Potential role of titanium particles in peri-implantitis: Evidence from an integrated clinical, in vivo, and in vitro study.

Peri-implantitis represents a prevalent and significant biological challenge in oral implantology, and its etiology remains incompletely understood. The critical role of titanium particles in the progression of peri-implantitis has been largely overlooked, and a deeper understanding of their pathogenic mechanisms is essential for advancing biomaterial-based interventions. In this study, clinical samples were collected and cellular assays performed, along with the modified establishment of a titanium particle-induced animal model of peri-implantitis, to investigate the inflammatory mechanisms triggered by titanium particles. Results showed significantly elevated levels of titanium particles at diseased sites. Transcriptomic analysis revealed upregulation of inflammatory and osteoclast-related pathways and downregulation of osteogenic signaling. Further in vitro validation demonstrated that titanium particles under stimulatory conditions exacerbate inflammatory responses via hyperactivated autophagy. This study elucidates how titanium particles promote inflammation by modulating macrophage autophagy, highlighting their critical role in peri-implantitis and underscore the importance of targeting biomaterial-derived particles in future implant design and therapeutic strategies.