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Introduction: Eradication of residual biofilm from root canal dentine is critical for the success of regenerative endodontic procedures (REPs). The aim of the study: To evaluate the influence of ultrasonically activated irrigants in concentrations used for REPs for removal of dual-species biofilm from three-dimensionally printed tooth models with attached dentine samples. Methodology: Seventy-two three-dimensionally printed teeth models were fabricated with a standardized slot in the apical third of the root to ensure a precise fit with a human root dentine specimen. Dual-species biofilms (comprising Enterococcus faecalis and Streptococcus mutans) were cultivated in the root canal for a period of three weeks. Models with dentine specimens were randomly assigned into 5 groups according to the irrigation protocol; G1(dis H2O): infected root canals irrigated with distilled water to serve as controls; G2(1.5% NaOCl): 1.5% NaOCl for five minutes; G3(1.5% NaOCl + PUI): 1.5% NaOCl + passive ultrasonic irrigation (PUI) for 30 s; G4(3% NaOCl): 3% NaOCl for five minutes; G5(3% NaOCl + PUI): 3% NaOCl + PUI for 30 s. Bacterial reduction was determined by colony-forming unit (CFU) counting (n = 12/G), whilst biofilms were analyzed using field emission scanning electron microscopy in additional samples. Results: The four experimental groups showed a significant reduction in CFU counts compared to the control group (p < 0.05). When compared with (dis H2O), the highest reduction in bacterial count was obtained in G5 (3% NaOCl + PUI) followed by G4 (3% NaOCl), then G3 (1.5% NaOCl + PUI), and finally G2 (1.5% NaOCl). Conclusion: Results of the current study propose that a 3D-printed mature tooth model can be effectively used to analyze the antimicrobial effects of different irrigation protocols on dual-species biofilm. The use of NaOCl in concentrations used for regenerative endodontics can effectively remove bacterial biofilms. Furthermore, the use of PUI did not significantly enhance antibacterial effects of NaOCl. [ABSTRACT FROM AUTHOR]

To investigate the apical extrusion of sodium hypochlorite in immature permanent teeth caused by conventional syringe irrigation (CSI), EDDY, XP-endo Finisher file (XP-F), and a new laser irrigation activation system [shock-wave-enhanced-emission-photo-acoustic-streaming (SWEEPS)]. Three-dimensionally printed forty-nine teeth with immature central incisor morphology were randomly assigned to seven experimental groups, based on the irrigation activation methods and insertion depths (1 mm and 2 mm short of the working length) as follows: CSI-1, CSI-2, EDDY-1, EDDY-2, XP-1, XP-2, and SWEEPS. Prior to the irrigation activation process, samples were placed in metacresol mixed agar gel in Eppendorf tubes. To evaluate NaOCI extrusion into the gel, each sample was digitally photographed, and the area of apical extrusion was analyzed using ImageJ software. To examine potential significant differences between the continuous variables, the Mann–Whitney U test and Kruskal–Wallis H test, were applied (P =.05). The SWEEPS resulted in a greater amount of apical extrusion compared to the CSI method, regardless of the insertion depth (P < 0.001). The SWEEPS resulted in greater apical extrusion scores compared to EDDY-2 (P < 0.001). The EDDY-1 resulted in greater amount of apical extrusion scores compared to EDDY-2 (P < 0.001). This study, the first to show the effect of the novel SWEEPS technology on NaOCI extrusion, found that irrigation activation can cause different levels of apical extrusion depending on the method and distance from the working length. It is crucial to consider the potential occurrence of apical extrusion when applying activation methods to immature teeth. [ABSTRACT FROM AUTHOR]

The dehydrated human amnion–chorion membranes (dHACMs) derived from the human placenta have emerged as a promising biomaterial for dental pulp regeneration owing to their unique biological and structural properties. The purpose of this review is to explore the potentials of dHACMs in dental pulp tissue engineering, focusing on their ability to promote cellular proliferation, differentiation, angiogenesis, and neurogenesis. dHACMs are rich in extracellular matrix proteins and growth factors such as TGF-β1, FGF2, and VEGF. They also exhibit significant anti-inflammatory and antimicrobial properties, creating an optimal environment for dental pulp regeneration. The applications of dHACMs in regenerative endodontic procedures are discussed, highlighting their ability to support the formation of dentin and well-vascularized pulp-like tissue. This review demonstrates that dHACMs hold significant potential for enhancing the success of pulp regeneration and offer a biologically based approach to preserve tooth vitality and improve tooth survival. Future research is expected to focus on conducting long-term clinical studies to establish their efficacy and safety. [ABSTRACT FROM AUTHOR]

External inflammatory root resorption (EIRR) is a significant complication that can occur following traumatic dental injuries, with a prevalence of approximately 18%. Most cases occur during the early stage of the mixed dentition. Specifically, EIRR occurs in approximately 5%–8% of luxation injuries, 30% of replanted teeth following avulsion, and 38% of intruded teeth. Conventional methods for addressing EIRR in immature teeth pose several challenges. This often requires numerous dental visits where Ledermix and calcium hydroxide are used, which may significantly prolong the treatment. Additionally, the effect of prolonged use of calcium hydroxide medication in the root canal is debatable. Recent publications have highlighted the ability of regenerative endodontic treatment (RET) to effectively stop and repair EIRR in a relatively brief time, yielding impressive results. Nevertheless, the underlying mechanism responsible for this effect remains unclear. A hypothesis is proposed and drawn from existing data, explaining the mechanism by which RET triggers alterations in the root dimensions of necrotic immature teeth, facilitating continuous root maturation. The hypothesis suggests that bioactive molecules, including growth factors, might be able to penetrate the denuded dentin, reach the resorbed area, and attract stem cells from the surrounding periodontal ligament and adjacent bone, leading to the arrest of the resorption process. This recruitment may trigger repair mechanisms, ultimately resulting in the coverage of the denuded dentin with a new layer of periodontal ligament, cementoid, and cementum. A hypothesis of the potential mechanism in which RET may arrest EIRR is presented along with a case report. [ABSTRACT FROM AUTHOR]

Recognizing the necessity of novel disinfection strategies for improved bacterial control to ultimately favor tissue regeneration, this study developed and characterized antibiotics-laden silk fibroin methacrylated (SilkMA) scaffolds for regenerative endodontics. SilkMA-based solutions (10% w/v) containing Clindamycin (CLI) or Tinidazole (TIN) (0 – control; 5, 10, or 15% w/w) or the combination of both drugs (BiMix CLI/TIN 10%) were electrospun and photocrosslinked. Morphology and composition were assessed using scanning electron microscopy and Fourier-transform infrared spectroscopy. Additionally, swelling and degradation profiles were also determined. Cytotoxicity was evaluated in stem cells from apical papilla. Antibacterial efficacy was tested using direct and indirect contact assays against Aggregatibacter actinomycetemcomitans / Aa , Actinomyces naeslundii / An , Enterococcus faecalis / Ef, and Fusobacterium nucleatum / Fn. E. faecalis biofilm inhibition on dentin discs was specifically evaluated for BiMix-laden scaffolds. Data were statistically analyzed with a significance level of 5%. Scanning electron microscopy revealed that all scaffolds had similar characteristics, including fiber morphology and bead absence. Fourier-transform infrared spectroscopy showed the incorporation of CLI and TIN into the fibers and in BiMix scaffolds. Antibiotic-laden scaffolds exhibited lower swelling capacity than the control and were degraded entirely after 45 days. Scaffolds laden with CLI, TIN, or BiMix throughout all time points did not reduce stem cells from apical papilla's viability. CLI-laden scaffolds inhibited the growth of Aa , An , and Ef , while TIN-laden scaffolds inhibited Fn growth. BiMix-laden scaffolds significantly inhibited Aa , An , Ef , and Fn in direct contact, and their aliquots inhibited An and Fn through indirect contact, with additional biofilm inhibition against Ef. BiMix-laden SilkMA scaffolds are cytocompatible and exhibit antimicrobial effects against endodontic pathogens, indicating their therapeutic potential as a drug delivery system for regenerative endodontics. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to compare the application of three types of normal scaffolds—native chitosan, enzymatically modified chitosan, and blood clot (BC)—on pulp regeneration in the teeth of experimental dogs through histological examination, to determine the quantity and type of new tissues formed within the root canal. Materials and Methods: The research sample consisted of 32 root canals from 20 premolars of two male local experimental dogs. The sample was randomly divided into a control group, in which no intervention was performed on the teeth, and three experimental groups based on the type of scaffold used: the BC group, the native chitosan combined with BC (NCS + BC) group, and the enzymatically modified chitosan combined with BC (EMCS + BC) group. Mechanical and chemical cleaning of the canals was performed, followed by the application of the studied scaffolds within the root canals. After 3 months, the teeth were extracted and prepared for histological study, where two variables were studied: the percentage of total vital tissue (soft and hard; VT%) and the percentage of soft vital tissue only (ST%). A one‐way ANOVA and Bonferroni tests were used to determine significant differences between the groups at a 95% confidence level. Results: The VT% values were significantly higher in the EMCS + BC group compared to both the NCS + BC and BC groups. The ST% values were also significantly higher in the EMCS + BC group compared to the BC group. However, no significant differences in ST% values were observed between the NCS + BC group and either the BC or EMCS + BC groups. Conclusions: Within the limitations of this study, we conclude that the application of enzymatically modified chitosan scaffolds combined with BC yields superior results in pulp regeneration, which contributes to the formation of pulp‐like tissue and cells resembling odontoblasts, as well as apex closure with tissue resembling bone tissue. [ABSTRACT FROM AUTHOR]

Context: Regenerative endodontic procedures allow continued root development, but open apices limit mechanical debridement which implores the need for an effective and potent intracanal medicament to disinfect the canal space. Aim: This study aimed to assess the effect of nanobubble (NB) water on dentinal penetration of intracanal medicaments in simulated immature teeth. Materials and Methods: A total of 60 freshly extracted mandibular premolars were prepared to simulate blunderbuss canals. Canals were irrigated with 5.25% NaOCl and 17% ethylenediaminetetraacetic acid by a final rinse of saline. Teeth were divided into 3 groups with different medicaments which were further subdivided into two subgroups with saline and NB water as vehicle, respectively. The longitudinal sections of teeth were evaluated using stereomicroscopy. Statistical Analysis Used: Two-way ANOVA and Tukey's post hoc test were used. Results: The results indicated that samples with NB water as vehicle showed better penetration than their counterparts that were carried with saline. The highest penetration was seen in the middle third of the root. Conclusions: It could be concluded that NB water enhanced the dentinal penetration of all antimicrobial agents and calcium hypochlorite with NB water showed maximum penetration depth. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusion Regenerative endodontic procedures (REPs) are tissue engineering‐based treatments aimed at regenerating the pulp‐dentin complex. However, these procedures are not widely practiced or well‐known among dentists due to a lack of training. This study aims to develop a practical hands‐on training model for REPs to enhance students' theoretical knowledge and practical skills.A cost‐effective, easy‐to‐operate, and reusable training model for preclinical training of REPs was developed. A total of 125 undergraduates were divided into an experimental group (REPs model) and a control group (traditional teaching). The students' theoretical knowledge and operational skills were assessed through examinations and practical assessments. Student perceptions were assessed by questionnaires.The experimental group achieved higher scores in theoretical knowledge and operational skills compared to the control group (p < .001). The process evaluation of the experimental group demonstrated a high level of proficiency in executing root canal disinfection steps, with pass rates ranging from 93.5% to 95.2%. Students in both groups perceived the model as valuable for improving critical thinking, stimulating interest, and enhancing their confidence and proficiency.The developed REPs training model is a practical and effective tool for teaching and training regenerative endodontics. It bridges the gap between preclinical and clinical education, enhancing students' confidence and clinical competence. [ABSTRACT FROM AUTHOR]

Studies on the clinical outcomes and prognostic factors of regenerative endodontic procedures (REPs) in a large population and long-term recall period have been limited. Therefore, the aims of this study were to evaluate treatment outcomes and prognostic factors of REPs. Immature permanent teeth treated with REPs with a minimum one-year follow-up period were included. Treatment outcomes (functional retention, healed rate, root development, and sensibility test response) and any prognostic factors were analyzed with multivariable Cox regression, linear regression, and modified Poisson regression. One-hundred-twenty REPs teeth with a mean 41.7-month recall period were included with a functional retention rate of 97.5%. The healed, healing, and diseased rates of REPs were 80%, 9.2%, and 10.8%, respectively. Significant prognostic factors for healed were age (<12 years old) and root development stage (stages 4 and 5). Changes in the apical diameter, root length, root width, and radiographic root area after REPs were 56.8%, 8.3%, 23.2%, and 21.7%, respectively. Significant prognostic factors for continued root developmevnt were age and etiology of pulpal disease (from caries or dental anomalies). The sensibility test response rate was 41.7% with significant positive factors of ethylenediaminetetraacetic acid irrigation and capping material level above the cemento-enamel junction. REPs demonstrated high functional retention and healed rates. Patients <12 years old presented a higher healed rate and continued root development (excluding root length). Dental caries or anomalies had higher continued root development compared with dental trauma. The sensibility test response was related to ethylenediaminetetraacetic acid irrigation and level capping material. [ABSTRACT FROM AUTHOR]

Migration of dental pulp stromal cells (DPSCs) significantly responds to wound healing after pulp injury. Deriving from low compliance characteristics, pulp tissue regeneration is challenging and depends on the microenvironmental signals. Exosomes can maintain and carry bioactive proteins that are crucial in cell communication. Adipose tissue-derived stromal vascular fraction (AD-SVF), a heterogeneous group of progenitor cells, is a promising source of exosomes. Discover the impact of exosomes derived from an adipose-derived stromal-vascular fraction (AD-SVF Exo) on human dental pulp stromal cells (hDPSCs) migration. Methods: In-vitro design involving AD-SVF Exo applied to hDPSCs cultivated until 80% confluence and 3rd-4th passage. AD-SVF Exo isolation through size exclusion chromatography (SEC). The AD-SVF Exo was characterized using Nanoparticle Tracking Analysis (NTA) and flow cytometry assays. hDPSCs were exposed to AD-SVF Exo (0% as the control group, 0.1%, and 1% as the experimental group), subjected to a scratch wound assay, and observed at 6, 24, and 48 h. hDPSCs cultured expressed mesenchymal stem cell mesenchymal stem cell (MSC) markers and formed loose colonies with characteristic spindle-shaped morphology. AD-SVF Exo consisted of marker proteins CD9 and CD63, and NTA measurement demonstrated a diameter of 103 ± 24 nm in diameter with 1,6 x 108 particles/ml. Based on scratch assay, hDPSCs migration activity improved by reduced wound area in experimental groups. Data analyzed utilizing the Friedman (p < 0.001), and Kruskal Wallis (p < 0.05) test indicated differences in wound area after exposure of 0.1 % and 1 % AD-SVF Exo and observed at 6, 24, and 48 h. According to the findings of this research, AD-SVF Exo successfully enhances the wound healing capabilities of hDPSCs by improved migration activity, with the highest result found in 0.1% AD-SVF Exo. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to assess the histological and radiographic effects of sodium hexametaphosphate (SHMP) as a direct pulp capping (DPC) agent in immature permanent dog premolars. Methods A split-mouth design was employed with three healthy 4-month-old Mongrel dogs, each having 36 premolars. The premolars were randomly assigned to either SHMP or MTA. The specimens were stained with hematoxylin and eosin (H&E) and Masson’s trichrome, and histologically examined three months after the animals were sacrificed. To assess root maturity, radiographic changes in root length (RL), root surface area (RSA), and apical foramen width (AFW) were measured at baseline and after 3 months. Quantitative data were analyzed using the paired-sample t-test, while the qualitative data based on Stanley's histological scoring system were tested using the Monte Carlo exact test. The level of significance was set at 5%. Results Histological findings showed no significant differences between the two groups, except for the average thickness of the predentin and odontoblastic layers, which was significantly higher in the SHMP specimens (P 0.05), except for the change in RL, which was significantly longer in the SHMP group (P

Regenerative endodontic therapy (RET) of young permanent teeth with necrotic pulps and apical periodontitis in young people, deciduous tooth pulp may be utilized as a natural, biologic scaffold. Recent developments in stem cell biology and material sciences are beneficial for new treatment methods. Previously traumatized and necrotic young permanent tooth was treated with RET protocol. In the first visit, irrigation, and placement of triple antibiotic paste dressing were done. After that in the second visit, intracanal medication was removed and whole pulp tissue harvested from the deciduous tooth was transplanted in the young permanent tooth. Following placement of Biodentine® coronal barrier, access cavity was restored with acid-etch resin composite. This case report would highlight favorable outcome of RET using deciduous pulp autotransplantation in young permanent tooth using cone-beam computed tomography for 6 months’ follow-up.

Abstract Background Regenerative endodontic therapy (RET) is still coming up short to demonstrate histological evidence for true regeneration with clinically feasible protocol of cell homing in single visit approach. Aim The aim of the present study is to evaluate the regenerative potential of photobiomodulation (PBM) on RET in immature roots when photodynamic therapy (PDT) protocol is implemented for root canal disinfection in canine model. Materials and methods Seventy-two root canals were recruited, with sixty assigned to experimental groups and twelve to positive and negative controls. Following the induction of pulp necrosis and apical periodontitis, the roots were divided into two experimental groups: Group I received RET followed by PBM (seven sessions with an 808 nm diode laser at 300 mW for 90 s), and Group II received RET without PBM. Follow-ups were conducted at 1, 2, and 3 months (subgroups A, B, and C respectively). Qualitative and quantitative assessment was carried out histologically. All data were statistically analyzed with the Mann-Whitney U test and Bonferroni’s adjustment, as well as Chi square test. Results The newly formed hard tissue highly resembled true dentine where the dentinal tubules looked well organized lined by poly layers palisading pattern of rounded odontoblast-like cells with cytoplasmic processes extending through the predentine layer. GI exhibited statistically significantly higher scores of vital tissue infiltration and hard tissue deposition in subgroups A and B (P ≤ 0.05). The inflammatory cells scores were significantly lower in GI than in GII at all time intervals. However, no significance could be detected regarding apical closure. Conclusion The disinfection protocol of PDT and subsequent irradiation with low power laser in PBM protocol pose a promising potential for regenerative endodontics in immature teeth.

Objective: To develop a detergent-enzymatic method and evaluate the quality of a decellularized pulp scaffold for regenerative endodontics.Materials and methods: Biomaterial and mesenchymal stem cells (MSCs) were derived from dental pulp that was obtained following third molar extraction indicated for orthodontic reasons in patients aged 14-18 years. The detergent-enzymatic method enabled to obtain a decellularized scaffold from pulp samples. The proliferative activity and viability of dental pulp-derived MSCs were assessed using trypan blue staining and XTT assay. To assess tissue response, Wistar rats underwent subcutaneous implantation of native and decellularized dental pulp. Explanted samples were stained with hematoxylin-eosin on days 7 and 14.Results: The detergent-enzymatic treatment of the dental pulp demonstrated the absence of nuclear material, whereas the histoarchitecture of the dental pulp was disturbed. The DNA content in the sample of the decellularized scaffold was 22.79 ± 2.1 ng/mg of tissue; the amount of DNA in the native sample was 78.5 ± 5.4 ng/mg of tissue. According to XTT assay results, no cytotoxicity of the decellularized scaffold against MSCs was found. Biopsy specimens of the rats with implanted decellularized dental pulp were characterized by no signs of inflammation.Conclusions: The study results will enable to create a biomaterial that can be the base of a tissue-engineered structure of the dental pulp and be used for the regeneration of the pulp-dentin complex.

Background: Migration of dental pulp stromal cells (DPSCs) significantly responds to wound healing after pulp injury. Deriving from low compliance characteristics, pulp tissue regeneration is challenging and depends on the microenvironmental signals. Exosomes can maintain and carry bioactive proteins that are crucial in cell communication. Adipose tissue-derived stromal vascular fraction (AD-SVF), a heterogeneous group of progenitor cells, is a promising source of exosomes. Objective: Discover the impact of exosomes derived from an adipose-derived stromal-vascular fraction (AD-SVF Exo) on human dental pulp stromal cells (hDPSCs) migration. Methods: In-vitro design involving AD-SVF Exo applied to hDPSCs cultivated until 80% confluence and 3rd-4th passage. AD-SVF Exo isolation through size exclusion chromatography (SEC). The AD-SVF Exo was characterized using Nanoparticle Tracking Analysis (NTA) and flow cytometry assays. hDPSCs were exposed to AD-SVF Exo (0% as the control group, 0.1%, and 1% as the experimental group), subjected to a scratch wound assay, and observed at 6, 24, and 48 h. Results: hDPSCs cultured expressed mesenchymal stem cell mesenchymal stem cell (MSC) markers and formed loose colonies with characteristic spindle-shaped morphology. AD-SVF Exo consisted of marker proteins CD9 and CD63, and NTA measurement demonstrated a diameter of 103 ± 24 nm in diameter with 1,6 x 108 particles/ml. Based on scratch assay, hDPSCs migration activity improved by reduced wound area in experimental groups. Data analyzed utilizing the Friedman (p

Background/purpose: Sphingosine-1-phosphate (S1P) exhibits receptor-mediated physiological effects by facilitating the differentiation of mesenchymal stem cells toward the osteoblast lineage. This study aimed to determine the effect of S1P on odontogenic differentiation of mouse immortalized stem cells of dental apical papilla (iSCAP) and assess the distribution of the S1P receptor 1 (S1PR1) in the apical papilla and the root canal wall of immature rat molars. Materials and methods: Immunostaining for S1PR1 was conducted at the apex of the rat mandibular first molar and within the root canal wall. The iSCAP was treated with S1P and bone morphogenetic protein (BMP)-9 (for comparison), and the expression levels of the odontogenic differentiation marker were evaluated via real-time reverse-transcriptase quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Mineralization and lipid droplet formation were evaluated via Alizarin red and Oil red O staining. Results: S1PR1-positive cells were expressed in areas of both apical papilla and dentin-pulp interface of root canal wall. During the odontogenic differentiation of iSCAP, S1P and BMP-9 increased the expression of the differentiation marker mRNA and secreted proteins including dentin sialophosphoprotein, dentin matrix phosphoprotein 1, and matrix extracellular phosphoglycoprotein. The S1PR1 signaling pathway is involved in the action of S1P, but not that of BMP-9. S1PR1 signaling also facilitated mineralization in iSCAP and suppressed the differentiation of these cells into adipocytes. Conclusion: S1P induced odontogenic differentiation of iSCAP through S1PR1. Furthermore, S1PR1-positive cells were expressed in the apical papilla of immature rat molars and in the dentin-pulp interface where odontoblast-like cells exist.

Background/purpose: Platelet-rich fibrin (PRF) is a promising host-derived scaffold for regenerative endodontic treatment. This study investigated the effects of advanced PRF plus (A-PRF+) and injectable PRF (i-PRF) on the proliferation, migration, and differentiation of stem cells from apical papilla (SCAPs). Materials and methods: A-PRF+ and i-PRF were prepared using a DUO Quattro centrifuge following a standard protocol. A-PRF+ and i-PRF extract were diluted in Dulbecco's modified Eagle's medium and Ham's F-12 medium (DMEM/F12) to produce the experimental culture medium. DMEM/F12 and DMEM/F12 supplemented with 10% foetal bovine serum (FBS) were used as the negative control (NC) and positive control (PC) media, respectively. The proliferative ability of SCAPs was assessed using a counting method (haemocytometer). The migration ability was examined using a scratch-wound assay. Alkaline phosphatase, bone sialoprotein, dentin matrix protein 1, and dentin sialophosphoprotein expression were measured to determine the differentiation ability. Results: The proliferation, migration, and differentiation of SCAPs in the A-PRF+ group were similar to those of the PC group. In the i-PRF group, the cell number was significantly (p

The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment. However, novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative, biologically-driven regenerative medicine strategies. For example, cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration. These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators (HDACis, DNMTis, and ncRNAs), which are cost-effective and easily applied to stimulate pulp tissue regrowth. Unfortunately, many biological factors hinder the clinical development of regenerative therapies, including a lack of blood supply and poor infection control in the necrotic root canal system. Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability, cost concerns, and regulatory issues. This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration, explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition. It will highlight the components of dental pulp regenerative approaches, describe their current limitations, and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.

Abstract Background Regenerative endodontic procedures (REPs) offer the promise of restoring vitality and function to a previously necrotic and infected tooth. However, the nature of regenerated tissues following REPs remains unpredictable and uncontrollable. Decellularized extracellular matrix scaffolds have gained recent attention as scaffolds for regenerative endodontics. Objectives Preparation and characterization of a bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel for regenerative endodontic applications. Biocompatibility and regenerative capacity of the prepared scaffold were evaluated in vivo in a canine animal model. Methods Fifteen freshly extracted bovine molar teeth were used to prepare P-ECM hydrogels following approval of the institutional review board of the faculty of dentistry, Alexandria University. Decellularization and lyophilization of the extracted pulp tissues, DNA quantification and histological examination of decellularized P-ECM were done. P-ECM hydrogel was prepared by digestion of decellularized pulps. Prepared scaffolds were evaluated for protein content and release as well as release of VEGF, bFGF, TGF-β1 and BMP2 using ELISA. Rabbit dental pulp stem cells’ (rDPSCs) viability in response to P-ECM hydrogels was performed. Finally, proof-of-concept of the regenerative capacity of P-ECM scaffolds was assessed in an infected mature canine tooth model following REPs versus blood clot (BC), injectable platelet-rich fibrin (i-PRF) or hyaluronic acid (HA). Statistical analysis was done using independent t test, the Friedman test and chi-square tests (p value ≤ 0.05). Results DNA was found to be below the cut-off point (50 ng/mg tissue). Histological evaluation revealed absence of nuclei, retention of glycosaminoglycans (GAGs) and collagen content, respectively. P-ECM hydrogel had a total protein content of (493.12 µg/µl) and protein release was detected up to 14 days. P-ECM hydrogel also retained VEGF, bFGF, TGF-β1 and BMP2. P-ECM hydrogel maintained the viability of rDPSCs as compared to cells cultured under control conditions. P-ECM hydrogel triggered more organized tissues compared to BC, i-PRF and HA when used in REPs for necrotic mature teeth in dogs. Periapical inflammation was significantly less in HA and P-ECM groups compared to blood-derived scaffolds. Conclusion Bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel scaffold retained its bioactive properties and demonstrated a promising potential in regenerative endodontic procedures compared to conventional blood-derived scaffolds.

Abstract Background The use of biological scaffolds in regenerative endodontics has gained much attention in recent years. The search for a new biomimetic scaffold that contains tissue-specific cell homing factors could lead to more predictable tissue regeneration. The aim of this study was to prepare and characterize decellularized bovine dental pulp-derived extracellular matrix (P-ECM) hydrogels for regenerative endodontic applications. Methods Freshly extracted bovine molar teeth were collected. Bovine dental pulp tissues were harvested, and stored at -40º C. For decellularization, a 5-day protocol was implemented incorporating trypsin/EDTA, deionized water and DNase treatment. Decellularization was evaluated by DNA quantification and histological examination to assess collagen and glycosaminoglycans (GAGs) content. This was followed by the preparation of P-ECM hydrogel alone or combined with hyaluronic acid gel (P-ECM + HA). The fabricated scaffolds were then characterized using protein quantification, hydrogel topology and porosity, biodegradability, and growth factor content using Enzyme-linked immunosorbent assay (ELISA): transforming growth factor beta-1(TGF-β1), basic fibroblast growth factor (bFGF), bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Results Decellularization was histologically confirmed, and DNA content was below (50 ng/mg tissue). P-ECM hydrogel was prepared with a final ECM concentration of 3.00 mg/ml while P-ECM + HA hydrogel was prepared with a final ECM concentration of 1.5 mg/ml. Total protein content in P-ECM hydrogel was found to be (439.0 ± 123.4 µg/µl). P-ECM + HA showed sustained protein release while the P-ECM group showed gradual decreasing release. Degradation was higher in P-ECM + HA which had a significantly larger fiber diameter, while P-ECM had a larger pore area percentage. ELISA confirmed the retention and release of growth factors where P-ECM hydrogel had higher BMP-2 release, while P-ECM + HA had higher release of TGF-β1, bFGF, and VEGF. Conclusions Both P-ECM and P-ECM + HA retained their bioactive properties demonstrating a potential role as functionalized scaffolds for regenerative endodontic procedures.

Background Research has been conducted to assess the regenerative potential of dental pulp stem cells (DPSCs) following pretreatment of stem cells with certain molecules, bioactive compounds, plant extract and physical stimulation. Andrographis paniculata (AP) herbal extract with important medicinal properties is proven to have a preosteogenic effect on osteoblasts. Aim This study aimed to determine the effect of various concentrations of AP extract on the cytotoxicity and osteogenic and odontogenic potential of DPSCs. Methods and Material Dental pulp stem cells were subjected to treatment with various concentrations of AP herbal extract (7 ug/ml, 5.2 ug/ml, 3.5 ug/ml, 1.7 ug/ml and 0.8 ug/ml), following which the cells were subjected to tests-3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) analysis for cytotoxicity and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for expression of genes (bone morphogenetic protein (BMP), osteocalcin (OCN), dentin sialophosphoprotein (DSPP) and alkaline phosphatase (ALP)). Results AP extract at concentration of 0.8 ug/ml–5.2 ug/ml had no cytotoxicity supporting cell growth. 3.5 ug/ml showed significant upregulation of genes on the third day. Conclusion AP, a commonly occurring medicinal plant through its effect on DPSCs, could serve as an effective pretreatment modality for cell-based regenerative therapy and vital pulp therapy.

ABSTRACT Background/Aim Materials and Methods Results Conclusions Regenerative endodontic treatment is a promising approach for healing periapical lesions and continuous root maturation. Although previous studies have reported its outcomes, the dynamics of morphological changes over time remain unclear. Therefore, this study aimed to evaluate changes in the periapical status and root dimensions over a 60‐month follow‐up period.The follow‐up duration, periapical status changes, calcific barrier formation, degree of apical closure and radiographic root area changes were compared with those of the last follow‐up in this retrospective study. Radiographic root area changes were calculated as the difference between the total root and total canal areas.Fifty‐eight patients (81 teeth) underwent regenerative endodontic treatment during the study period, of whom 32 patients (36 teeth, 62%) were included. The survival and success rates of the treated teeth were 100% and 94.4%, respectively. All teeth developed a calcific bridge in the cervical third of the root canal, indicating the presence of vital tissue. Apical narrowing (partial or total) was observed in 75% of the cases. The root maturation stage affected the percentage increase in the radiographic root area. Teeth in Cvek stages II–III showed a higher radiographic root area increase than more mature teeth. All tooth radiographic root areas increased significantly in the initial 20 months of the treatment and moderately thereafter.Regenerative endodontic treatment is a safe approach for traumatised immature teeth. The presence of a radiographic calcified bridge may be an early indication of treatment success. The main complete tooth morphological changes occur after approximately 20 months posttreatment. These findings may help clinicians better understand the time‐dependent changes in the root morphology after treatment, improve the follow‐up schedule and predict the progress of healing during follow‐up visits. [ABSTRACT FROM AUTHOR]

Background: The use of biological scaffolds in regenerative endodontics has gained much attention in recent years. The search for a new biomimetic scaffold that contains tissue-specific cell homing factors could lead to more predictable tissue regeneration. The aim of this study was to prepare and characterize decellularized bovine dental pulp-derived extracellular matrix (P-ECM) hydrogels for regenerative endodontic applications. Methods: Freshly extracted bovine molar teeth were collected. Bovine dental pulp tissues were harvested, and stored at -40º C. For decellularization, a 5-day protocol was implemented incorporating trypsin/EDTA, deionized water and DNase treatment. Decellularization was evaluated by DNA quantification and histological examination to assess collagen and glycosaminoglycans (GAGs) content. This was followed by the preparation of P-ECM hydrogel alone or combined with hyaluronic acid gel (P-ECM + HA). The fabricated scaffolds were then characterized using protein quantification, hydrogel topology and porosity, biodegradability, and growth factor content using Enzyme-linked immunosorbent assay (ELISA): transforming growth factor beta-1(TGF-β1), basic fibroblast growth factor (bFGF), bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Results: Decellularization was histologically confirmed, and DNA content was below (50 ng/mg tissue). P-ECM hydrogel was prepared with a final ECM concentration of 3.00 mg/ml while P-ECM + HA hydrogel was prepared with a final ECM concentration of 1.5 mg/ml. Total protein content in P-ECM hydrogel was found to be (439.0 ± 123.4 µg/µl). P-ECM + HA showed sustained protein release while the P-ECM group showed gradual decreasing release. Degradation was higher in P-ECM + HA which had a significantly larger fiber diameter, while P-ECM had a larger pore area percentage. ELISA confirmed the retention and release of growth factors where P-ECM hydrogel had higher BMP-2 release, while P-ECM + HA had higher release of TGF-β1, bFGF, and VEGF. Conclusions: Both P-ECM and P-ECM + HA retained their bioactive properties demonstrating a potential role as functionalized scaffolds for regenerative endodontic procedures. [ABSTRACT FROM AUTHOR]

Background: Regenerative endodontic procedures (REPs) offer the promise of restoring vitality and function to a previously necrotic and infected tooth. However, the nature of regenerated tissues following REPs remains unpredictable and uncontrollable. Decellularized extracellular matrix scaffolds have gained recent attention as scaffolds for regenerative endodontics. Objectives: Preparation and characterization of a bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel for regenerative endodontic applications. Biocompatibility and regenerative capacity of the prepared scaffold were evaluated in vivo in a canine animal model. Methods: Fifteen freshly extracted bovine molar teeth were used to prepare P-ECM hydrogels following approval of the institutional review board of the faculty of dentistry, Alexandria University. Decellularization and lyophilization of the extracted pulp tissues, DNA quantification and histological examination of decellularized P-ECM were done. P-ECM hydrogel was prepared by digestion of decellularized pulps. Prepared scaffolds were evaluated for protein content and release as well as release of VEGF, bFGF, TGF-β1 and BMP2 using ELISA. Rabbit dental pulp stem cells' (rDPSCs) viability in response to P-ECM hydrogels was performed. Finally, proof-of-concept of the regenerative capacity of P-ECM scaffolds was assessed in an infected mature canine tooth model following REPs versus blood clot (BC), injectable platelet-rich fibrin (i-PRF) or hyaluronic acid (HA). Statistical analysis was done using independent t test, the Friedman test and chi-square tests (p value ≤ 0.05). Results: DNA was found to be below the cut-off point (50 ng/mg tissue). Histological evaluation revealed absence of nuclei, retention of glycosaminoglycans (GAGs) and collagen content, respectively. P-ECM hydrogel had a total protein content of (493.12 µg/µl) and protein release was detected up to 14 days. P-ECM hydrogel also retained VEGF, bFGF, TGF-β1 and BMP2. P-ECM hydrogel maintained the viability of rDPSCs as compared to cells cultured under control conditions. P-ECM hydrogel triggered more organized tissues compared to BC, i-PRF and HA when used in REPs for necrotic mature teeth in dogs. Periapical inflammation was significantly less in HA and P-ECM groups compared to blood-derived scaffolds. Conclusion: Bovine dental pulp-derived extracellular matrix (P-ECM) hydrogel scaffold retained its bioactive properties and demonstrated a promising potential in regenerative endodontic procedures compared to conventional blood-derived scaffolds. [ABSTRACT FROM AUTHOR]

Background: Bibliometric analysis is a critical indicator of the influence and relevance of scientific papers, whilst also highlighting key contributors and gaps in knowledge in a scientific field. Objectives: To update and analyse the 100 most‐cited papers in regenerative endodontics from 2019 to 2023. Methods: A search of the most‐cited recent papers focusing on regenerative endodontics using journals included in the category, 'Dentistry, Oral Surgery & Medicine', in the Clarivate Web of Science database from 2019 to 2023 was performed. Three researchers conducted the study selection and data extraction. Data extraction included publication title and year, authors, number and mean number of citations, institution, country and continent, study design, journal title, keywords and research topic. Citation counts were also collected in Google Scholar and Scopus databases. Graphical bibliometric networks were created using VOSviewer software. Results: The number of citations of the 100 most‐cited articles ranged from 6 to 85. Most were published in 2020 (n = 48), principally in the Journal of Endodontics (47%), followed by International Endodontic Journal (13%), Journal of Dental Research (6%) and Dental Materials (6%). Laboratory study was the most common study design amongst the included papers (n = 47), followed by narrative reviews (n = 17) and observational studies (n = 16). The most frequent first author on the top three most‐cited papers was Hacer Aksel, whilst Adham A. Azim (n = 6; 89 citations) contributed most to the top 100 articles. The institution from which most articles originated was the University of Hong Kong (China) (n = 5; 81 citations), whereas the corresponding authors were predominantly from the United States of America (USA) (n = 31; 560 citations). The VOSviewer map of co‐authorship demonstrated research collaborative clusters. 'Regenerative endodontics' and 'stem‐cells' were the most employed keywords (37 and 36 occurrences respectively). Discussion: The current study was designed not only to showcase the most influential papers in regenerative endodontics since 2019 but also to provide a better understanding of global research in this area over the last five years. Conclusions: This bibliometric analysis highlighted papers, authors, institutions and keywords in regenerative endodontics. The 100 most‐cited papers primarily consisted of laboratory studies published in the USA, focusing on evaluating biomaterials and scaffold design strategies in contact with stem cells. Clinical studies and systematic reviews representing higher levels of scientific evidence are currently not the most influential in the regenerative endodontic field. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is a promising host-derived scaffold for regenerative endodontic treatment. This study investigated the effects of advanced PRF plus (A-PRF+) and injectable PRF (i-PRF) on the proliferation, migration, and differentiation of stem cells from apical papilla (SCAPs). A-PRF+ and i-PRF were prepared using a DUO Quattro centrifuge following a standard protocol. A-PRF+ and i-PRF extract were diluted in Dulbecco's modified Eagle's medium and Ham's F-12 medium (DMEM/F12) to produce the experimental culture medium. DMEM/F12 and DMEM/F12 supplemented with 10% foetal bovine serum (FBS) were used as the negative control (NC) and positive control (PC) media, respectively. The proliferative ability of SCAPs was assessed using a counting method (haemocytometer). The migration ability was examined using a scratch-wound assay. Alkaline phosphatase , bone sialoprotein , dentin matrix protein 1 , and dentin sialophosphoprotein expression were measured to determine the differentiation ability. The proliferation, migration, and differentiation of SCAPs in the A-PRF+ group were similar to those of the PC group. In the i-PRF group, the cell number was significantly (p < 0.01) lower than that of the A-PRF+ group on days 8 and 10; the percentage of the scratched area on days 1 and 2 was significantly higher than in the A-PRF+ group (p < 0.05). The mRNA expression levels of biomarkers in the i-PRF group were similar to those in the A-PRF+ group. Both A-PRF+ and i-PRF induce SCAPs proliferation, migration, and differentiation. However, A-PRF+ was superior in supporting the proliferation and migration of SCAPs. [ABSTRACT FROM AUTHOR]

Sphingosine-1-phosphate (S1P) exhibits receptor-mediated physiological effects by facilitating the differentiation of mesenchymal stem cells toward the osteoblast lineage. This study aimed to determine the effect of S1P on odontogenic differentiation of mouse immortalized stem cells of dental apical papilla (iSCAP) and assess the distribution of the S1P receptor 1 (S1PR1) in the apical papilla and the root canal wall of immature rat molars. Immunostaining for S1PR1 was conducted at the apex of the rat mandibular first molar and within the root canal wall. The iSCAP was treated with S1P and bone morphogenetic protein (BMP)-9 (for comparison), and the expression levels of the odontogenic differentiation marker were evaluated via real-time reverse-transcriptase quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Mineralization and lipid droplet formation were evaluated via Alizarin red and Oil red O staining. S1PR1-positive cells were expressed in areas of both apical papilla and dentin-pulp interface of root canal wall. During the odontogenic differentiation of iSCAP, S1P and BMP-9 increased the expression of the differentiation marker mRNA and secreted proteins including dentin sialophosphoprotein, dentin matrix phosphoprotein 1, and matrix extracellular phosphoglycoprotein. The S1PR1 signaling pathway is involved in the action of S1P, but not that of BMP-9. S1PR1 signaling also facilitated mineralization in iSCAP and suppressed the differentiation of these cells into adipocytes. S1P induced odontogenic differentiation of iSCAP through S1PR1. Furthermore, S1PR1-positive cells were expressed in the apical papilla of immature rat molars and in the dentin-pulp interface where odontoblast-like cells exist. [ABSTRACT FROM AUTHOR]

Dens invaginatus is a developmental dental anomaly that can predispose the tooth to pulp and periradicular disease. Management of this condition can be challenging because of anatomic and microbiologic issues. This case report describes the regenerative endodontic treatment using a strategic antimicrobial protocol for management of an immature maxillary lateral incisor with type-II dens invaginatus associated with apical periodontitis in a 13-year-old patient. The tooth presented with a complex anatomy and was associated with an active sinus tract. Because the true root canal was not negotiable in its coronal part due to the presence of the dens invaginatus, the closed end of the invagination (pseudocanal) was perforated to permit access to the apical segment of the true root canal for cleaning and disinfection. Both the invagination and the true canal were treated using an antimicrobial regimen based on chemomechanical preparation with sodium hypochlorite irrigation, supplementary disinfection with passive ultrasonic irrigation and interappointment calcium hydroxide medication. After 2 exchanges of calcium hydroxide medication, the sinus tract did not disappear, then the antimicrobial protocol was changed to include an antibiotic solution for irrigation and antibiotic paste for intracanal medication. After signs and symptoms disappeared, regenerative endodontic treatment was performed by inducing blood clot formation within the root canal. The coronal canal segment including the invagination was filled with Biodentine. Follow-up including cone-beam computed tomography examination showed complete healing of the apical periodontitis lesion and mineralized tissue formation at the apical portion of the true root canal. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the hypothesis that a combination of D-amino acids (DAAs) and trans -cinnamaldehyde (TC) demonstrates superior antibiofilm activity to calcium hydroxide (CH) and untreated controls. In this 3-part in vitro study, the concentration of DAAs (D-methionine, D-leucine, D-tyrosine, and D-tryptophan) that would significantly decrease Enterococcus faecalis and Actinomyces naeslundii biofilm biomass was first determined. Then, the effect of TC + selected DAAs on polymicrobial biofilms was characterized by quantifying the biomass and biofilm viability. Finally, the antibiofilm effects of TC + DAA was compared with CH and untreated controls by (i) determining bacterial viability and (ii) quantifying biofilm matrix composition using selective fluorescence-binding analysis. Statistical analysis was performed using one-way ANOVA and appropriate multiple comparisons test, with P <.05 considered as statistically significant. TC (0.06%) + D-tyrosine (1 mM) + D-tryptophan (25 mM) significantly reduced the biomass and biofilm viability compared to the control (P <.05). While no significant difference was observed between TC + DAA and CH in the cultivable bacterial counts (P >.05), confocal microscopy demonstrated a significantly greater percentage of dead bacteria in TC + DAA-treated biofilms compared to CH and the control (P <.05). TC + DAA significantly decreased the biovolume and all the examined components of the biofilm matrix quantity compared to the control, while CH significantly reduced only the exopolysaccharide quantity (P <.05). The combination of TC + D-tyrosine + D-tryptophan demonstrated superior antibiofilm activity (biofilm bacterial killing and reduction of matrix quantity) to CH and has potential to be developed as an intracanal medicament. [ABSTRACT FROM AUTHOR]

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Introduction: This review evaluates the effectiveness of treatment modalities for immature teeth with pulp necrosis, focusing on calcium hydroxide (CH) and mineral trioxide aggregate (MTA) apexification, as well as regenerative endodontic treatments (RETs). Recent advancements and clinical outcomes are highlighted. Materials and Methods: A comprehensive search of MEDLINE (PubMed), Embase, Cochrane Library, Scopus, and grey literature was conducted from inception to July 2024. Systematic reviews and meta-analyses (SR/MAs) assessing apexification and RET outcomes in immature teeth with pulp necrosis were included. Studies were selected based on predefined criteria, and data on study design, interventions, and outcomes were extracted. Methodological quality was evaluated using the AMSTAR-2 tool. Results: 31 SR/MAs were included. The quality ranged from critically low to low, except one rated as high. MTA apexification was more effective than CH for faster apical barrier formation, though overall success rates were similar. MTA is preferred for its efficiency, but standardized protocols are needed, and tooth discoloration was noted as a potential complication. RET generally outperforms apexification in root maturation, with platelet concentrates like platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) showing promising results; PRP was associated with greater root length, while PRF showed superior apical healing. Variability in RET outcomes was noted due to the lack of standardized protocols. Comparative studies of RET versus apexification showed no significant differences in survival or overall success rates. RET often provides better apical closure and root development, though results vary. Both approaches are viable, but more research with standardized protocols and larger samples is needed to establish definitive clinical advantages. Conclusions: MTA apexification and RET are viable alternatives to CH apexification, with RET showing greater potential for root development and apical healing. Future research should focus on developing standardized protocols and uniform RET guidelines, and evaluating long-term outcomes to establish efficacy and safety. [ABSTRACT FROM AUTHOR]

Regenerative endodontic therapy (RET) of young permanent teeth with necrotic pulps and apical periodontitis in young people, deciduous tooth pulp may be utilized as a natural, biologic scaffold. Recent developments in stem cell biology and material sciences are beneficial for new treatment methods. Previously traumatized and necrotic young permanent tooth was treated with RET protocol. In the first visit, irrigation, and placement of triple antibiotic paste dressing were done. After that in the second visit, intracanal medication was removed and whole pulp tissue harvested from the deciduous tooth was transplanted in the young permanent tooth. Following placement of Biodentine® coronal barrier, access cavity was restored with acid-etch resin composite. This case report would highlight favorable outcome of RET using deciduous pulp autotransplantation in young permanent tooth using cone-beam computed tomography for 6 months' follow-up. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the distribution pattern of tenascin‐C and syndecan‐1 in the dental mesenchyme during root development of immature swine teeth in order to define the differentiation dynamics of both pulp tissue progenitors and apical papilla cells, as well as to assess the adequacy criticize of the apical papilla to induce dentin–pulp regeneration. Methods: Three 7‐month‐old miniature swine were used in this study. A total of 12 teeth, including two immature permanent incisors and two premolar teeth of each case, were extracted and processed for histological and immunohistochemical analysis. Different populations of mesenchymal cells located at the root apex were morphologically evaluated in hematoxylin–eosin serial sections. Additionally, the distribution patterns of tenascin‐C and syndecan‐1 were assessed immunohistochemically. Results: Syndecan‐1 was strongly expressed in the dental pulp, particularly along the odontoblasts of the root and the newly deposited predentin layer. Tenascin‐C was intensely expressed in the dental pulp. The apical papilla and dental follicle showed no expression of either molecule. Conclusions: Cell differentiation potential in the developing swine apex is progressively restricted to the newly formed dental pulp, whereas phenotypic expression of apical papilla cells remains undetermined unless the new microenvironment triggers cell differentiation towards the odontoblastic lineage. [ABSTRACT FROM AUTHOR]

Introduction: Diseases involving the periapex are infectious pathologies caused by microorganisms that colonize the coronal and radicular dental pulp. In this context, incomplete rhizogenesis presents a major clinical challenge for dentists. Objective: To verify the clinical applicability of the pulp revascularization technique in necrotic teeth with incomplete rhizogenesis. Methodology: This is an integrative literature review. The bibliographic search was carried out in the Virtual Health Library (BVS) and National Library of Medicine (Pubmed), accounting for 10 studies. The search was guided by the selection of words from the Health Sciences Descriptors (DeCS/MeSH). The eligibility criteria used were prognostic studies, systematic reviews, and clinical cases, published between 2018-2023, in English and Portuguese, available free of charge and that answered the research question. Results: The most prevalent language was English n = 10 (100%), the main indexing platform was Pubmed, with 7 articles (70%), with a preference for the Journal of Endodontics with 2 studies (20%), published in 2021, with 4 studies (40%). The main type of study was the systematic review, with 7 articles (70%). Conclusion: Revascularization demonstrates to have a viable clinical applicability for cases of pulp necrosis in teeth with incomplete rhizogenesis. [ABSTRACT FROM AUTHOR]

Objectives: To synthesize casein enzymatic hydrolysate (CEH)-laden gelatin methacryloyl (GelMA) fibrous scaffolds and evaluate the cytocompatibility and anti-inflammatory effects on dental pulp stem cells (DPSCs). Materials and methods: GelMA fibrous scaffolds with 10%, 20%, and 30% CEH (w/w) and without CEH (control) were obtained via electrospinning. Chemo-morphological, degradation, and mechanical analyses were conducted to evaluate the morphology and composition of the fibers, mass loss, and mechanical properties, respectively. Adhesion/spreading and viability of DPSCs seeded on the scaffolds were also assessed. The anti-inflammatory potential on DPSCs was tested after the chronic challenge of cells with lipopolysaccharides (LPS), followed by treatment with extracts obtained after immersing the scaffolds in α-MEM. The synthesis of the pro-inflammatory cytokines IL-6, IL-1α, and TNF-α was measured by ELISA. Data were analyzed by ANOVA/post-hoc tests (α = 5%). Results: CEH-laden electrospun fibers had a larger diameter than pure GelMA (p ≤ 0.036). GelMA scaffolds laden with 20% and 30% CEH had a greater mass loss. Tensile strength was reduced for the 10% CEH fibers (p = 0.0052), whereas no difference was observed for the 20% and 30% fibers (p ≥ 0.6736) compared to the control. Young’s modulus decreased with CEH (p < 0.0001). Elongation at break increased for the 20% and 30% CEH scaffolds (p ≤ 0.0038). Over time, DPSCs viability increased across all groups, indicating cytocompatibility, with CEH-laden scaffolds exhibiting greater cell viability after seven days (p ≤ 0.0166). Also, 10% CEH-GelMA scaffolds decreased the IL-6, IL-1α, and TNF-α synthesis (p ≤ 0.035). Conclusion: CEH-laden GelMA scaffolds facilitated both adhesion and proliferation of DPSCs, and 10% CEH provided anti-inflammatory potential after chronic LPS challenge. Clinical relevance: CEH incorporated in GelMA fibrous scaffolds demonstrated the potential to be used as a cytocompatible and anti-inflammatory biomaterial for vital pulp therapy. [ABSTRACT FROM AUTHOR]

The success of regenerative endodontic procedures (REPs) is significantly influenced by the choice of endodontic irrigant solution. However, the impact of these solutions on the viability of stem cells from the apical papilla (SCAP), a critical component of the REP, remains a subject of ongoing debate. This study aimed to investigate the effects of various endodontic irrigant solutions on the viability of stem cells from the apical papilla in an in vitro setting. A systematic literature search was conducted using databases such as PubMed/Medline, Scopus, the Cochrane Library, Web of Science, Embase, gray literature, and reference lists up to August 2023. The search was limited to in vitro studies investigating the impact of endodontic irrigant solutions on SCAP viability. The risk of bias in these studies was evaluated using the Joanna Briggs Institute's checklist. Of the 131 articles retrieved, 14 were selected for review. The effects of eighteen different root canal irrigants, such as ethylenediaminetetraacetic acid, sodium hypochlorite, chlorhexidine, and citric acid, on the viability of SCAPs were evaluated. The risk-of-bias analysis showed a high risk in sample randomization and size justification but a low risk in other areas. The effects of endodontic irrigant solutions on the viability of SCAPs are concentration dependent. Concentrations higher than 1.5% sodium hypochlorite, 2 % chlorhexidine, 10 % citric acid, and 2.5 % EDTA significantly reduced cell viability. However, additional research is necessary to determine the effect of these irrigants on tissue regeneration. [ABSTRACT FROM AUTHOR]

In regenerative endodontics, eradicating antibiotic residues from root canals is imperative, given their detrimental effects on human apical papilla stem cells. Previous antibiotic removal studies lacked precision in identifying types and quantities of residual antibiotics. High-performance liquid chromatography (HPLC) enhances sensitivity and specificity, enabling accurate detection and quantification of residual drugs. Using HPLC analysis, this study explored the influence of vehicles and irrigation solutions and methods on double antibiotic paste (DAP) removal from root canals. Two DAP formulations, each containing 5 mg/mL ciprofloxacin and metronidazole, were created using distinct vehicles: macrogol and propylene glycol (MP) or hydroxypropyl methylcellulose (HPMC). Subsequently, 5 μL of DAP was applied to 200 simulated immature teeth with open apices (n = 100 per formulation) and cultured for 28 days at 37°C. Samples were then divided into 11 groups (n = 20 per group), and canals were irrigated with 17% ethylenediaminetetraacetic acid or 10% citric acid, employing a positive pressure syringe or passive ultrasonic irrigation. The irrigation solution and dentin sample from each tooth were evaluated via HPLC for ciprofloxacin and metronidazole quantification. Citric acid exhibited significantly superior efficacy in antibiotic removal from root canals, with no observable effect of irrigation methods on drug removal. The HPMC-based DAP formulation significantly enhanced ciprofloxacin removal compared with MP-based DAP. For antibiotic paste removal from root canals, citric acid is effective, and HPMC is a preferable vehicle over MP. Overall, HPLC is a valuable method for detecting, removing, and quantifying residual antibiotics in root canals. [ABSTRACT FROM AUTHOR]

This study aimed to investigate access to care and financial considerations associated with the endodontic treatment of immature permanent teeth. Surveys were distributed to endodontists (n = 2,457) and pediatric dentists (n = 3,974) in the United States. Data were analyzed using X2 analysis and logistic regression. The level of significance was set to 0.05. The response rate was 13% (n = 840). Respondent specialist groups were similar by age and years since specialty residency completion, but significantly different with regard to primary practice setting (eg private practice, Federally Qualified Health Center, hospital), (P =.001). The majority (91%) of respondents reported participation with dental insurance. Pediatric dentists (69%) were significantly more likely than endodontists (17%) to participate with public-payer dental insurance (P <.001). The majority of respondents (82%) indicated that patients reported economic factors (time or money) as a barrier to accessing endodontic treatment. Pediatric dentists were significantly more likely to consider economic factors when planning for treatment (P <.001). Pediatric dentists were more likely than endodontists to have the opinion that endodontic procedures for treatment of necrotic immature permanent teeth should cost less than root canal therapy (apexification, P <.001; regenerative endodontic procedures, P =.002). Pediatric dentists (33%) reported encountering barriers when attempting to refer their patients to an endodontist. Inability to find an endodontist that participates with dental insurance was the most frequently cited barrier. Limited clinician participation with dental insurance and gaps in insurance coverage for endodontic procedures appear to contribute to access to care barriers for pediatric patients. [ABSTRACT FROM AUTHOR]

Advanced research in biomedical engineering, together with rising treatment standards and the demand for non-conventional methods, have contributed to the explosive growth of the field of dentistry known as regenerative dentistry. Stem cells, scaffolds, and bioactive substances are the three main elements of tissue engineering, the field that forms the basis of regenerative dentistry. Because of these remarkable properties, stem cells produced from dental tissue are very relevant in this field. In a wide spectrum of dental specializations, regenerative techniques have brought novel options to many established treatment protocols. Consider the alternative to conventional root canal therapy provided by pulp revascularization and other regenerative endodontic procedures. Thanks to 3-D bioprinting and computer-aided design, which have revolutionized oral and maxillofacial tissue engineering, modified guided tissue regeneration procedures are gradually replacing standard surgical and nonsurgical periodontal therapy. This paper provides an overview of the most current therapeutic approaches that have been used in clinical settings and highlights the importance of dental tissue-derived stem cells for regenerative dentistry.

Background Propolis is a natural substance produced by honeybees that has various biological properties including, anti-inflammatory, antioxidant and antimicrobial properties. Although previous studies have evaluated the antimicrobial effects of propolis in dentistry, its effects on dental pulp stem cell (DPSC) viability, migration, and differentiation are yet not well understood. The objective of this study was to investigate the effects of Chinese propolis on viability/proliferation, migration, differentiation and cytokine expression in DPSCs. Methods Commercially available DPSCs (Lonza) were treated with aqueous extract of propolis (AEP) or ethanolic extract of propolis (EEP), and viability/proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays and quantification of nuclear staining. DPSC differentiation into mineralizing cells was evaluated with Alizarin red staining and cell migration was assessed using Boyden Chamber Transwell inserts. Cytokine expression was measured by RT-qPCR. AEP and EEP at 0.03 and 0.1 mg/mL did not affect DPSC viability/proliferation for up to 7-days treatment. Results Higher doses (0.33–33 mg/mL) induced a dose dependent decrease in DPSC viability/proliferation with a more prominent effect with EEP at 7 days. Neither AEP nor EEP induced DPSC differentiation into mineralizing cells, but both AEP and EEP (0.03–0.1 mg/ml) induced a dose dependent increase in DPSC migration. In addition, EEP prevents the upregulation of IL1b and IL6 but not IL8 and CCL2 in response to lipopolysaccharide stimulation. AEP has less potent anti-inflammatory effects and prevents only IL1b upregulation. Conclusion This study provides new information about the biologic properties of ethanolic and aqueous extracts of propolis and shows that propolis, at doses that do not affect cell viability, induces DPSC migration and has anti-inflammatory properties. These data highlight the potential use of propolis as an alternative intra-canal medicament for regenerative endodontic procedures.

ABSTRACT Objectives This study aims to compare the application of three types of normal scaffolds—native chitosan, enzymatically modified chitosan, and blood clot (BC)—on pulp regeneration in the teeth of experimental dogs through histological examination, to determine the quantity and type of new tissues formed within the root canal. Materials and Methods The research sample consisted of 32 root canals from 20 premolars of two male local experimental dogs. The sample was randomly divided into a control group, in which no intervention was performed on the teeth, and three experimental groups based on the type of scaffold used: the BC group, the native chitosan combined with BC (NCS + BC) group, and the enzymatically modified chitosan combined with BC (EMCS + BC) group. Mechanical and chemical cleaning of the canals was performed, followed by the application of the studied scaffolds within the root canals. After 3 months, the teeth were extracted and prepared for histological study, where two variables were studied: the percentage of total vital tissue (soft and hard; VT%) and the percentage of soft vital tissue only (ST%). A one‐way ANOVA and Bonferroni tests were used to determine significant differences between the groups at a 95% confidence level. Results The VT% values were significantly higher in the EMCS + BC group compared to both the NCS + BC and BC groups. The ST% values were also significantly higher in the EMCS + BC group compared to the BC group. However, no significant differences in ST% values were observed between the NCS + BC group and either the BC or EMCS + BC groups. Conclusions Within the limitations of this study, we conclude that the application of enzymatically modified chitosan scaffolds combined with BC yields superior results in pulp regeneration, which contributes to the formation of pulp‐like tissue and cells resembling odontoblasts, as well as apex closure with tissue resembling bone tissue.

Objective: To assess the clinical outcomes of regenerative endodontic procedures using autologous platelet concentrate. Both regeneration and apexification procedures were examined and compared with each other. Material and Methods: The PRISMA 2020 Checklist has been utilized to carry out the systematic review and meta-analysis for the present study. PubMed, Scopus, Web of Science, EBSCO, Embase, and ISI Web of Knowledge have been reviewed for systematic literature until May 2023. A fixed-effect model and a Mantel-Haenszel methodology have been used to measure the risk ratio's 95% confidence interval. Then, Meta-analyses were carried out utilizing Stata/MP version 17. Results: Duplicate studies were eliminated from the first review, 849 studies' abstracts were reviewed, two authors reviewed 103 papers' full texts, and finally, 20 articles were selected. The survival rate in regenerative endodontic procedures between apexification and regenerative endodontic procedures was -0.01 (RR: -0.01, 95% CI: -0.05, 0.02; p=0.35). Conclusion: Throughout the present meta-analysis, regenerative endodontic therapy is an effective intervention with a high survival and success rate in managing immature necrotic permanent teeth.

Endodontics is evolving with modern innovations for conservatively managing the various dental problems involving pulpal or periradicular tissue of primary and permanent teeth. Lasers have been reported with favorable clinical evidence, particularly in tackling the endodontic problems effectively. Recently, the application of lasers in the form of photobiomodulation therapy or low-level laser therapy has been reported in many recent scientific studies/researches with successful results. Hence, this narrative review critically appraise the existing scientific literature and highlights the photobiomodulation technique of lasers as noninvasive therapeutic modality in different pediatric endodontic therapies or procedures (direct pulp capping, pulpotomy, noninvasive treatment of periapical lesion, regenerative endodontics, postendodontic pain management, etc.).

Pulp necrosis is diagnosed when the pulp is presented asymptomatic in response to pulp tests. Its conventional management in immature permanent teeth is by apexification. However, this treatment has the disadvantage of weakening the root walls tending to root fracture and pulp does not present revitalization. Due to that, the use of regenerative endodontic treatment has been recommended and it aims to regenerate the dentin-pulp complex, in addition to root growth, maturation and apical closure through cell replacement within the root tissue using stem cells and growth factors. Cloth formation is used as a scaffold for stem cells from the apical papilla to stimulate tissue regeneration. The aim of this review is to synthesize the available information about this treatment and to contribute to the possibility of the creation of a protocol consensus of this treatment.

Introduction: Immature teeth are more susceptible to fracture, and intracanal medicaments and coronal filling materials used in regenerative endodontics affect their optic and mechanical properties. This study aimed to evaluate the fracture resistance and coronal discoloration of simulated immature teeth following the placement of several intracanal medicaments and coronal sealing materials. Materials and Methods: Eighty-eight premolars simulating immature teeth were divided into 11 groups (n = 8 each) according to the type of intracanal medicament (triple antibiotic paste [TAP]; double antibiotic pastes [DAP]; calcium hydroxide [Ca(OH)2]) and used coronal barrier materials (mineral trioxide aggregate [MTA] and calcium-enriched mixture [CEM]). A bonding agent was applied in half of the samples in the groups where antibiotic pastes were used (n = 8). After incubating for 3 weeks, the sample’s fracture resistance and color change were evaluated. Data analysis was conducted using multivariate and one-way analysis of variance, Tukey’s honestly significant difference post hoc, and the Kruskal–Wallis tests (α =0.05). Results: The color change after placing the medicaments was comparable among the groups. However, after 3 months, the color change in the TAP-CEM-No-Bonding group was higher than the control, Ca(OH)2-MTA, and DAP-MTA-No-Bonding groups (P < 0.05). The fracture resistance of the TAP-MTA-Bonding, DAP-CEM-Bonding, Ca(OH)2-MTA, and Ca(OH)2-CEM was lower than the control group (P < 0.05). Conclusion: Simultaneous use of DAP-MTA without a dentin bonding agent led to comparable color change and fracture resistance to the control group.

This study aimed to assess better effectiveness between regenerative endodontic procedures (REP) and apexification procedures (AP) with mineral trioxide aggregate (MTA) and calcium hydroxide for inducing root end apex closure. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed and registered in PROSPERO-CRD42023398997. Electronic databases were searched for studies evaluating effectiveness of REP and AP in terms of survival rate, success rate, increase in root length, root width and decrease in apical diameter. Cochrane risk of bias (RoB) -2 tool was used for quality assesssment using RevMan 5.3. The risk ratio (RR) and standardized mean difference (SMD) was used as summary statistic measure with random effect model (P < 0.05). Nine studies were included in qualitative synthesis and eight studies for meta-analysis. Quality assessment revealed moderate to low risk of bias. The pooled estimate through RR and SMD favoured REP being superior to AP for better survival rate (RR = 1.01 (0.96 – 1.06)), success rate (RR = 1.09 (0.96 – 1.24)), increase in root length (SMD = 0.25 (-0.14 – 0.63)), root width (0.66 (0.22 – 1.10)) and decrease in apical diameter (SMD =0.66 (-0.51 – 1.83)). Funnel plot did not show any heterogeneity indicating absence of publication bias. REP significantly improved apical root end closure. AP are equally effective in forming calcific barrier, however it was concluded that regeneration procedures are comparably superior to apexification procedures with greater outcomes. Clinicians should consider employing the REP in cases when root development is severely deficient and where tooth’s prognosis is hopeless even with an apexification procedure.