the osteogenic differentiation related factor ALP.Upregulation of OCN,OPN,COL-1 and Runx2,and concentration-dependently of TNT-Res reduced the phosphorylation level of NF-?B in macrophages and osteoblasts.The above results indicate that titanium materials after anodization and resveratrol loading can significantly inhibit early inflammatory reaction and promote osteogenic differentiation by inhibiting the activation of NF-?B signaling pathway,and TNT-Res(Resveratrol-Titanium dioxide nanotubes)may It is an effective implant for improving osseointegration ability.