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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).

PurposeThis study used cone-beam computed tomography (CBCT) to characterize mandibular molar root and canal morphology and its variability in Belgian and Chilean population samples.Materials and MethodsWe analyzed the CBCT images of 515 mandibular molars (257 from Belgium and 258 from Chile). Molars meeting the inclusion criteria were analyzed to determine (1) the number of roots; (2) the root canal configuration; (3) the presence of a curved canal in the cross-sectional image of the distal root in the mandibular first molar and (4) the presence of a C-shaped canal in the second mandibular molar. A descriptive analysis was performed. The association between national origin and the presence of a curved or C-shaped canal was evaluated using the chi-squared test.ResultsThe most common configurations in the mesial root of both molars were type V and type III. In the distal root, type I canal configuration was the most common. Curvature in the cross-sectional image was found in 25% of the distal canals of the mandibular first molars in the Belgian population, compared to 11% in the Chilean population. The prevalence of C-shaped canals was 10% or less in both populations.ConclusionIn cases of unclear or complex root and canal morphology in the mandibular molars, CBCT imaging might assist endodontic specialists in making an accurate diagnosis and in treatment planning.

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High donor variation makes comparison studies between different dental sources dubious. Dental tissues offer a rare opportunity for comparing the biological characteristics of haploidentical mesenchymal stem cells (MSCs) isolated from the same donor. The objective was to identify the optimal dental source of MSCs through a biological and functional comparison of haploidentical MSCs from gingival (GMSCs) and dental pulp stem cells (DPSCs) focusing mainly on their angiogenic potential. The comparison study included (1) surface markers expression, (2) mesodermal differentiation capacity (chondrogenic, adipogenic, and osteogenic), (3) proliferation, (4) migration potential, (5) ability to form colony units, and (6) angiogenic potential in vitro and in vivo. Comparative analysis showed no difference in the immunophenotypic profile nor for the trilineage differentiation potential. Proliferation of GMSCs was higher than DPSCs at day 6 (2.6-fold higher, P < 0.05). GMSCs showed superior migratory capacity compared to DPSCs at 4, 8, and 12 h (2.1-, 1.5-, and 1.2-fold higher, respectively, P < 0.05). Furthermore, GMSCs formed a higher number of colony units for both cell concentrations (1.7- and 1.4-fold higher for 150 and 250 starting cells, respectively, P < 0.05). GMSCs showed an improved angiogenic capacity compared to DPSCs (total tube lengths 1.17-fold higher and 1.5-fold total loops, P < 0.05). This was correlated with an enhanced release of vascular growth factor under hypoxic conditions. Finally, in the plug transplantation assay evaluating the angiogenesis in vivo, the DPSC and GMSC hemoglobin content was 3.9- and 4-fold higher, respectively, when compared to the control (Matrigel alone). GMSCs were superior to their haploidentical DPSCs in proliferation, migration, and angiogenic potentials. This study positions GMSCs in the forefront of dental cell sources for applications in regenerative medicine.

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.

The high percentage of bacteria adhering to the resorptive lacunae or in the flutes of files used in overinstrumented human teeth with infected root canals carry a potential risk for postoperative pain, clinical discomfort and flare-ups. The hazards observed in these circumstances do not support the one-visit treatment of teeth having acute or chronic periapical abscesses.