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27 pages, 4347 KB  
Review
Collagen Scaffolds in Regenerative Endodontic Procedures: Current Evidence, Limitations, and Future Perspectives
by Qiong-Ling Shi, Xiao Zhu, Chen Chen, Jing-Yi Chen, Dan-Yang Lu, Ying Shi, Yan-Qi Chen and Zhi-Fang Wu
Polymers 2026, 18(7), 894; https://doi.org/10.3390/polym18070894 - 7 Apr 2026
Abstract
Predictable pulp-dentin regeneration continues to represent a major challenge in regenerative endodontic procedures (REPs). Although collagen-based scaffolds are widely investigated for their excellent biocompatibility, their ability to deliver consistent clinical and histological outcomes requires critical evaluation. This review summarizes recent advances in the [...] Read more.
Predictable pulp-dentin regeneration continues to represent a major challenge in regenerative endodontic procedures (REPs). Although collagen-based scaffolds are widely investigated for their excellent biocompatibility, their ability to deliver consistent clinical and histological outcomes requires critical evaluation. This review summarizes recent advances in the application of collagen scaffolds for REPs. Clinical studies demonstrate that these scaffolds support high tooth survival rates and promote vitality recovery, root wall thickening, and apical closure. However, consistent root lengthening remains elusive. Histologically, the newly formed mineralized tissue from collagen scaffolds within REPs tends to be cementum-like or bone-like rather than reparative dentin, a pattern closely associated with the physicochemical properties of collagen, including pore size, porosity, concentration, stiffness, viscosity, and viscoelasticity. We conclude that while collagen scaffolds represent a “promising platform” for REPs due to their biocompatibility and clinical performance, current evidence indicates that they do not consistently achieve true pulp-dentin regeneration. We therefore propose targeted modification and advanced tissue engineering strategies to direct genuine regeneration. This review offers a framework for the rational design of next-generation collagen constructs toward more predictable regenerative outcomes. Full article
(This article belongs to the Section Polymer Applications)
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16 pages, 4956 KB  
Article
Orthodontically Induced External Root Resorption: A Finite Element Analysis
by Radu-Andrei Moga, Cristian Doru Olteanu and Ada Gabriela Delean
J. Clin. Med. 2026, 15(7), 2503; https://doi.org/10.3390/jcm15072503 - 25 Mar 2026
Viewed by 293
Abstract
Background/Objectives: This finite element analysis (FEA) assessed stress distribution in the tooth and dentin within an intact periodontium under 4 N of force and five orthodontic movements (intrusion, extrusion, rotation, tipping, and translation), using four failure criteria commonly used in numerical dental [...] Read more.
Background/Objectives: This finite element analysis (FEA) assessed stress distribution in the tooth and dentin within an intact periodontium under 4 N of force and five orthodontic movements (intrusion, extrusion, rotation, tipping, and translation), using four failure criteria commonly used in numerical dental studies. Secondly, differences between brittle- and ductile-like failure criteria were found, and the most accurate criterion was determined. Additionally, movements more prone to inducing external orthodontic root resorption were assessed. Methods: Using nine 3D models of the second lower premolar, 180 numerical simulations were performed. The models were anatomically accurate based on CBCT scans. FEA employed the brittle-like Maximum Principal (MaxP), Minimum Principal (MinP), and ductile-like Von Mises (VM) and Tresca (T). Results: The results showed that tipping was less prone to external orthodontic root resorption than translation, extrusion, intrusion, and rotation, which showed areas of high stress concentration in the cervical third of the root. High-stress areas were visible only when the dentin-pulp-NVB components were separately analyzed, and not when the entire tooth structure was assessed. Only by correlating the qualitative with the quantitative results could the difference between brittle-like and ductile-like failure criteria be seen. Conclusions: In total, 4 N of applied orthodontic force can induce limited islands of external orthodontic root resorption (intrusion–extrusion on the vestibular side, rotation–translation on the lingual and distal–lingual sides). The ductile-like failure criteria maintained the accuracy of the results across all FEA simulations, while the brittle-like criteria showed various quantitative and qualitative inconsistencies. Full article
(This article belongs to the Special Issue Oral Hygiene: Updates and Clinical Progress: 2nd Edition)
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14 pages, 1242 KB  
Article
Clinical and Biological Evaluation of Chemo-Mechanical Caries Excavation with Brix 3000 in Primary Molars: An 18-Month Prospective Study
by Zornitsa Lazarova and Nadezhda Mitova
Medicina 2026, 62(4), 615; https://doi.org/10.3390/medicina62040615 - 24 Mar 2026
Viewed by 165
Abstract
Background and Objectives: Caries in primary teeth are characterized by rapid and often asymptomatic progression, with early dentin involvement and potential extension to the pulp. Untreated lesions may lead to complications that affect the development of the permanent dentition. The aim of [...] Read more.
Background and Objectives: Caries in primary teeth are characterized by rapid and often asymptomatic progression, with early dentin involvement and potential extension to the pulp. Untreated lesions may lead to complications that affect the development of the permanent dentition. The aim of this prospective study was to evaluate the clinical and biological effectiveness of chemo-mechanical controlled caries excavation using Brix 3000 compared to conventional treatment in primary molars over an 18-month follow-up period. Materials and Methods: A total of 82 children aged 4–7 years were included, each presenting with at least one carious lesion in a primary molar classified as International Caries Detection and Assessment System (ICDAS II) code 05 or 06. The carious lesions were divided into two groups according to the method of excavation: Group 1 (control), which contained 40 lesions treated with conventional bur excavation, and Group 2, which contained 42 lesions treated with chemo-mechanical excavation using Brix 3000. In all cases, excavation was controlled using a fluorescence-based device (ProFace). Clinical performance was evaluated using an assessment protocol adapted from the FDI (Fédération Dentaire Internationale) clinical criteria for the evaluation of direct and indirect restorations, with particular emphasis on biological outcomes. Follow-up examinations were performed after 1 week and 1, 3, 6, 12, and 18 months, and included radiographic evaluations. Results: After 18 months, chemo-mechanical caries excavation with Brix 3000 demonstrated a biological success rate of 100%, with no reported acute symptoms or complications. Esthetic criteria showed a success rate of 65% at 18 months, while anatomical and functional criteria demonstrated success rates of 95% and 98%, respectively. In the conventional bur excavation group, biological success reached 100%, while the esthetic, anatomical, and functional success rates were 61.3%, 93.5%, and 100%, respectively. No significant differences were observed between groups (p > 0.05). Conclusions: Chemo-mechanical controlled caries excavation using Brix 3000 represents a clinically effective and biologically reliable alternative to conventional caries excavation for the treatment of carious lesions in primary molars. Full article
(This article belongs to the Section Dentistry and Oral Health)
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20 pages, 6375 KB  
Article
Extracellular Vesicles Derived from Human CD24+ Dental Papilla Stem Cells Promote Vascularized Dental Pulp Regeneration
by Jie Li, Tian Chen, Cheng Liang, Peini Lin, Weidong Tian, Zhi Liu and Lei Liu
Biomolecules 2026, 16(3), 390; https://doi.org/10.3390/biom16030390 - 5 Mar 2026
Viewed by 449
Abstract
Pulp necrosis remains a significant clinical challenge in dentistry, as current therapeutic approaches fail to achieve functional pulp regeneration. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, offer new opportunities for regenerative strategies. In this study, we focus on CD24+ human [...] Read more.
Pulp necrosis remains a significant clinical challenge in dentistry, as current therapeutic approaches fail to achieve functional pulp regeneration. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, offer new opportunities for regenerative strategies. In this study, we focus on CD24+ human dental papilla cells (CD24+ hDPCs), a functionally defined subpopulation previously characterized as having superior regenerative potential, and evaluate the regenerative potential of their derived EVs (CD24+ EVs) in pulp-like tissue regeneration. CD24+ EVs significantly enhanced the proliferation, migration, and osteo/odontogenic differentiation of human dental pulp stem cells (hDPSCs) and markedly promoted endothelial tube formation in vitro. In a treated dentin matrix (TDM)-based ectopic regeneration model, CD24+ EVs increased cellular accumulation within the regenerated tissue and robust angiogenesis, inducing the formation of well-organized, highly vascularized pulp-like tissue with dense cellular architecture and positive DSPP expression. Together, these findings suggest that CD24+ EVs concurrently enhance cell migration, odontogenic differentiation, and angiogenesis, and support a promising cell-assisted EV strategy grounded in functionally defined cellular subpopulations for pulp-like tissue regeneration. Full article
(This article belongs to the Section Molecular Medicine)
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11 pages, 1463 KB  
Article
Effect of Autologous Bioactive Concentrated Growth Factor and Residual Dental Pulp on Dentin–Pulp Complex Regeneration
by Abeer Ezat Wahba, Safwat Elwaseef, Huda Ibrahim Mostafa, Weal B. Abdelhameed, Ahmed Mostafa Abbas and Ashraf Mohamad Emran
Biomedicines 2026, 14(3), 537; https://doi.org/10.3390/biomedicines14030537 - 27 Feb 2026
Viewed by 357
Abstract
Background/Objectives: This study aimed to evaluate the regenerative potential of autologous concentrated growth factor (CGF) combined with residual pulp tissue in immature dog teeth using a histological and histomorphometric analysis. Materials and Methods: Thirty immature anterior and premolar teeth, harvested from four dogs, [...] Read more.
Background/Objectives: This study aimed to evaluate the regenerative potential of autologous concentrated growth factor (CGF) combined with residual pulp tissue in immature dog teeth using a histological and histomorphometric analysis. Materials and Methods: Thirty immature anterior and premolar teeth, harvested from four dogs, were randomly assigned to three groups (n = 10 each): group I (negative control, untreated teeth), group II (positive control, complete pulp removal with blood clot in the canal), and group III (experimental, partial pulp removal with 1–4 mm residual pulp and placement of autologous CGF). After 1 and 3 months, animals were euthanized, and samples were processed for histological and histomorphometric assessments. Results: The CGF-treated group exhibited newly formed tissue with morphological characteristics comparable to the negative control group after partial pulp removal. Conclusions: The combination of CGF with 1–4 mm of residual pulp was associated with enhanced tissue organization, representing a promising approach for dentin–pulp complex (DPC) regeneration within this experimental context. Full article
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24 pages, 2038 KB  
Article
Evaluating the Managerial Feasibility of an AI-Based Tooth-Percussion Signal Screening Concept for Dental Caries: An In Silico Study
by Stefan Lucian Burlea, Călin Gheorghe Buzea, Irina Nica, Florin Nedeff, Diana Mirila, Valentin Nedeff, Lacramioara Ochiuz, Lucian Dobreci, Maricel Agop and Ioana Rudnic
Diagnostics 2026, 16(4), 638; https://doi.org/10.3390/diagnostics16040638 - 22 Feb 2026
Viewed by 494
Abstract
Background: Early detection of dental caries is essential for effective oral health management. Current diagnostic workflows rely heavily on radiographic imaging, which involves infrastructure requirements, workflow coordination, and resource considerations that may limit frequent use in high-throughput or resource-constrained settings. These contextual factors [...] Read more.
Background: Early detection of dental caries is essential for effective oral health management. Current diagnostic workflows rely heavily on radiographic imaging, which involves infrastructure requirements, workflow coordination, and resource considerations that may limit frequent use in high-throughput or resource-constrained settings. These contextual factors motivate exploration of adjunct screening concepts that could support front-end triage decisions within existing care pathways. This study evaluates, in simulation, whether modeled tooth-percussion response signals contain sufficient discriminative information to justify further translational and managerial investigation. Implementation costs, workflow optimization, and economic outcomes are not evaluated directly; rather, the objective is to assess whether the technical preconditions for a potentially scalable screening concept are satisfied under controlled in silico conditions. Methods: An in silico model of tooth percussion was developed in which enamel, dentin, and pulp/root structures were represented as a simplified layered mechanical system. Impulse responses generated from simulated tapping were used to compute the modeled surface-vibration response (enamel-layer displacement), which served as a proxy for a measurable percussion-related signal (e.g., contact vibration), rather than a recorded acoustic waveform. Carious conditions were simulated through depth-dependent reductions in stiffness and effective mass and increases in damping to represent enamel and dentin demineralization. A synthetic dataset of labeled simulated signals was generated under varying structural parameters and measurement-noise assumptions. Machine-learning models using Mel-frequency cepstral coefficient (MFCC) features were trained to classify healthy teeth, enamel caries, and dentin caries at a screening (triage) level. Results: Under baseline simulation conditions, the classifier achieved an overall accuracy of 0.97 with balanced macro-averaged F1-score (0.97). Misclassifications occurred primarily between healthy and enamel-caries categories, whereas dentin-caries cases were most consistently identified. When measurement noise and structural variability were increased, performance declined gradually, reaching approximately 0.90 accuracy under the most challenging simulated scenario. These results indicate that discriminative information is present within the modeled signals at a screening (triage) level, meaning that higher-risk categories can be distinguished probabilistically rather than with definitive diagnostic certainty. Sensitivity and specificity trade-offs were not optimized in this study, as the objective was to assess separability rather than to define clinical decision thresholds. Conclusions: Within the constraints of the in silico model, simulated tooth-percussion response signals demonstrated discriminative patterns between healthy, enamel caries, and dentin caries categories at a screening (triage) level. These findings establish technical plausibility under controlled simulation conditions and support further investigation of percussion-based screening as a potential adjunct to clinical assessment. From a healthcare management perspective, the present results address a prerequisite question—whether such signals contain sufficient information to justify translational research, rather than demonstrating workflow optimization, cost reduction, or system-level impact. Clinical validation, threshold optimization, and implementation studies are required before managerial or operational benefits can be evaluated. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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38 pages, 779 KB  
Review
Pulp–Dentin Regeneration via Cell Homing: Current Evidence and Perspectives on Cell-Free Regenerative Endodontic Therapy
by Michele Beco, Francesca Di Pasquale, Chiara Valenti, Paolo Betti, Gian Luca Mascolo, Lorella Marinucci, Stefano Eramo and Stefano Pagano
Medicina 2026, 62(2), 375; https://doi.org/10.3390/medicina62020375 - 13 Feb 2026
Viewed by 589
Abstract
Background and Objectives: The regeneration of the pulp–dentin complex represents an alternative to conventional root canal treatment, aiming to preserve tooth biology and function. Cell-free regenerative endodontic therapy (CF-RET) exploits endogenous stem cells from the periapical region without ex vivo cell manipulation. [...] Read more.
Background and Objectives: The regeneration of the pulp–dentin complex represents an alternative to conventional root canal treatment, aiming to preserve tooth biology and function. Cell-free regenerative endodontic therapy (CF-RET) exploits endogenous stem cells from the periapical region without ex vivo cell manipulation. Despite growing interest, the biological mechanisms, clinical indications, and predictability of CF-RET remain not clearly defined. This structured narrative review aimed to update a previous review by analyzing recent human studies on CF-RET. Materials and Methods: This review was conducted using the PRISMA 2020 guidelines to guide transparent reporting of the literature search and study selection process and was registered in PROSPERO (CRD420251075131). In vitro and in vivo human studies published between January 2017 and December 2024 investigating CF-RET were included, while studies involving cell transplantation, non-human models, case reports, and reviews were excluded. Study selection, data extraction, and quality assessment using the QuADS tool were performed, and the evidence was synthesized using a qualitative narrative approach. Results: Sixty-four studies were included. In vitro studies reported favorable effects of growth factors, exosomes, and biomimetic scaffolds on stem cell viability, migration, proliferation, odontogenic differentiation, and angiogenesis, while neurogenic differentiation was less consistently investigated. Scaffold composition, microstructure, and rheological properties were also considered. In vivo studies mainly focused on immature teeth with incomplete root development and demonstrated positive clinical and radiographic outcomes, including root development and canal diameter reduction. Conclusions: The current evidence supports the biological potential of CF-RET as a regenerative approach; however, substantial heterogeneity, the limited number of clinical studies and the absence of standardized protocols preclude definitive conclusions, highlighting the need for further well-designed translational and clinical investigations considering clinical applicability. Full article
(This article belongs to the Section Dentistry and Oral Health)
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19 pages, 6042 KB  
Article
Impact of Taper Design on Cleaning Efficacy, Stress Generation, and Irrigant Performance: A Combined Experimental, Finite Element Analysis, and Computational Fluid Dynamics Assessment
by Celia Vinuesa Maqueda, Natalia Navarrete, Ana Ramírez-Muñoz, Ana Martín-Díaz, César de Gregorio, José Aranguren, Giulia Malvicini, Simone Grandini, Gaya C. S. Vieira and Alejandro R. Pérez
Dent. J. 2026, 14(2), 108; https://doi.org/10.3390/dj14020108 - 13 Feb 2026
Viewed by 349
Abstract
Background/Objectives: This study aimed to compare the cleaning efficacy, biomechanical stress distribution under simulated occlusal loading after instrumentation, and irrigant dynamics of three NiTi rotary systems, namely ProTaper Gold, TruNatomy, and SlimShaper, using a combined experimental, finite element analysis (FEA), and computational fluid [...] Read more.
Background/Objectives: This study aimed to compare the cleaning efficacy, biomechanical stress distribution under simulated occlusal loading after instrumentation, and irrigant dynamics of three NiTi rotary systems, namely ProTaper Gold, TruNatomy, and SlimShaper, using a combined experimental, finite element analysis (FEA), and computational fluid dynamics (CFD) approach. Methods: Transparent 3D replicas of mandibular mesial roots filled with a gel-like pulp tissue were instrumented with the three systems (n = 13 per group). Standardized irrigation was performed with 4% NaOCl delivered through IrriFlex® needles positioned 2 mm from the working length. Cleaning effectiveness was assessed through digital image analysis, FEA simulation of occlusal loading, and CFD evaluation of irrigation flow, wall shear stress, and dynamic pressure. Results: All systems left residual tissue, with no statistically significant differences in cleaning efficacy among them (p > 0.05). Descriptively, ProTaper Gold showed the lowest mean residual tissue (0.15 ± 0.25%), followed by SlimShaper (2.50 ± 3.81%) and TruNatomy (4.20 ± 5.12%). CFD revealed that ProTaper Gold generated the highest irrigant velocities and wall shear stresses, while SlimShaper showed the highest dynamic pressure. FEA indicated that ProTaper Gold produced the highest stress concentrations, especially in the pericervical dentin, whereas TruNatomy and SlimShaper preserved more dentin. Conclusions: Cleaning efficacy was comparable across systems. CFD/FEA from representative models illustrated patterns of irrigant dynamics and dentin preservation without supporting system superiority. Full article
(This article belongs to the Special Issue Endodontics and Restorative Sciences: 2nd Edition)
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16 pages, 483 KB  
Systematic Review
Minimally Invasive Chemomechanical Caries Removal in Paediatric Dentistry: A Systematic Review of Papacarie and Brix 3000
by María Carmona-Santamaría, Davinia Pérez-Sánchez, Juan Ignacio Aura-Tormos, Clara Guinot-Barona, Laura Marqués-Martínez and Esther García-Miralles
J. Clin. Med. 2026, 15(4), 1367; https://doi.org/10.3390/jcm15041367 - 9 Feb 2026
Cited by 1 | Viewed by 495
Abstract
Background/Objectives: Dental caries is one of the most prevalent chronic diseases in childhood. Rotary bur handpiece excavation has been the standardised mechanical benchmark for infected dentine removal in the primary dentition, but it is associated with noise, vibration, and nociceptive triggers that influence [...] Read more.
Background/Objectives: Dental caries is one of the most prevalent chronic diseases in childhood. Rotary bur handpiece excavation has been the standardised mechanical benchmark for infected dentine removal in the primary dentition, but it is associated with noise, vibration, and nociceptive triggers that influence behavioural cooperation in paediatric patients. CMCR gels have been developed for selective softening and excavation of infected primary dentine without macroscopic removal of adjacent sound tissue at the protocol-defined site. The objective of this review was to systematically synthesise the evidence on chemomechanical caries removal (CMCR) using Papacarie or Brix 3000 compared with infected dentine excavation using rotary bur handpiece instrumentation in the primary (deciduous) dentition, focusing on excavation effectiveness, paediatric procedural tolerance, anaesthetic requirement, dentine surface morphology at the excavation interface, and protocol-level operative duration per primary molar. Methods: A systematic search was performed in PubMed, Web of Science, and Scopus for English-language studies from database inception to 31 December 2023. Although no eligible paediatric dental records addressing CMCR gels for excavation of infected primary dentine were identified before 2009, the earlier literature was not intentionally excluded; rather, it did not retrieve topic-specific matches meeting the eligibility criteria. Clinical and in vitro investigations evaluating CMCR gels (Papacarie or Brix 3000) for excavation of infected primary dentine in primary molars were eligible. Outcomes were aggregated qualitatively by excavation approach and reported per primary molar at the individual study protocol level. Quantitative pooling or meta-analysis was not conducted due to heterogeneity in study designs and lack of unified denominators across the included literature. Results: Fifteen studies were included (randomised clinical trials, observational clinical investigations, clinical comparative studies, and in vitro assessments) evaluating infected dentine excavation in primary molars. CMCR gels achieved successful excavation of infected primary dentine with dentine preservation at the adjacent non-infected interface without macroscopic loss of sound tissue. Individual study protocols that reported paediatric pain outcomes during primary-molar excavation registered lower pain scores, reduced acoustic/vibratory stress, lower anaesthetic escalation cycles, and decreased local anaesthesia requirement per primary molar compared with rotary bur handpiece excavation arms. Dentine surfaces analysed under SEM protocols at the infected excavation interface described patent tubules, absence of compacted smear at the interface, preserved intertubular dentine, and no iatrogenic gouging or macrofracture of non-infected primary dentine per molar at the individual study level. Operative duration for CMCR ranged from 10 to 25 min per primary molar per tooth, while rotary bur handpiece excavation required 3–10 min per primary molar per tooth, depending on cavity extension and dentine hardness, as defined by each study protocol. Microleakage and bond-strength assays performed in vitro at the individual protocol level did not register disadvantage signals traceable to adhesive or sealing incompatibility following CMCR gel excavation per primary molar. Conclusions: CMCR with Papacarie or Brix 3000 enables protocol-level selective excavation of infected primary dentine in primary molars, reducing acoustic, vibratory, and nociceptive triggers that influence behaviour and local anaesthetic requirement per primary molar. Clinical inference should be restricted to infected dentine excavation per primary-molar denominators, avoiding extrapolation to all caries depths or all deciduous-tooth types. Standardised paediatric primary-molar infected dentine excavation trials with homogeneous denominators, bias-controlled outcome instruments, and longitudinal follow-up are required to strengthen cavity-depth indications, pulp-proximal excavation reliability, and restorative longevity guidance in the primary dentition clinical workflow. Full article
(This article belongs to the Special Issue Oral Health in Children: Clinical Management)
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20 pages, 741 KB  
Systematic Review
Histological Tissue Response to Calcium Silicate-Based Cements Assessed in Human Tooth Culture Models: A Systematic Review
by Alberto Cabrera-Fernández, Hebertt Gonzaga dos Santos Chaves, Aránzazu Díaz-Cuenca, Juan J. Segura-Egea, Jenifer Martín-González, João Peça, Diana B. Sequeira and João Miguel Marques dos Santos
J. Funct. Biomater. 2026, 17(2), 78; https://doi.org/10.3390/jfb17020078 - 6 Feb 2026
Viewed by 1097
Abstract
Ex vivo human tooth culture models preserve the native dentine–pulp complex and offer a translational platform to study pulp-capping biomaterials. This systematic review aimed to synthesize the evidence on histological pulp tissue responses to calcium silicate-based cement (CSCs) used for direct pulp capping [...] Read more.
Ex vivo human tooth culture models preserve the native dentine–pulp complex and offer a translational platform to study pulp-capping biomaterials. This systematic review aimed to synthesize the evidence on histological pulp tissue responses to calcium silicate-based cement (CSCs) used for direct pulp capping in human tooth culture models. The review followed PRISMA 2020 guidance. Eligible studies were ex vivo whole human tooth culture models with direct pulp exposure treated with commercial or experimental CSCs and reporting histological outcomes. Risk of bias was assessed using the QUIN tool. Thirteen studies were included. Most used immature human third molars (from 15- to 19-year-old patients) and culture periods up to 28 days, with a minority extending observation to 45–90 days. Across hydraulic CSCs, Biodentine was the most frequently evaluated material, followed by ProRoot MTA and several experimental hydraulic and resin-modified formulations. Overall, hydraulic CSCs were consistently associated with biocompatible pulp responses and a pro-mineralization pattern characterized by periexposure mineralized foci/osteodentin-like tissue; where assessed, immunohistochemistry supported odontoblast-like differentiation. In contrast, the resin-modified CSC TheraCal LC and other experimental resin-modified CSCs showed more heterogeneous findings, with reports of absent, delayed, or less prominent mineralization compared with reference hydraulic CSCs. In intact human tooth culture models, hydraulic CSCs show reproducible biocompatibility and early mineralization features consistent with reparative dentinogenesis, whereas resin-modified CSCs demonstrate more variable histological performance. Full article
(This article belongs to the Special Issue The 15th Anniversary of JFB—Endodontic Biomaterials)
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21 pages, 29521 KB  
Article
Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications
by Mohammad Alenizy, Abdullah Alhussein, Nader Almutairi, Ibrahim Ba-Armah, Heba Alqarni, Yazeed Altamimi, Ayman Altamimi, Tao Ma, Man-Kyo Chung, Michael D. Weir, Abraham Schneider and Hockin H. K. Xu
Materials 2026, 19(3), 487; https://doi.org/10.3390/ma19030487 - 26 Jan 2026
Viewed by 479
Abstract
Metformin is a promising small molecule for dentin regeneration, but an effective local delivery system for pulp applications has been underexplored. This study encapsulated metformin in poly(lactic-co-glycolic acid) (PLGA) microspheres and incorporated them into calcium phosphate–chitosan cement (CPCC) as a direct pulp-capping material [...] Read more.
Metformin is a promising small molecule for dentin regeneration, but an effective local delivery system for pulp applications has been underexplored. This study encapsulated metformin in poly(lactic-co-glycolic acid) (PLGA) microspheres and incorporated them into calcium phosphate–chitosan cement (CPCC) as a direct pulp-capping material (DPC). Metformin-PLGA microspheres were prepared by double emulsion and mixed with CPCC at a concentration of 0% to 20% by weight. Microsphere morphology, encapsulation efficiency, chemical composition, and physico-mechanical properties were characterized, and compatibility with human dental pulp stem cells (hDPSCs) was evaluated by live/dead assay and SEM. The microspheres were spherical (5.43 ± 0.17 µm) with (51 ± 3.69%) encapsulation efficiency, and FTIR confirmed metformin incorporation. The 15% Met-PLGA-CPCC group showed flexural strength (15.22 ± 1.98 MPa), elastic modulus (4.60 ± 0.73 GPa), and work of fracture (104.96 ± 12.48 J/m2) comparable to or higher than CPCC and MTA, while all Met-PLGA-CPCC groups had shorter setting times ranging from 18 min to 27 min than CPCC (39.15 ± 2.10 min) and MTA (123 ± 4.2 min). Metformin release increased proportionally with Met-PLGA content. hDPSCs exhibited good attachment and high viability on all materials over the evaluated period. In conclusion, Met-PLGA-CPCC provides fast-setting and favorable physico-mechanical properties, sustained metformin delivery, and excellent hDPSC compatibility. These properties support its potential as a bioactive direct pulp-capping material and as a versatile platform for regenerative applications. Full article
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16 pages, 4573 KB  
Article
Odontoblasts in Equine Hypsodont Teeth—How They Cope with Permanent Occlusal Wear
by Laura Beate Heilen, Jessica Roßgardt, Jutta Dern-Wieloch, Jörg Vogelsberg and Carsten Staszyk
Animals 2026, 16(2), 341; https://doi.org/10.3390/ani16020341 - 22 Jan 2026
Viewed by 628
Abstract
Horses’ hypsodont (high-crowned) teeth face permanent dental wear. This is compensated for by a continuous eruption, which requires a high adaptability of odontoblasts; otherwise, the dental pulp would be exposed. Here, we report on how equine odontoblasts respond to the challenge of maintaining [...] Read more.
Horses’ hypsodont (high-crowned) teeth face permanent dental wear. This is compensated for by a continuous eruption, which requires a high adaptability of odontoblasts; otherwise, the dental pulp would be exposed. Here, we report on how equine odontoblasts respond to the challenge of maintaining a high production rate of dentin. We analyzed CD90, a marker of odontoblastic differentiation, and nestin, a marker of mature odontoblasts, in equine pulpal tissue via immunofluorescence. For comparison, we examined the hypselodont (ever-growing) incisors and brachydont (short-crowned) molars of rats. Immunofluorescence and Western blot analysis of pulpal tissue revealed a higher content of CD90-positive cells in hypsodont equine teeth than in brachydont and hypselodont rat teeth. The odontoblastic layer of hypsodont teeth was positive for CD90 (marker for differentiating odontoblasts), which was not the case for brachydont and hypselodont rat teeth. Most samples of hypsodont teeth were negative for nestin, whereas in hypselodont and brachydont teeth, odontoblasts were positive for nestin (marker for mature odontoblasts). Our findings suggest that there is a constant replacement of odontoblasts in the equine dentition, enabling a continuous high production rate of dentin. These results contradict the idea of lifelong vital, postmitotic and productive odontoblasts. Full article
(This article belongs to the Section Equids)
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10 pages, 951 KB  
Case Report
Direct Pulp Capping of Dental Pulp with Two Different Autologous Platelet Concentrates A-PRF+ and H-PRF—A Report on Two Cases
by Janet Kirilova and Dimitar Yovchev
Dent. J. 2026, 14(1), 48; https://doi.org/10.3390/dj14010048 - 12 Jan 2026
Viewed by 571
Abstract
Background: Autologous platelet concentrates, including platelet-rich fibrin (PRF) matrices, have been proposed as biologically active scaffolds for vital pulp therapy. Evidence on the clinical use of different solid PRF matrices for direct pulp capping remains limited. Objective: The aim of this [...] Read more.
Background: Autologous platelet concentrates, including platelet-rich fibrin (PRF) matrices, have been proposed as biologically active scaffolds for vital pulp therapy. Evidence on the clinical use of different solid PRF matrices for direct pulp capping remains limited. Objective: The aim of this study is to describe and monitor two clinical cases of reversible pulpitis treated with direct pulp capping using two PRF membranes prepared by different centrifugation approaches, namely advanced platelet-rich fibrin plus (A-PRF+) and horizontal platelet-rich fibrin plus (H-PRF). Methods: In Case 1, A-PRF+ was prepared using a fixed-angle centrifugation protocol; in Case 2, H-PRF was prepared using a horizontal centrifugation protocol. In both cases, deep carious lesions with small carious pulp exposures (<1.5 mm) were managed by caries removal, ozone-assisted dentin disinfection, and direct pulp capping with the respective PRF membrane, followed by temporary calcium-silicate cement definitive coronal restoration. Clinical and radiographic follow-up, including cone-beam computed tomography, was performed for up to 12 months. Results: In Case 1 (A-PRF+), reparative dentin bridge formation was confirmed at 90 days, with a thickness of 0.2 mm. In Case 2 (H-PRF), reparative dentin was observed within 46 days, with a thickness of 0.28 mm. In both cases, pulp vitality was maintained, and no clinical symptoms or periapical changes were detected during the 12-month follow-up. Conclusions: These two cases suggest that direct pulp capping using PRF membranes (A-PRF+ or H-PRF), combined with ozone-assisted dentin disinfection and adequate coronal sealing, may be associated with maintained pulp vitality and hard-tissue repair after carious pulp exposure diagnosed as reversible pulpitis. Due to the descriptive two-case design and major confounding factors (including age and lesion characteristics), no comparative conclusions can be drawn. Prospective controlled clinical studies with standardized protocols are warranted. Full article
(This article belongs to the Special Issue Regenerative Dentistry: Innovations and Clinical Applications)
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26 pages, 2695 KB  
Systematic Review
Clinical and Radiographic Outcomes of Vital Pulp Therapy Using Resin-Modified Versus Conventional Calcium Silicate-Based Materials: A Systematic Review and Meta-Analysis
by Alberto Cabrera-Fernández, Laura Dominguez-Dominguez, Antonio Pérez-Pérez, João Miguel Marques Santos, Aránzazu Díaz-Cuenca, Daniel Torres-Lagares, Diana B. Sequeira, Juan J. Segura-Egea and Jenifer Martín-González
J. Funct. Biomater. 2026, 17(1), 32; https://doi.org/10.3390/jfb17010032 - 7 Jan 2026
Cited by 2 | Viewed by 1003
Abstract
Vital pulp therapy (VPT) is increasingly recognised as a biologically driven alternative to root canal treatment in teeth with deep caries and a vital pulp diagnosis. Resin-modified calcium silicate-based materials (RM-CSMs) were introduced to combine the bioactivity of traditional cements with improved handling [...] Read more.
Vital pulp therapy (VPT) is increasingly recognised as a biologically driven alternative to root canal treatment in teeth with deep caries and a vital pulp diagnosis. Resin-modified calcium silicate-based materials (RM-CSMs) were introduced to combine the bioactivity of traditional cements with improved handling and immediate light-curing, but their biological performance remains debated. Objectives: This systematic review and meta-analysis aimed to evaluate the clinical and radiographic outcomes of VPT performed with RM-CSMs compared with conventional non-resin-modified calcium silicate-based materials (NRM-CSMs) Methods: PRISMA Guidelines were followed to carry out this systematic review. Electronic databases (Medline, Embase, Scopus, and Web of Science) were searched up to October 2025 for randomised clinical trials evaluating indirect pulp capping, direct pulp capping, or pulpotomy. Nine trials met the inclusion criteria. Meta-analyses were performed for TheraCal LC, the only RM-CSM with sufficient clinical evidence. The risk of bias was assessed using the RoB 2 Tool. The certainty of evidence was assessed using GRADE. Results: Pooled results showed no significant differences in overall clinical–radiographic success between RM-CSMs and NRM-CSMs at 90 or 180 days. At 360 days, a trend favouring NRM-CSMs emerged, though not statistically significant. Dentine bridge formation at 360 days was significantly lower with TheraCal LC. Conclusions: Current RM-CSMs demonstrate comparable short-term success to conventional materials but still present biological limitations, particularly regarding long-term reparative outcomes. NRM-CSMs remain the preferred option when maximal bioactivity and predictable dentinogenesis are required Full article
(This article belongs to the Special Issue Advanced Materials for Clinical Endodontic Applications (3rd Edition))
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39 pages, 2194 KB  
Review
Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain
by Man-Kyo Chung, Swarnalakshmi Raman and Arpad Szallasi
Int. J. Mol. Sci. 2026, 27(1), 182; https://doi.org/10.3390/ijms27010182 - 23 Dec 2025
Viewed by 1569
Abstract
Dental pain often arises from the compromised integrity of the tooth pulp due to dental injury or caries. The dentin–pulp complex has long been considered to be central to the unique biology of dental pain. Most trigeminal ganglion afferents projecting into tooth pulp [...] Read more.
Dental pain often arises from the compromised integrity of the tooth pulp due to dental injury or caries. The dentin–pulp complex has long been considered to be central to the unique biology of dental pain. Most trigeminal ganglion afferents projecting into tooth pulp are myelinated neurons, which lose their myelination at the site of peripheral dentin innervation. The pulpal afferents likely combine multiple internal and external stimuli to mediate nociception and maintain pulp homeostasis. Transient receptor potential (TRP) ion channels in neurons and odontoblasts, along with mechanosensitive ion channels such as Piezo, form a key molecular hub for pulpal nociception by sensing thermal, chemical, and hydrodynamic stimuli. Among these, TRP vanilloid 1 (TRPV1) mediates nociception and the release of calcitonin-gene-related peptides (CGRPs), while TRP canonical 5 (TRPC5) mediates cold pain. TRP melastatin 8 (TRPM8) mediates the transduction of hyperosmotic stimuli. Pulpitis elevates endogenous TRPV1 and TRPA1 agonists, while inflammatory mediators sensitize TRP channels, amplifying pain. CGRP recruits immune cells and promotes bacterial clearance and reparative dentinogenesis, yet the roles of TRP channels in these processes remain unclear. Future studies should use advanced multi-omics and in vivo or organotypic models in animal and human teeth to define TRP channel contributions to pain, immune responses, and regeneration. Understanding neuronal and non-neuronal TRP channel interactions and their integration with other ion channels may enable novel analgesic and regenerative strategies in dentistry. Full article
(This article belongs to the Special Issue TRP Channels for Pain, Itch and Inflammation Relief: 2nd Edition)
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