Search Results (85)

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

The intra- and intercellular signaling molecule nitric oxide (NO) is produced in endothelial cells by the activity of endothelial NO synthase (eNOS). Upon formation, NO diffuses into the underlying vascular smooth muscle cells, where it activates NO-sensitive guanylyl cyclase (NO-GC) resulting in the production of cyclic guanosine 3′,5′-monophosphate (cGMP) from guanosine 5′-triphosphate (GTP). Inducing vasodilatation, inhibiting platelet aggregation and leukocyte adhesion, and inhibiting the proliferation and migration of vascular smooth muscle cells, the NO-cGMP signaling leads to a number of anti-inflammatory processes. Inflammation-dependent elevated concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in blood vessels of inflamed dental pulp induce an uncoupling of eNOS and oxidized NO-GC, leading to a disruption of NO-cGMP signaling. Endothelial dysfunction in inflamed dental pulp alters cell–cell and cell–matrix interactions, reducing the regenerative and reparative potential of the dentin–pulp complex in response to carious lesions. In the therapeutic management of caries, it is essential to consider the presence of endothelial dysfunction in the inflamed dental pulp. The utilization of NO-GC stimulators and activators in indirect and direct pulp capping materials may enhance the regeneration and repair potential of inflamed dental pulp. Full article

Background: The treatment of cavitated lesions has evolved with minimally invasive dentistry (MID), whereby we can leave demineralized enamel that could potentially be remineralizable with the use of materials such as resin-modified glass ionomer cements (RMGICs) that allow these lesions to be repaired and remineralized while removing less tooth tissue. The aim of our study was to compare the influence of aging on adhesion to sound enamel, demineralized enamel, and the healthy dentin of five RMGICs (Vitremer^®, ACTIVA BioACTIVE Restorative, Riva LC, Ionolux^®, and GC Fuji II LC) and fluoride release. There are currently no studies on adhesion in demineralized enamel. Method: A total of 1035 bovine incisors were analyzed in 45 groups of 23 teeth each. The groups were established based on three factors: time (24 h, 1 month, and 3 months); substrate (sound enamel, demineralized enamel, and healthy dentin); and type of material. In each group, 20 samples underwent shear bond strength (SBS) and fracture type analysis. Adhesive interfaces were observed in three samples from each group using field emission scanning electron microscopy (FESEM). Daily and cumulative fluoride release rates were calculated. Results: Adhesion improved over time on both demineralized and sound enamel. ACTIVA BioACTIVE Restorative had the highest SBS values (33.63 ± 10.69 MPa), and Vitremer^® had the lowest (4.10 ± 4.63). Most fractures were adhesive. Vitremer^® and Ionolux^® showed the highest daily and cumulative fluoride release rates (Vitremer daily (24 h): 225.30 ± 26.28 ppm/g; Vitremer cumulative (30 days): 635.99 ± 305.38 ppm/g; Ionolux daily (24 h): 207.59 ± 48.43 ppm/g; Ionolux cumulative (30 days): 501.21 ± 138.71 ppm/g) and ACTIVA BioACTIVE Restorative showed the lowest (ACTIVA daily (24 h): 10.50 ± 0.85; ACTIVA cumulative (30 days): 39.10 ± 2.16). Conclusions: ACTIVA BioACTIVE Restorative was the material with the best adhesion values on all substrates and at all times, but it showed the lowest fluoride release rates. Full article

Introduction: Direct pulp capping (DPC) aims to preserve the vitality of the dental pulp by placing a protective biocompatible material over the exposed pulp tissue to facilitate healing. There are several calcium-silicate materials that have been designed to promote mineralization and the regulation of inflammation. These have strong potential for the repair and regeneration of dental pulp. Among them, Biodentine (BD) and EndoSequence RRM Putty (ES) have been found to promote in vitro and in vivo mineralization while minimizing some of the limitations of the first-generation calcium-silicate-based materials. Theracal-LC (TLC), a light-cured, resin-modified calcium-silicate material, is a newer product with potential to improve the clinical outcomes of DPC, but existing studies have reported conflicting findings regarding its biocompatibility and ability to support pulpal healing in direct contact with the pulp. A comprehensive assessment of the biocompatibility and pulpal protection provided by these three capping materials has not yet been performed. Aim: We aimed to quantify the inflammatory response, dentin bridge formation, and material adaptation following DPC using three calcium-silicate materials: ES, BD, and TLC. Materials and Methods: DPC was performed on the maxillary first molar of C57BL/6 female mice. Maxilla were collected and processed at 1 and 21 days post-DPC. The early inflammatory response was measured 24 h post-procedure using confocal imaging of anti-Lys6G6C, which indicates the extent of neutrophil and monocyte infiltration. Reparative mineralized bridge formation was assessed at 21 days post-procedure using high-resolution micro-computed tomography (micro-CT) and histology. Lastly, the homogeneity of the capping materials was evaluated by quantifying voids in calcium-silicate restorations using micro-CT. Results: DPC using TLC induced less infiltration of Lys6G6C⁺ cells at 24 h than BD or ES. BD promoted higher volumes of tertiary dentin than TLC, but TLC and ES showed no significant differences in volume. No differences were observed in material adaptation and void spaces among the three capping materials. Conclusions: All three materials under investigation supported pulp healing and maintained marginal integrity. However, TLC induced a lower inflammatory response on day 1 and induced similar levels of tertiary dentin to ES. These observations challenge the common perception that resin-based capping materials are not suitable for direct pulp capping. Our findings underscore the need to balance biological responses with physical properties when selecting pulp capping materials to improve long-term clinical success. Full article

Eucommia ulmoides Oliver (E. ulmoides), a traditional medicinal plant, has been widely used for its antioxidant and anti-inflammatory properties. However, its effects on dental tissue regeneration remain largely unexplored. In this study, we investigated the odontogenic potential of E. ulmoides extract in human dental pulp stem cells (hDPSCs). Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, and antioxidant activity was evaluated via the DPPH radical scavenging method. Odontoblast differentiation was examined using Alizarin Red S (ARS) staining, real-time PCR, and Western blot analysis of key differentiation markers, including dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP). Our results demonstrated that E. ulmoides extract enhanced mineralization and upregulated both gene and protein expression of odontoblast differentiation markers in a dose-dependent manner. Furthermore, signaling pathway analysis revealed that E. ulmoides extract activated the SMAD pathway while downregulating ERK and p38 MAPK phosphorylation during odontogenic differentiation. These findings suggest that E. ulmoides extract promotes odontoblast differentiation in hDPSCs and may serve as a promising natural agent for dental tissue regeneration. These findings further underscore its potential clinical relevance as a therapeutic candidate to enhance dental tissue repair and regeneration. Full article

Hydrogels have emerged as promising biomaterials for oral tissue regeneration thanks to their high-water content, excellent biocompatibility, and ability to mimic native tissue environments. These versatile materials can be tailored to support cell adhesion, proliferation, and differentiation, making them suitable for repairing both soft and hard oral tissues. When engineered from natural polymers and enriched with bioactive agents, hydrogels offer enhanced regenerative potential. Biopolymer-based hydrogels, derived from materials such as chitosan, alginate, collagen, hyaluronic acid, and gelatin, are particularly attractive due to their biodegradability, bioactivity, and structural similarity to the extracellular matrix, creating an optimal microenvironment for cell growth and tissue remodeling. Recent innovations have transformed these systems into multifunctional platforms capable of supporting targeted regeneration of periodontal tissues, alveolar bone, oral mucosa, dental pulp, and dentin. Integration of bioactive molecules, particularly essential oils, bio-derived constituents, cells, or growth factors, has introduced intrinsic antimicrobial, anti-inflammatory, and antioxidant functionalities, addressing the dual challenge of promoting tissue regeneration while at the same time attenuating microbial contamination in the oral environment. This review explores the design strategies, material selection, functional properties, and biomedical applications in periodontal therapy, guided tissue regeneration, and implant integration of natural polymer-based hydrogels enriched with bioactive factors, highlighting their role in promoting oral tissue regeneration. In addition, we discuss current challenges related to mechanical stability, degradation rates, and clinical translation, while highlighting future directions for optimizing these next-generation bioactive hydrogel systems in regenerative dentistry. Full article

Reparative tertiary dentinogenesis requires the recruitment and odontogenic differentiation of dental pulp stem cells (DPSCs). Extracellular vesicles (EVs) as bioactive molecules have gained attention in regenerative medicine for their ability to mediate tissue repair through intercellular communication, influencing cell recruitment, proliferation, and differentiation. This study aimed to evaluate the effects of EVs on DPSC homing and odontogenic differentiation for dentin regeneration. DPSC-derived EVs were cultured in either growth (EV-G) or odontogenic differentiation (EV-O) conditions and isolated using a modified precipitation method. EVs were characterized by nanoparticle tracking analysis, scanning electron microscopy, antibody array, and cellular uptake assay. Treatment with 5 × 10⁸ EVs/mL significantly enhanced DPSC chemotaxis and proliferation compared with a no-treatment control and a lower dosage of EV (5 × 10⁷ EVs/mL). Gene expression and biochemical analyses revealed that EV-O up-regulated odontogenic markers including collagen type 1A1 (COL1A1), runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALP). EV-O enhanced dentin regeneration by approximately 55% over vehicle controls in a rabbit partial dentinotomy/pulpotomy model. We identified key microRNAs (miR-21-5p, miR-221-3p, and miR-708-3p) in EV-O involved in cell homing and odontogenesis. In conclusion, our EV-based cell homing and odontogenic differentiation strategy has significant therapeutic potential for dentin regeneration. Full article

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

In this in vitro study, we compare the discoloration potential of three premixed calcium silicate cements, specifically EndoCem MTA Premixed, Bio-C Repair, and NeoPUTTY, when applied with or without two surface pretreatments (Nd-YAG laser irradiation or dentin-bonding agents). One hundred extracted human maxillary incisors were allocated into ten groups (n = 10), including the untreated control group. A standard access cavity was prepared in all teeth except the control group. Groups were formed according to the type of premixed calcium silicate cement used and the surface pretreatment applied to the internal surfaces of the cavities. Color measurements were taken with a VITA Easyshade Advance 5.0 spectrophotometer and converted to ΔE values using the CIEDE2000 formula at baseline (T0) and 7 (T1), 30 (T2), 90 (T3), and 180 (T4) days. Data were analyzed using the Shapiro–Wilk test to assess normality, followed by the Friedman and Kruskal–Wallis tests for within- and between-group comparisons, respectively (α = 0.05). No statistically or clinically significant differences in ${∆\mathrm{E}}_{00}$ were detected among materials, surface treatments, or timepoints (p > 0.05). All mean ${∆\mathrm{E}}_{00}$ values remained below the perceptibility threshold (3.5). Within the limitations of this 180-day in vitro model, the tested materials showed favorable short-term color stability, and neither the Nd-YAG laser nor the dentin-bonding agents altered the outcomes. Long-term in vivo studies are required to recommend their clinical use in aesthetically critical areas. Full article

Advanced bioengineering, popularly known as regenerative dentistry, has emerged and is steadily developing with the aim of replacement of lost or injured tissues in the mouth using stem cells and other biomaterials. Conventional therapies for reparative dentistry, for instance fillings or crowns, mainly entail the replenishment of affected tissues without much concern given to the regeneration of tissues. However, these methods do not enable the natural function and aesthetics of the teeth to be maintained in the long term. There are several regenerative strategies that offer the potential to address these limitations to the extent of biologically restoring the function of teeth and their components, like pulp, dentin, bone, and periodontal tissues. Hence, stem cells, especially dental tissue derived stem cells, such as dental pulp stem cells, periodontal ligament stem cells, or apical papilla stem cells, are quite promising in this regard. These stem cells have the potentiality of generating precise dental cell lineages and thus are vital for tissue healing and renewal. Further, hydrogels, growth factors, and synthetic scaffolds help in supporting the stem cells for growth, proliferation, and differentiation into functional tissues. This review aims at describing the process of stem cell-based tissue repair biomaterials in dental regeneration, and also looks into the practice and prospects of regenerative dentistry, analysing several case reports and clinical investigations that demonstrate the efficacy and limitations of the technique. Nonetheless, the tremendous potential for regenerative dentistry is a reality that is currently challenged by biological and technical constraints, such as scarcity of stem cell sources, inadequate vascularization, and the integration of the materials used in the procedure. As we move forward, the prospects for regenerative dentistry are in subsequent developments of stem cell technology, biomaterial optimization, and individualized treatment methods, which might become increasingly integrated in dental practices globally. However, there are regulatory, ethical and economic issues that may pose a hurdle in the further advancement of this discipline. Full article

A new type of glass fiber (GF)-reinforced bio-derived polybenzoxazine (GF/bio-derived PBz) composites suitable for dental post applications was developed. The study assessed the effects of different quantities of GF on the mechanical and thermal characteristics, thermal stability, and flame resistance of the composite samples. Additionally, the feasibility of using GF/bio-derived PBz composites for dental posts was analyzed through finite element analysis (FEA). The stress distribution in a tooth model repaired with the newly developed GF/bio-derived PBz composite posts under oblique loads was compared to models repaired with conventional glass fiber post and gold alloy post. The incorporation of GFs significantly enhanced the flexural properties, thermal stability, and flame resistance of the composite samples, while also reducing thermal expansion in a manner that closely matched that of dentin. The FEA of a tooth model repaired with a composite post derived from GF/bio-based PBz revealed a stress distribution pattern comparable to that of a tooth model repaired using a conventional glass fiber post. Considering the composite’s mechanical properties, thermal stability, flame resistance, and its suitability for dental fiber posts as demonstrated by the FEA, the GF/bio-derived PBz holds significant promise for use in dental fiber post applications. Full article

The advancement of Vital Pulp Therapy (VPT) in dentistry has shown remarkable progress, with a focus on innovative materials and scaffolds to facilitate reparative dentin formation and tissue regeneration. A comprehensive search strategy was performed across PubMed, Scopus, and Web of Science using keywords such as “vital pulp therapy”, “biomaterials”, “dentin regeneration”, and “growth factors”, with filters for English language studies published in the last 10 years. The inclusion criteria focused on in vitro, in vivo, and clinical studies evaluating traditional and next-generation biomaterials for pulp capping and tissue regeneration. Due to the limitations of calcium-based cements in tissue regeneration, next-generation biomaterials like gelatin, chitosan, alginate, platelet-rich fibrins (PRF), demineralized dentin matrix (DDM), self-assembling peptides, and DNA-based nanomaterials were explored for their enhanced biocompatibility, antibacterial properties, and regenerative potential. These biomaterials hold great potential in enhancing VPT outcomes, but further research is required to understand their efficacy and impact on dentin reparative properties. This review explores the mechanisms and properties of biomaterials in dentin tissue regeneration, emphasizing key features that enhance tissue regeneration. These features include biomaterial sources, physicochemical properties, and biological characteristics that support cells and functions. The discussion also covers the biomaterials’ capability to encapsulate growth factors for dentin repair. The development of innovative biomaterials and next-generation scaffold materials presents exciting opportunities for advancing VPT in dentistry, with the potential to improve clinical outcomes and promote tissue regeneration in a safe and effective manner. Full article

Peptide-based biomimetic treatments have gained increased attention in the dental field due to their biocompatibility and minimally invasive qualities. These biomimetic approaches can replicate the native architecture of dental tissues, thus contributing to higher success rates and improved longevity of restorations. The aim of this study was first to examine the biocompatibility and stability of an amelogenin peptide-based chitosan hydrogel (P26-CS) against salivary enzymes. Second, we aimed to evaluate its efficacy in biomimetically repairing human dental lesions in situ. White spot lesions (WSLs) in enamel and non-carious cervical lesions (NCCLs) in dentin were artificially created. Chitosan (CS) improved peptide stability, while remineralization of enamel sections with P26-CS was not impeded by salivary enzymes. The peptide was not cytotoxic, irritating, or sensitizing. Fluorescently labeled P26-CS penetrated ~300 μm into the enamel of WSLs and ~100 μm into the dentin of NCCLs. After peptide treatment, quantitative light-induced fluorescence (QLF) and microcomputed tomography (μCT) indicated a gain in mineral density of WSLs. In NCCLs, scanning electron microscopy showed that the dentin was covered by a mineral layer of needle-shaped crystals. Our results show that the repair of artificial WSLs and NCCLs was achieved by P26 peptide-guided remineralization and demonstrate its potential to repair dental lesions. Full article

With the paradigm shift towards minimally invasive biologic therapies, vital pulp therapy (VPT) has been receiving increasing attention. Currently, bioactive materials (BMs), including MTAs, Biodentine, Bioaggregate, and iRoot BP Plus, are clinically widely used for the repair of damaged pulp tissue. Emerging evidence highlights the crucial role of inflammation in pulp repair, with mild to moderate inflammation serving as a prerequisite for promoting pulp repair. BMs play a pivotal role in regulating the balance between inflammatory response and reparative events for dentine repair. Despite their widespread application as pulp-capping agents, the precise mechanisms underlying the actions of BMs remain poorly understood. A comprehensive literature review was conducted, covering studies on the inflammatory responses induced by BMs published up to December 2023. Sources were identified through searches of PubMed and MEDLINE databases, supplemented by manual review of cross-references from relevant studies. The purpose of this article is to discuss diverse mechanisms by which BMs may regulate the balance between tissue inflammation and repair. A deeper understanding of these regulatory mechanisms will facilitate the optimization of current pulp-capping agents, enabling the development of targeted regenerative strategies to achieve superior clinical outcomes. Full article

Cell homing, a process that leverages the body’s natural ability to recruit cells and repair damaged tissues, presents a promising alternative to cell transplantation methods. Central to this approach is the recruitment of endogenous stem/progenitor cells—such as those from the apical papilla, bone marrow, and periapical tissues—facilitated by chemotactic biological cues. Moreover, biomaterial scaffolds embedded with signaling molecules create supportive environments, promoting cell migration, adhesion, and differentiation for the regeneration of the pulp–dentin complex. By analyzing in vivo animal studies using cell homing strategies, this review explores how biomolecules and scaffold materials enhance the recruitment of endogenous stem cells to the site of damaged dental pulp tissue, thereby promoting repair and regeneration. It also examines the key principles, recent advancements, and current limitations linked to cell homing-based regenerative endodontic therapy, highlighting the interplay of biomaterials, signaling molecules, and their broader clinical implications. Full article