Fe-NC nanozymes-loaded TiO2 nanotube arrays endow titanium implants with excellent antioxidant capacity for inflammation inhibition and soft tissue integration

Titanium (Ti) and its alloys have been widely used as percutaneous and subcutaneous implants due to their excellent mechanical properties and biocompatibility. However, the aggregation of reactive oxygen species (ROS) and persistent inflammatory responses at the implant site severely affect the soft tissue integration of Ti implants, causing a series of biological complications. To address this issue, in this study, Fe-nitrogen-doped carbon single-atom nanozymes (Fe-NC nanozymes) loaded titanium oxide nanotube arrays (Fe-NC@TNT) were constructed by anodic oxidation and solvothermal method on medical titanium surfaces. The surface morphology, physical composition, enzyme-like catalytic activity, inflammatory response, and soft tissue compatibility of Fe-NC@TNT were investigated. The unique nanotube array fully exposes the catalytic active sites of Fe-NC nanozymes and significantly enhances their enzyme-like catalytic performance to eliminate superoxide anion, hydrogen peroxide, and more toxic hydroxyl radicals, which could effectively reduce the intracellular ROS levels of macrophages and fibroblasts, thereby inhibiting the inflammatory responses of macrophages and promoting the functional expression of fibroblasts. In vivo animal experiments have further demonstrated that Fe-NC@TNT can effectively regulate the immune response and promote the integration between the implant and the surrounding soft tissues.