Z-DNA: Critical Scaffold And Trigger In Peri-Implantitis Pathogenesis

This investigation aims to characterize the previously unexplored contribution of Z-DNA conformations to peri-implantitis biofilm architecture, virulence mechanisms, and host inflammatory responses, thereby identifying novel therapeutic targets for this challenging implant complication. Failed dental implants (n=12) were harvested from peri-implantitis patients (aged 35-65 years) following Ethics Committee approval. Biofilm architecture was analyzed using multi-species FISH probes with high-resolution CLSM to map three-dimensional microbial distribution patterns. Z-DNA's functional significance was assessed through selective conformation modulation using chloroquine (Z-DNA inhibitor) and CeCl₃ (Z-DNA stabilizer), followed by comprehensive analyses of biofilm integrity, viscoelastic properties, and bacterial communication dynamics. In vivo studies employed a validated rat peri-implantitis model with micro-CT volumetric analysis, histopathological assessment, and transcriptomic profiling of inflammatory pathways. We identified Z-DNA-dependent spatial organization in peri-implantitis biofilms with bacterial stratification correlating with biofilm maturation. Z-DNA reduction disrupted this architecture, decreased mechanical strength (53% reduction in Young's modulus, p<0.001), and inhibited biofilm formation. In vivo, Z-DNA enhancement accelerated peri-implant bone loss while upregulating nucleic acid-sensing pathways, particularly cGAS-STING and AIM2 inflammasome activation. This study establishes Z-DNA as a critical multifunctional component in peri-implantitis, serving both as structural scaffold and immunostimulatory trigger. Targeting Z-DNA represents a promising strategy for preserving implant longevity and function.