A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

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AimTo explore a set of inflammatory biomarkers obtained from dentinal fluid (DF) from patients with symptomatic irreversible pulpitis (IP), reversible pulpitis (RP) and normal pulp (NP).MethodologyA cross‐sectional exploratory study was performed, recruiting 64 patients on the basis of their respective pulp condition. DF samples were obtained from all patients (23, from IP patients; 20, from RP patients; and 21, from NP patients). Quantification of biomarkers was performed using a Luminex® MAGPIX platform system and multiplex assay kits. The Kruskal–Wallis test was used for comparisons with regard to pulp state. A simple logistic regression model and the odds ratio (OR) with a 95% level of confidence (P = 0.05) were used to evaluate associations between biomarker levels and pulpal diagnosis. The performance discrimination of the biomarkers was evaluated through the construction of a receiver operating characteristic (ROC) curve by calculating the area under the curve (AUC) for IP versus RP after logistic regression modelling. Youden criteria were used to establish cut‐off points for biomarkers alone with AUC > 70 and P‐value < 0.05, or estimated probabilities from the multivariable logistic model.ResultsThe biomarkers that had significantly higher values in participants with IP versus RP were IL‐1α, VEGF‐α and FGF acid (P < 0.05). FGF acid (OR: 12.62; P = 0.0085; CI 95% 1.91–83.29) and VEGF‐α (OR: 2.61; P = 0.0252; CI 95% 1.13–6.03) were associated with pulp diagnoses of IP versus RP. The AUC‐ROC curve for FGF acid was 0.79. The model containing FGF acid, IL‐1α, IL‐6 and TIMP‐1 had an AUC‐ROC of 0.92 for IP versus RP with a significant difference from the FGF acid ROC curve (P = 0.0231).ConclusionsDentinal fluid could be used to assay pulpal mediators in the molecular diagnosis of pulpitis. Despite the limitation of the clinical diagnostics used in the present study, it was possible to detect a difference between irreversible symptomatic pulpitis and reversible pulpitis associated with the following combined biomarkers: FGF acid + IL‐6 + IL‐1α, +TIMP‐1.

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The aim of this report is to present the results of a personalised endodontic treatment for an immature molar, using regenerative endodontic procedure (REP) combined with non‐surgical root canal treatment (NSRCT), with 7 years of follow‐up. The tooth#3 presented combined endodontic pathologies in each root, with different pulpal and periapical status. A REP in the palatal (P) canal and a NSCRT in the mesio‐buccal (MB) and disto‐buccal (DB) canals were performed. Absence of clinical signs/symptoms and continuous palatal root development with apical closure were observed over 4‐years. After 5‐years an apical lesion in the MB root was observed. Both MB canals were selectively retreated by completely filling them with TotalFill BC RRM Fast Set putty. After 7‐years, the tooth remained functional and the apical lesion was resolving. The palatal root was completely mature. This case report reveals the potential for use of combined treatment approaches for immature multirooted teeth.