IgG‐Complement Adsorption Behavior Activates Macrophage Mediated Early Immune Responses on Zirconia Implants

Zirconium implants have gained popularity among clinicians due to their superior mechanical properties. However, zirconium implants usually perform less well in early osseointegration than titanium implants. And the degree of severity of the acute inflammation resulting from macrophage activation after implantation determines the result of the implantation. The mechanism by which zirconia implants cause more acute inflammation compared to titanium implants is currently unknown. Here, the complement activation on zirconium oxide is demonstrated, which causes differences in inflammation compared to titanium oxide. More adsorption of immunoglobulin G (IgG) and complement protein C1q together with the more efficient triggering of the complement system is shown to occur on ZrO2 surfaces. Molecular dynamics (MD) simulations further reveal that IgG exhibits more accessible binding sites on ZrO2 surfaces due to its hydrophobicity, leading to more efficient complement activation. Reduced inflammation of hydrophilized ZrO2 compared to non-treated ZrO2 demonstrates the role of hydrophobicity in the higher inflammation of ZrO2. The results reveal that complement activation due to conformational changes and greater adsorption of IgG and C1q on ZrO2 triggers inflammation caused by macrophages, providing new insights for implant design and performance optimization.