Microbial Dysbiosis, Titanium Release, and Peri-implantitis.

The peri-implant mucosal barrier is a unique microenvironment where host-microbiome interactions take place on the surface of an implanted biomaterial. Therefore, peri-implant immunity not only is quintessential to oral health but also contributes to the maintenance of the biomaterial-tissue equilibrium in health. This review delves into the intricate interplay between host factors, biomaterial properties, and the microbiome with a focus on the mechanisms underlying peri-implant dysbiosis. Investigations into this complex milieu have led to the emerging understanding of titanium particles released from the implant as significant exposomes. When biomaterial breakdown occurs, implant degradation products form particles that are released in the peri-implant crevice, exerting profound effects on the local immune surveillance. Comparative analyses with natural dentition highlight the distinct immune responses elicited by titanium particles, thereby implicating them as a key modulator of peri-implant dysbiosis that differentiates peri-implant from periodontal inflammation. Nonetheless, disruptions in the homeostatic balance of host-biomaterial interactions are linked to pathogenic shifts of the peri-implant microbiome that are correlated with titanium particles in humans. Collectively, it is now well established that to elucidate the mechanisms governing peri-implant dysbiosis, this triangle of host-microbiome-biomaterial has to be conjointly investigated. This review highlights findings from studies that have underscored the multifaceted nature of peri-implant dysbiosis, emphasizing the intricate crosstalk between host immunity, biomaterial characteristics, and microbial ecology. These findings suggest that the titanium particle exposome may alter key inflammatory cascades in the peri-implant tissues including toll-like receptor activation and inflammasome and complement signaling, which lead to nonresolving destructive inflammation. The presence of abiotic danger signals in the form of implant degradation products in peri-implant tissues may make antimicrobial monotherapies largely ineffective for managing peri-implantitis. In turn, the future of peri-implantitis therapy seems to lie in the development of targeted host modulatory interventions against titanium-mediated inflammatory pathways.