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Optimizing the surface properties of Ti-6Al-4V (Ti64) is a goal for enhancing osseointegration and mitigating adverse inflammatory responses in biomedical implants. This study investigated the osteogenic potential and immunomodulatory property of a titanium–tantalum–nitride (TiTaN) surface coating. Physicochemical characterization revealed that TiTaN demonstrated pronounced hydrophilicity (θ = 29.9° ± 3.7°). Biological performance was evaluated using human primary alveolar bone cell (hAVs) and RAW264.7 macrophage cell line. The hAVs displayed a good proliferation on TiTaN surfaces over 7 days, maintaining high cytocompatibility and supporting for osteogenic growth. Under pro-inflammatory (LPS+) conditions, TiTaN surfaces significantly attenuated nitric oxide production compared to the Ti64 control, indicating potent anti-inflammatory activity. In addition, the TiTaN surface consistently and significantly downregulated key pro-inflammatory mediators, including Il-6, Tnf-α, and Il-1β, across both early (day 1) and extended (day 7) culture periods. These findings demonstrate that tantalum incorporation creates a stable, sustained anti-inflammatory environment while preserving osteogenic compatibility. This superior immunomodulatory profile positions TiTaN as a highly promising candidate coating for improving the clinical success of orthopedic and dental implants.

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