Search Results (271)

Regenerative endodontics seeks to restore the vascularized pulp–dentin complex following conventional root canal therapy, yet reliable neovascularization within the constrained root canal remains a key challenge. This study investigates the development of an injectable, dual-curing hydrogel based on methacrylated decellularized amniotic membrane (dAM-MA) and compares its performance to a conventional gelatin methacryloyl (GelMA). The dAM-MA platform was designed for biphasic release, incorporating both free vascular endothelial growth factor (VEGF) for an initial burst and matrix-metalloproteinase-cleavable VEGF conjugates for sustained delivery. The dAM-MA hydrogel achieved shape-fidelity via thermal gelation at 37 °C and possessed tunable stiffness (0.5–7.8 kPa) after visible-light irradiation. While showing high cytocompatibility comparable to GelMA (>125% hDPSC viability), the dAM-MA platform markedly outperformed the control in promoting endothelial tube formation (up to 800 µm total length; 42 branch points at 96 h). The biphasic VEGF release from dAM-MA matched physiological injury kinetics, driving both early chemotaxis and late vessel maturation. These results demonstrate that dAM-MA hydrogels combine native extracellular matrix complexity with practical, dual-curing injectability and programmable VEGF kinetics, offering a promising scaffold for minimally invasive pulp–dentin regeneration. Full article

Background and Clinical Significance: Traumatic dental injuries, particularly complicated crown fractures of permanent incisors, are common in adolescents, with maxillary central incisors most frequently affected due to their prominent position. These injuries, often resulting from sports or accidents, require prompt management to prevent complications such as pulp necrosis or infection, which can compromise long-term prognosis. Fragment reattachment offers a conservative, esthetically favorable approach when the fractured segment is intact, with outcomes comparable to composite restorations. This case report underscores the importance of timely intervention and advanced restorative techniques in pediatric dentistry. Case Presentation: A 16-year-old male presented with a complicated crown fracture of the upper left central incisor sustained during a soccer game. The fracture extended subgingivally with pulp exposure. The patient preserved the fragment in saline. Treatment involved fragment reattachment using a dentin bonding agent and flowable composite resin, followed by single-visit root canal therapy due to delayed presentation (48 h). A glass fiber post was placed to reinforce the restoration due to significant coronal loss. Three years of follow-up visits (1, 3, 6, 12, 24, and 36 months) revealed no clinical or radiographic complications, with the tooth remaining asymptomatic and functional. Conclusions: This case underscores the effectiveness of fragment reattachment when combined with meticulous technique and long-term monitoring. Full article

Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article

Vital pulp therapy with calcium hydroxide or mineral trioxide aggregate (MTA) rapidly induces dystrophic calcification and promotes the accumulation of two members of small integrin-binding ligand N-linked glycoproteins: osteopontin (OPN) and dentin matrix protein-1 (DMP1). However, the precise relationship between these initial events and their roles in reparative dentinogenesis remain unclear. This study aimed to clarify the relationship between dystrophic calcification, OPN and DMP1 accumulation, and reparative dentin formation. Pulpotomy was performed on rat molars using MTA or zirconium oxide (ZrO₂). ZrO₂ was used as a control to assess pulp healing in the absence of dystrophic calcification. Pulpal responses were evaluated from 3 h to 7 days postoperatively via elemental mapping, micro-Raman spectroscopy, and histological staining. In the MTA-treated group, a calcium-rich dystrophic calcification zone containing calcite and hydroxyapatite was observed at 3 h after treatment; OPN and DMP1 accumulated under the dystrophic calcification zone by day 3; reparative dentin formed below the region of OPN and DMP1 accumulation by day 7. In contrast, these reactions did not occur in the ZrO₂-treated group. These results suggest that dystrophic calcification serves as a key trigger for OPN and DMP1 accumulation and plays a pivotal role in reparative dentinogenesis. Full article

This critical narrative review presents the concepts and methods that have been or are currently applied in the treatment of periapical tissue changes in mature and immature permanent teeth. Treatment success is defined as the healing of the inflammatory lesion in permanent teeth and, additionally, the completion of root development in immature teeth. Background/Objectives: Endodontics focuses on the prevention and treatment of diseases affecting the dental pulp and periapical tissues. Periapical changes have been managed using various methods depending on factors such as the extent of the lesion and the stage of root and apical development. Conventional root canal treatment, revitalization, and apexification have all been employed. Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for studies discussing different treatment approaches, materials, and the efficacy of techniques used over time in mature and immature permanent teeth. Results: This review includes seven case reports, seven case series, and three cohort studies, each detailing the treatment method, case characteristics, follow-up period, and treatment outcomes. Conclusions: Modern materials have significantly improved the outcomes of revitalization and apexification procedures. These methods can now compete with or even surpass the clinical effectiveness of conventional root canal therapy. Full article

MicroRNA (miR)-200c enhances osteogenesis, modulates inflammation, and participates in dentin development. This study was to investigate the beneficial potential of miR-200c in vital pulp therapy (VPT) by mitigating pulpitis and promoting dentin regeneration. We explored the miR-200c variations in inflamed pulp tissues from patients with symptomatic irreversible pulpitis and primary human dental pulp-derived cells (DPCs) challenged with P.g. lipopolysaccharide (Pg-LPS). We further assessed the functions of overexpression of miR-200c on odontogenic differentiation, pulpal inflammation, and dentin regeneration in vitro and in vivo. Our findings revealed a noteworthy downregulation of miR-200c expression in inflamed pulp tissues and primary human DPCs. Through the overexpression of miR-200c via transfecting plasmid DNA (pDNA), we observed a substantial downregulation of proinflammatory cytokines interleukin (IL)-6 and IL-8 in human DPCs. Furthermore, this overexpression significantly enhanced the transcript and protein levels of odontogenic differentiation markers, including Runt-related transcription factor (Runx)2, osteocalcin (OCN), dentin matrix protein (DMP)1, and dentin sialophosphoprotein (DSPP). In a rat model of pulpitis induced by Pg-LPS, we demonstrated notable benefits by local application of pDNA encoding miR-200c delivered by CaCO₃-based nanoparticles to reduce pulpal inflammation and promote dentin formation. These results underscore the significant impact of locally applied miR-200c in modulating pulpal inflammation and facilitating dentin repair, showcasing its ability to improve VPT outcomes. Full article

Aim: hydraulic calcium silicate-based cements (HCSCs) are widely used in endodontics for vital pulp therapy and other clinical procedures due to their favorable physicochemical and biological properties. This study evaluates the biological properties of two HCSCs—MTA Flow™ and MTA Flow™ White (in a 3:2 liquid-to-powder ratio, thick consistency)—on human dental pulp stem cells (hDPSCs). Methodology: hDPSCs were exposed to leachates from MTA Flow™, MTA Flow™ White, and ProRoot^® MTA. pH changes, cytotoxicity, cell proliferation, cell morphology, and cell death (apoptosis/necrosis) were assessed in vitro. Results: MTA Flow™ White and ProRoot^® MTA leachates produced a strongly alkaline pH (~10–12) compared to the negative control, whereas MTA Flow™ leachate caused a smaller pH increase (~9.4). Freshly mixed cements showed moderate cytotoxicity (around 40–60% cell viability at 100% concentration), while hardened cement leachates did not significantly affect cell viability. At 100% concentration, MTA Flow™ and MTA Flow™ White leachates significantly inhibited hDPSC proliferation and caused cell death, but at lower concentrations (≤50%) they supported cell viability and proliferation comparable to ProRoot^® MTA. hDPSCs exposed to MTA Flow™ and MTA Flow™ White leachates appeared more elongated morphologically than those exposed to ProRoot^® MTA. Notably, cells treated with MTA Flow™ White leachates were significantly smaller than those treated with MTA Flow™. Conclusions: MTA Flow™ and MTA Flow™ White, used in 3:2 thick consistency, demonstrated biocompatibility comparable to ProRoot^® MTA in vitro. While 100% leachates showed moderate cytotoxicity, lower concentration dilutions (≤50%) supported hDPSC viability, proliferation, and morphology. These findings support their potential as safe alternatives for vital pulp therapy. Further in vivo studies and dynamic models are needed to confirm long-term biological performance. Full article

Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Precision oncology seeks personalized therapies that selectively modulate tumor behavior, which is critical for improving patient outcomes. In this study, we evaluated the therapeutic potential of human dental pulp stem cell-derived extracellular vesicles (hDPSC-EVs) in three ATC cell lines (8505C, HTH83, KTC-2). Fluorescence and confocal microscopy confirmed the efficient, time-dependent internalization of hDPSC-EVs by ATC cells, with increased fluorescence intensity over 48 h. Functional assays revealed the selective inhibition of migration and invasion in a cell line-dependent manner, without affecting cell proliferation, viability, or tumorigenic traits, indicating a non-cytotoxic, context-specific modulation of tumor behavior. After 72 h of EV treatment, targeted qPCR of 92 cancer-related genes showed the strongest response in 8505C cells (24 genes; 16 up, 8 down), moderate changes in KTC-2 (16 genes; 14 up, 2 down), and few alterations in HTH83 (6 genes; 4 up, 2 down). Across all lines, FN1 emerged as a context-dependent target, downregulated in 8505C but upregulated in the other two. No broad pathway enrichment was observed, indicating the fine-tuning of key networks rather than wholesale reprogramming. Despite variations across cell lines, hDPSC-EVs consistently demonstrated no impact on cell proliferation and no evidence of cytotoxicity or tumorigenic behavior, with no adverse outcomes. These findings provide preclinical evidence for hDPSC-EVs as a promising, safe, and targeted therapeutic platform in precision oncology, particularly for aggressive cancers, like ATC, warranting further exploration in preclinical and clinical studies. Full article

Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article

Immunotherapy targeting the immune functions of the tumor microenvironment (TME) is beneficial for colorectal cancer; however, the response rate is poor. Ciprofloxacin is a fluoroquinolone-class antibiotic that is used to treat bacterial infections. The purpose of this study is to assess the mechanism of ciprofloxacin that enhances anti-PD1 in colorectal cancer. We found that ciprofloxacin induced cytosolic DNA, including single-stranded and double-stranded DNA, formation in mouse CT26 colorectal adenocarcinoma cells. Molecules in DNA-sensing signaling such as cGAS, STING, and IFNβ mRNA and protein expression were elicited after ciprofloxacin treatment in CT26 cells. STING siRNA abrogated the cGAS-STING pathway activation by ciprofloxacin. In vivo, ciprofloxacin exhibited a synergistic effect with anti-PD1 to suppress tumor growth in a CT26 syngeneic animal model without biological toxicity. The examination of TME revealed that ciprofloxacin, alone and in combination therapy, induced M1 and red pulp macrophage production in the spleen. In tumors, M1 and M2 macrophage levels were increased by ciprofloxacin, and CD8⁺ T cell granzyme B expression was increased after combination therapy. STING showed the highest expression in tumor specimens after combination treatment. Ciprofloxacin may enhance the anti-PD1 efficacy and modulate the TME through the cGAS-STING pathway. Full article

Euterpe oleracea Martius, also popularly known as açaí palm, is a palm tree of the Aracaceae family widely found in the Amazon region. Traditional plant use reports indicate the beneficial effects of açaí juice on fever, pain, and flu. Moreover, many studies have demonstrated the pharmacological potential of açaí, mainly the pulp and seed of the fruit, due to its chemical composition, which significantly consists of polyphenols. In recent years, there has been a growing interest in investigating the neuroprotective effects of açaí, with the potential for the prevention and treatment of neurodegenerative diseases, such as Alzheimer’s disease, mainly due to the increasing aging of the population that has contributed to the increase in the number of individuals affected by this disease that has no cure. Therefore, this review aims to evaluate the potential role of açaí fruit in preventing or treating cognitive deficits, highlighting its potential in Alzheimer’s disease therapy. Preclinical in vivo and in vitro pharmacological studies were utilized to investigate the learning and memory effects of the pulp and seed of the açaí fruit, focusing on antioxidant, anti-inflammatory, antiapoptotic, and autophagy restoration actions. Full article

Introduction: Successful root canal therapy relies on thorough cleaning and disinfection to eliminate microorganisms and residual pulp tissue. Advanced irrigation activation techniques, including Sonic, Ultrasonic, and Diode Laser activation, have improved cleaning efficacy, bacterial reduction, smear layer removal, and irrigant hydrodynamics. On the other hand, these irrigation activation techniques may lead to a temperature rise that may risk the surrounding periodontal tissue. Thus, this study aimed to investigate the temperature rise during different irrigation activation techniques at various time intervals and evaluate the efficacy of these techniques in removing biofilm-mimicking hydrogel BMH of a simulated root canal system in 3D-printed tooth models. Methods: Ten extracted human mandibular premolars, prepared to size 40/0.04 taper, and a hundred 3D-printed resin premolars with simulated main (0.25 mm) and lateral canals (0.15 mm at 3, 7, 11 mm from apex) were used; 50 of them were filled with biofilm-mimicking hydrogel (BMH). Five irrigation activation techniques were evaluated: Diode Laser, Ultrasonic, Sonic, XP-Finisher, and Control (n = 10). Temperature rises were measured on the extracted premolars after 30 and 60 s of activation using a thermographic camera in a controlled environment (23 ± 2 °C). Irrigant penetration, with and without BMH, was assessed in 3D-printed premolars using a 2.5% sodium hypochlorite-contrast medium mixture, visualized with a CMOS radiographic sensor. Penetration was scored (main canal: 3 points; lateral canals: 0–2 points) and analyzed with non-parametric tests. Results: Diode Laser activation technique resulted in the highest temperature rise on the external root surface, followed by the Ultrasonic, with no statistically significant difference observed among the remaining groups. In terms of efficacy, Ultrasonic and Sonic activation achieved significantly greater irrigant penetration in samples without BMH, and greater BMH removal in samples with BMH, compared to Diode Laser, XP-Finisher, and Control groups. Conclusions: In this in vitro study, Diode Laser caused the highest temperature rise, followed by Ultrasonic, with significant increases from 30 to 60 s. Temperature rise did not significantly affect penetration or BMH removal. Ultrasonic and Sonic irrigation techniques achieved the highest depth of penetration (without BMH) and biofilm-mimicking Hydrogel removal (with BMH) compared to Diode Laser, XP-Finisher, and Control. Full article

Background: The dentin–pulp complex plays a vital role in tooth health. Dentin forms the main body the tooth and continues to form throughout life to maintain homeostasis and provide protection against deleterious external stimuli. However, the detailed mechanism of dentin formation remains poorly understood, and there is a need for new regenerative therapies. This study therefore investigated whether primary dental pulp cells from mice could be used to establish a new culture system. Methods: Mouse mandibles were divided along the ramus to extract dental pulp tissue containing cervical loops. The extracted tissue was cultured in an incubator to promote cell out-growth and increase the number of cells available for experimentation. Results: Cultured cells formed mineralized nodules, confirmed by Alizarin red S staining. The expression levels of dentin sialo protein, bone gamma-carboxyglutamate protein, and type I collagen mRNAs in cultured dental pulp cells on day 15 were lower than those in intact mouse dental pulp tissue, and the expression of all mRNAs was confirmed through electrophoresis. Conclusions: This study established a primary culture system using dental pulp tissue extracted from mouse mandibular incisors. The results demonstrated that dental pulp cells can differentiate into odontoblast-like cells and form dentin-like mineralized nodules, thereby offering a useful system for studying dentin formation and odontoblast differentiation. Full article

Background: In recent years, thanks to the improvement of adhesive techniques, patients affected by tooth wear, related to erosion and/or parafunctional habits, can undergo restoration by adding only what has been lost of their dentition (additive approach). However, since not all clinicians are convinced that dental rehabilitation should be proposed in the early stages of exposed dentin, several treatments are often postponed. It is important to emphasize that, in the early stages, the clinical approach should remain conservative, focusing on dietary counseling, the modification of harmful habits, fluoride application, and risk factor management. Only when these preventive and non-invasive strategies prove insufficient, and the condition continues to progress, should invasive restorative treatments be considered. Unfortunately, epidemiological studies are reporting an increase in the number of young patients affected by erosive tooth wear, and not intercepting these cases earlier could lead to a severe degradation of the affected dentition. In addition, parafunctional habits are also becoming more frequent among patients. The combination of erosion and attrition can be very destructive, and may progress rapidly once dentin is exposed and the risk factors remain unaddressed. The aim of this report was to present a conservative full-mouth rehabilitation approach for severe erosive lesions and to provide a 10-year follow-up assessing the biological, functional, and esthetic outcomes. Methods: In this article, the postponed restorative treatment of a patient, suffering from severe tooth wear, is illustrated. The patient had sought dental treatment in the past; however, due to the already very compromised dentition, a conventional but very aggressive treatment was proposed and refused. Four years later, when the patient finally accepted an alternative conservative therapy, the tooth degradation was very severe, especially at the level of the maxillary anterior teeth. The combination of three different approaches, Speed-Up Therapy, BOPT (Biologically-Oriented Preparation Technique), and the 3 Step Technique, however, improved the capacity to successfully complete the difficult therapeutic task. Results: The biological goals (maintenance of the pulp vitality of all of the teeth and the minimal removal of healthy tooth structure) were accomplished, relying only on adhesive techniques. Conclusions: The overall treatment was very comfortable for the patient and less complicated for the clinician. At 10-year follow-up, biological, functional, and esthetic success was still confirmed. Full article

Pediatric dentistry continually seeks effective and efficient treatments for young patients, especially within pediatric endodontics, where cooperation can often be challenging. This in vivo study aimed to evaluate the effectiveness of a novel photodynamic therapy (PDT) protocol using a 5-aminolevulinic acid gel (Aladent, ALAD) combined with light irradiation during the endodontic treatment of primary teeth. This study included primary teeth requiring root canal therapy due to carious lesions or trauma, with clinical symptoms suggesting irreversible pulpitis or acute apical periodontitis. Following local anesthesia and isolation with a rubber dam, carious lesions were excavated, and access to the pulp chamber was established. Canal preparation included determining the working length and using a sequence of k-files. Afterward, ALAD gel was applied, and the patients were divided into two groups based on their visit duration (Group A with a single visit, Group B returning after one week). Microbiological analysis was conducted on the samples taken before and after treatment. The findings demonstrated significant antibacterial efficacy of the PDT protocol in reducing root canal bacterial load, suggesting ALAD-based PDT may serve as an alternative to traditional endodontic treatment in cases where retaining primary teeth is essential for orthodontic or strategic reasons. Clinically, improvement in symptoms and fistula resolution were observed. Treatment time, patient compliance, and protocol safety in pediatric applications are also discussed, highlighting the protocol’s potential to enhance clinical outcomes in pediatric endodontics. Full article