AbstractAimTo profile, for the first time, the gingival crevicular fluid (GCF) of intrabony defects against a wide array of inflammatory and regenerative markers.Materials and methodsTwenty‐one patients contributed one intrabony defect and one periodontally healthy site. Clinical and radiographic measures were obtained. GCF samples were analyzed with multiplex bead immunoassays over 27 markers previously identified by our group. Comparisons were performed using Wilcoxon matched‐pairs signed‐ranks tests, using a Bonferroni corrected α = 0.05/27 = 0.0019.ResultsIntrabony defect sites presented significantly increased GCF volume and disease‐associated clinical and radiographic characteristics (p < .05). Intrabony defect sites presented significantly increased IL‐1α, IL‐1β, IL‐6, IFN‐γ, and MMP‐8 levels compared with periodontally healthy sites (p < .0019). For regeneration markers, significantly higher FGF basic and VEGF levels were observed (p < .0019). Notably, traits of cell senescence were identified for the first time in the GCF.ConclusionsThe differentiation of intrabony defects from periodontally healthy control sites can be based on clinical and radiographic measures and on a differentiated GCF profile that is site‐specific. Alongside catabolic processes, through significant up‐regulation of inflammation and connective tissue remodeling, unique molecular characteristics of intrabony defects may render them a microenvironment amenable to regeneration. Traits of the senescence‐associated secretory phenotype may suggest the existence of senescent cells during periodontal inflammation in intrabony defects.