Biomarkers as a Diagnostic Tool for Assessing Traumatized Permanent Teeth in Pediatric Patients

Abstract

Background: Traumatic dental injuries (TDIs) present a significant public health challenge in pediatric populations, with prevalence ranging from 20% to 30%. Diagnostic uncertainty complicates the management of permanent teeth following trauma. Transient denervation frequently renders traditional thermal sensibility testing unreliable during the initial months post-injury, while external inflammatory root resorption can progress rapidly before radiographic detection. There is a critical need for non-invasive predictive tools to identify teeth at high risk for delayed complications. Objective: This prospective cohort pilot study aimed to determine if inflammatory cytokine and chemokine levels in the gingival crevicular fluid (GCF) of traumatized permanent teeth can serve as early biomarkers for adverse events, specifically pulp necrosis and external inflammatory root resorption. Methods: This study recruited a cohort of 27 pediatric patients presenting to Boston Children’s Hospital with TDIs in their permanent dentition, resulting in a total of 64 traumatized teeth for analysis. GCF was collected non-invasively for proteomic analysis using the Olink Target 48 cytokine assay to quantify key inflammatory mediators. Clinical variables and trauma types were recorded to assess correlations with adverse endodontic outcomes. Statistical analysis in R used Fisher’s Exact Tests and Firth’s Logistic Regression to assess associations between clinical parameters and adverse outcomes, supplemented by Kaplan-Meier survival curves for event-free probability. GCF proteomic data were analyzed via Benjamini-Hochberg adjusted t-tests to compare protein levels across injury and outcome categories, with longitudinal trends plotted for a subset of cases. Results: In this pediatric cohort (N=27), adverse events occurred in 17.2% of traumatized teeth (n=27). There was an average of 2.3 follow-ups per patient. While the majority of cases involved single trauma types, sustaining multiple simultaneous injuries significantly increased the risk of requiring treatment (OR = 4.65). GCF analysis revealed significantly elevated pro-inflammatory and resorptive biomarkers (adjusted p 0.05), including colony-stimulating factors, chemokines, and tissue degradation mediators. These molecular shifts correlated most strongly with crown fractures and minor displacements (). Exploratory analysis further identified a potential immunological transition based on complication type: isolated necrosis showed a trend toward acute pro-inflammatory signaling (IL-17C, IL-18, IL-15), whereas concurrent resorption was associated with elevated levels of the anti-inflammatory cytokine IL-27, suggesting a shift from an acute inflammation phase to a chronic phase. Conclusion: Gingival crevicular fluid analysis identified a distinct profile of changes in biomarkers associated with differences in trauma type and the development of adverse outcomes in traumatized teeth. While the restricted sample size and overlapping injury profiles limited our ability to isolate specific clinical triggers or a definitive timeline for these shifts, these findings underscore the potential for non-invasive GCF profiling to predict delayed endodontic complications and inform future diagnostic thresholds.