Single-Cell Transcriptomics Reveal Microenvironment Alterations in Canine Peri-Implantitis.

Background: Peri-implantitis, a major contributor to dental implant failure, lacks comprehensive insights into tissue-specific heterogeneity as current researches predominantly focus on the whole peri-implant tissue rather than distinct molecular and cellular dynamics in gingiva and alveolar bone microenvironments. Furthermore, ethical challenges hinder the acquisition of healthy peri-implant tissues, limiting our understanding of peri-implantitis progression and the development of targeted therapies. Methods: We established a controlled peri-implantitis model in beagle dogs, enabling ethical collection of healthy control tissues. Single-cell RNA sequencing (scRNA-seq) transcriptomics profiling was conducted on gingiva and alveolar bone tissues from diseased and healthy controls. Additionally, flow cytometry was utilized to further verify the identified subclusters and their involvement in peri-implantitis. Results: Single-cell transcriptomic profiling unveiled a pronounced expansion of inflammation-associated cellular subsets in both gingival and alveolar bone microenvironments during peri-implantitis. Gingival tissues exhibited marked expansions in IL6+/IL18BP+ endothelial cell and CXCL8+ fibroblast, whereas APOD+ fibroblast dominated in peri-implantitis bone tissues. Gene-level profiling further identified upregulated pro-inflammatory chemokines (CXCL8, CXCL17, CCL24) within gingiva IL18BP+ endothelial cells. Notably, we discovered a unique ligand-receptor interaction C3 (APOD+ fibroblast)-C3AR1 (monocyte/macrophage) in alveolar bone tissue, implicating complement-dependent signaling in immune crosstalk. Conclusions: Our study provides the first comparative atlas of soft/hard tissue remodeling in peri-implantitis at single-cell resolution. The expansion of IL6+/IL18BP+ endothelial cell and CXCL8+ fibroblast in gingiva, alongside APOD+ fibroblast-driven C3-C3AR1 signaling in alveolar bone, highlights distinct microenvironmental reprogramming between soft and hard tissues. These findings not only identify potential therapeutic targets but also validate the translational relevance of the canine model for peri-implantitis research.