A Protocol to Discover Endodontic Diagnostic Biomarkers After Traumatic Dental Injuries in Immature Teeth

Abstract

Introduction: Having an accurate diagnosis following a traumatic dental injury (TDI) is fundamental for appropriate, conservative treatment that will allow minimal destruction and maximum regain of function. However, following a TDI, the inflammation from the injury makes diagnosis unpredictable. The current recommendation is to delay treatment up to 8 weeks until a diagnosis can be determined, however a delay in treatment can lead to complications, such as the development of infection or the progression of external inflammatory root resorption (EIR). The gingival crevicular fluid (GCF) is readily accessible and has been shown contain biomarkers that can be used for diagnosis of the pulp status and of resorption. The aim of the study is to determine if biomarker levels measured in GCF are associated with infection or EIR of immature, permanent teeth after a TDI. Methods: Patients presenting to the Department of Dentistry at Boston Children’s Hospital with a TDI to an immature, permanent tooth will be followed over the course of 1 year to determine if the level of biomarkers present can predict the development of infection or EIR. The GCF will be collected using paper points at different intervals. Samples will be analyzed for 10 proinflammatory cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α) using a highly sensitive multiplex antibody-based array, Meso Scale Discovery (MSD). One biomarker of bone resorption, dentin sialoprotein (DSP), will be screened by using an ELISA panel. Results: IRB approval was obtained at HSDM and BCH, utilizing Smart IRB with HSDM as the primary site. The study was launched in March of 2024 and multiple patients have been recruited. Patient recruitment will continue over the next one year. After completion, we will compare biomarker expression in teeth of participants that developed disease versus matched controls that did not. The data will be statistically analyzed by assessing for normality, then a t-test or Wilcoxin-signed rank test will be used to test statistical differences in specific biomarkers that either predict the development of pathology or were present at a higher level at the time disease was identified. This method will be used to narrow the group of biomarkers that were consistently associated with disease. Conclusions: There will be a difference in the biomarkers of the GCF in a healthy tooth versus an immature, permanent tooth that has undergone a TDI and develops infection or EIR within the first year after the TDI.