Minghao Zhou, Miaomiao Tian, Jingwei Yu, Jiaxin Kang, Miaomiao Chen, Yue Yuan, Lizhi Liu, Hongbo Wei
Peri-implant diseases (PID) remain major threats to titanium implant longevity, largely due to insufficient soft tissue integration (STI), which weakens the biological seal and promotes a pathogenic-immunological amplification loop involving early Staphylococcus aureus colonization and oxidative stress-induced macrophage dysfunction. Here, we developed a dual-targeting biomimetic nanozyme platform by camouflaging molybdenum diselenide (MoSe2) nanoflowers with membranes derived from S. aureus-pre-stimulated macrophages (SPMM). This biomimetic design couples S. aureus-targeting of SPMM with the photothermal activity of MoSe2 to achieve targeted contact-enhanced bacterial eradication, while integrating macrophage-targeting of SPMM with reactive oxygen species (ROS)-scavenging activity of MoSe2 to alleviate oxidative stress in macrophages. By disrupting the pathogenic-immunological amplification loop, MoSe2@SPMM reshaped a pro-regenerative peri-implant immune microenvironment. In a rat implantation model, near-infrared (NIR)-triggered MoSe2@SPMM suppressed bacterial colonization, promoted macrophage reprogramming, and preserved endothelial and fibroblast functions, thereby enhancing angiogenesis, matrix remodeling, connective tissue attachment, and integrin-mediated tissue-implant adhesion. This biomimetic nanozyme strategy provides a rational framework for coordinating pathogen control and immune regulation to promote peri-implant STI.