Dopamine-mediated copper-loaded ZnTiO 3 antimicrobial coating with immunomodulatory properties effectively enhances vascularised osteogenesis on titanium implants

In this study, zinc (Zn) with osteogenic activity and copper (Cu) with angiogenic activity were simultaneously introduced into titanium dioxide nanotubes (TN) by means of anodic oxidation technique, hydrothermal reaction and dopamine (PDA) polymerisation effect (ZnTN-PDA-Cu). The ZnTN-PDA-Cu coating had favourable mechanical, hydrophilic, corrosion-resistant, and bioactive characteristics, according to the results. Zn2+ and Cu2+ could be continuously released from the coating and was pH-responsive. In addition, ZnTN-PDA-Cu showed good antibacterial properties against E. coli and S. aureus. Cellular assays revealed that RAW264.7 (immune), HUVEC (angiogenic) and MC3T3-E1 (osteogenic) exhibited good adhesion and proliferation activities on the ZnTN-PDACu coated Ti. The expression of anti-inflammatory markers, angiogenic markers and osteogenic markers was significantly up-regulated in ZnTN-PDA-Cu coatings at both the gene level and protein level. ZnTN-PDA-Cu also demonstrated the capacity to stimulate RAW264.7 towards M2 polarisation and HUVEC tube formation. In addition, it demonstrated the capacity to stimulate MC3T3-E1 towards osteogenic differentiation. In summary, the ZnTN-PDA-Cu coating had better antibacterial, anti-inflammatory, angiogenic and osteoinductive properties. The multifunctional coatings prepared in this study provide a promising new strategy and experimental basis for the design of antibacterial titanium surfaces with immunomodulatory functions.