Spatial Transcriptomic Assessments of Gene Expression Profiles in Human Peri-Implant Lesions.

AIM: To analyse gene expression profiles in human tissue samples obtained from dental implant sites with or without peri-implantitis. MATERIALS AND METHODS: Soft-tissue biopsy samples obtained from patients presenting with implants with severe peri-implantitis and adjacent reference implants with no signs of peri-implantitis were analysed by spatial transcriptomics (n = 4), RNA-sequencing (n = 20) and immunohistochemistry (n = 38). RESULTS: The analysis disclosed evident associations between distinct gene clusters and specific tissue compartments in both groups of specimens. Samples from peri-implantitis sites showed higher levels of gene activity than samples from reference implant sites. Gene-set enrichment analysis revealed that several important biological pathways, for example, 'regulation of antimicrobial host response', 'collagen fibril organisation' and 'regulation of angiogenesis', were severely dysregulated in peri-implantitis lesions when compared to reference implant sites. Similarly, immunohistochemical evaluation showed elevated levels of proteins corresponding to the most up-regulated, differentially expressed genes (DEGs), which were identified by spatial transcriptomics and RNA-sequencing. CONCLUSIONS: Peri-implant lesions demonstrated associations between gene clusters and specific tissue compartments. Several biological pathways linked to the activation of host response towards bacterial insults were dysregulated in peri-implantitis specimens when compared to reference implant samples.