Abstract
BACKGROUND: Solubilized endogenous dentine extracellular matrix components (dECMs) are potent mediators in pulp regeneration and could potentially promote similar healing effects in diseased periradicular tissues by upregulating local mesenchymal stem cell-derived regenerative events. AIMS: (1) Determine if endodontic treatment outcomes with irrigation regimes promoting dECM release (17% ethylenediaminetetraacetic acid [EDTA]) are equivalent to conventional regimes (5.25% sodium hypochlorite [NaOCl]) in mature permanent teeth with asymptomatic apical periodontitis. (2) Explore changes in pain scores, expressions of periradicular tissue fluid (PTF)-derived inflammatory mediators, and volumtric changes in lesion size between the different irrigant regimes. METHODS: Forty single-rooted teeth, from 37 healthy adults, were block randomized into parallel groups of irrigation with either 17% EDTA, optimized for dECM solubilization, or 5.25% NaOCl (n = 20). All other aspects of the endodontic protocol were standardized over two visits with 14 days of calcium hydroxide intracanal medicament. Patient-reported pain scores were recorded at six hours and then daily for one week post-instrumentation and post-obturation. PTF samples were collected pre-instrumentation and pre-obturation, where analyte profiles (pg/TPC) were determined using an O-link Target-48 cytokine array. Treatment outcomes were clinically and radiographically assessed with cone beam computed tomography at 1 year using dichotomous criteria (favourable/unfavourable) based on volumetric change in lesion size. Participants, operators and assessors were blinded, and per-protocol analyses were conducted using binary logistic regression models with initial alpha values for statistical comparisons set at p < .05. RESULTS: A 90% recall rate was achieved at one year (NaOCl: 19; EDTA: 17). Favourable outcomes were observed in 89.5% of treatments using NaOCl and 94.1% of treatments using EDTA irrigation, with median lesion volume reductions of 92.5% (IQR: 67.33-99.13) and 95.84% (IQR: 78.81-100), respectively, (p > .05). Odds of unfavourable periradicular healing with EDTA irrigation were 0.53 [95% CI: 0.04-6.44; p > .05]. No serious adverse effects or atypical pain patterns were reported, although two acute exacerbations occurred post-instrumentation with NaOCl irrigation (p > .05). Target-48 panels consistently detected 15 inflammatory analytes in both groups (CCL-2, -3, -4; CSF-1; CXCL-8; HGF; IL-1β, -6, -18; MMP-1, -12; OLR-1; OSM; TNFSF-10; VEGF-A), all of which reduced pre-obturation. At this stage, IL-6 and -18 were significantly more abundant in the intervention group (p < .05). CONCLUSIONS: Therapeutic irrigant regimes promoting dECM solubilization resulted in one-year treatment outcomes equivalent to conventional irrigant protocols with no serious adverse effects reported.