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17 pages, 3105 KiB  
Article
Cell Viability of Wharton’s Jelly-Derived Mesenchymal Stem Cells (WJ-MSCs) on 3D-Printed Resins for Temporary Dental Restorations
by Mónica Antonio-Flores, Andrés Eliú Castell-Rodríguez, Gabriela Piñón-Zárate, Beatriz Hernández-Téllez, Abigailt Flores-Ledesma, Enrique Pérez-Martínez, Carolina Sámano-Valencia, Gerardo Quiroz-Petersen and Katia Jarquín-Yáñez
J. Compos. Sci. 2025, 9(8), 404; https://doi.org/10.3390/jcs9080404 - 1 Aug 2025
Viewed by 434
Abstract
There is insufficient evidence regarding the cytotoxicity of restorative 3D-printing resins, used as part of the digital workflow in dentistry. This study presents a novel comparative evaluation of cell viability and adhesion using human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), a less commonly [...] Read more.
There is insufficient evidence regarding the cytotoxicity of restorative 3D-printing resins, used as part of the digital workflow in dentistry. This study presents a novel comparative evaluation of cell viability and adhesion using human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), a less commonly used but clinically relevant cell line in dental biomaterials research. The aim of this study was to evaluate the cell viability of WJ-MSCs seeded on 3D-printed resins intended for temporary restorations. Resin discs of three commercial 3D-printing resins (NextDent C&B, Leaf Dental C&B, and UNIZ Temp) and a conventional self-curing acrylic resin (NicTone) were used. WJ-MSCs were cultured on the specimens for 1, 4, and 10 days. Cell viability was assessed using the PrestoBlue assay, Live/Dead immunofluorescence staining, and 7AAD/Annexin V staining. Cell adhesion was evaluated using scanning electron microscopy. Direct exposure to the 3D-printed resins and the self-curing acrylic caused slight reductions in cell viability compared to the control group in both microscopic analyses. 7AAD/Annexin V showed the highest percentage of viable WBCs for the conventional acrylic (34%), followed by UNIZ (35%), NextDent (42%), and Leaf Dental (36%) (ANOVA p < 0.05 Tukey’s post-hoc test p < 0.05). These findings suggest that 3D-printed resins could be considered safe for use in temporary restorations. Full article
(This article belongs to the Section Biocomposites)
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20 pages, 1220 KiB  
Systematic Review
The Evolving Role of Stem Cells in Oral Health and Regeneration: A Systematic Review
by Gianna Dipalma, Grazia Marinelli, Arianna Fiore, Liviana Balestriere, Claudio Carone, Silvio Buongiorno, Francesco Inchingolo, Giuseppe Minervini, Andrea Palermo, Angelo Michele Inchingolo and Alessio Danilo Inchingolo
Surgeries 2025, 6(3), 65; https://doi.org/10.3390/surgeries6030065 - 30 Jul 2025
Viewed by 337
Abstract
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing [...] Read more.
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article
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18 pages, 2876 KiB  
Article
The Secretome of Human Deciduous Tooth-Derived Mesenchymal Stem Cells Enhances In Vitro Wound Healing and Modulates Inflammation
by Thais Simião Payão, Vanessa Pellegrini, Joseane Morari, Gisele Mara Silva Gonçalves, Maria Carolina Ximenes de Godoy, Alessandra Gambero, Leonardo O. Reis, Lício Augusto Velloso, Eliana Pereira Araújo and Lívia Bitencourt Pascoal
Pharmaceutics 2025, 17(8), 961; https://doi.org/10.3390/pharmaceutics17080961 - 25 Jul 2025
Viewed by 358
Abstract
Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) [...] Read more.
Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article
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15 pages, 1429 KiB  
Article
Extracellular Vesicles-Induced Cell Homing and Odontogenesis via microRNA Signaling for Dentin Regeneration
by Venkateswaran Ganesh, Douglas C. Fredericks, Emily B. Petersen, Henry L. Keen, Rui He, Jordon D. Turner, James A. Martin, Aliasger K. Salem, Kyungsup Shin, Abhishek Parolia and Dongrim Seol
Int. J. Mol. Sci. 2025, 26(15), 7182; https://doi.org/10.3390/ijms26157182 - 25 Jul 2025
Viewed by 190
Abstract
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. [...] Read more.
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
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14 pages, 1895 KiB  
Article
MicroRNA Signatures in Dental Pulp Stem Cells Following Nicotine Exposure
by David Vang, Leyla Tahrani Hardin, Nabil Abid, Der Thor and Nan Xiao
Dent. J. 2025, 13(8), 338; https://doi.org/10.3390/dj13080338 - 23 Jul 2025
Viewed by 274
Abstract
Background and Objectives: Nicotine is the most well-studied toxic substance in cigarette smoke and e-cigarette vape. However, smoke and vape are composed of other components that have a negative impact on health. The objective of this study is to investigate whether nicotine has [...] Read more.
Background and Objectives: Nicotine is the most well-studied toxic substance in cigarette smoke and e-cigarette vape. However, smoke and vape are composed of other components that have a negative impact on health. The objective of this study is to investigate whether nicotine has a distinctive impact on molecular mechanisms in stem cells. Methods: The cellular impact of nicotine on the regenerative capacity of human dental pulp stem cells (DPSCs) and the microRNA (miRNA) profile was examined. Bioinformatic analysis was performed to identify miRNA-regulated cellular pathways associated with nicotine exposure. These pathways were then compared to those induced by cigarette smoke condensate (CSC). Results: Prolonged exposure to nicotine significantly impaired the regeneration of DPSCs and changed the expression of miRNAs. Nicotine upregulated the expression of hsa-miR-7977, hsa-miR-3178, and hsa-miR-10400-5p compared to vehicle control. Interestingly, nicotine did not change the expression of hsa-miR-29b-3p, hsa-miR-199b-5p, hsa-miR-26b-5p, or hsa-miR-26a-5p compared to the control. However, the expressions of these miRNAs were significantly altered when compared to CSC treatment. Further analysis revealed that nicotine was distinctively associated with certain miRNA-targeted pathways including apoptosis, ErbB, MAPK signaling, PI3K-Akt, TGF-b signaling, and Wnt signaling. Conclusions: Our work provides evidence on the distinctive miRNA signature induced by nicotine. The information will be important for identifying the unique molecular pathways downstream of nicotine from smoking and vaping in different individuals, providing a new direction for personalized disease prevention, prognosis, and treatment. Full article
(This article belongs to the Special Issue Recreational Drugs, Smoking, and Their Impact on Oral Health)
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20 pages, 6191 KiB  
Article
Functional Assessment of Microplasma-Sprayed Hydroxyapatite-Zirconium Bilayer Coatings: Mechanical and Biological Perspectives
by Sergii Voinarovych, Serhiy Maksimov, Sergii Kaliuzhnyi, Oleksandr Kyslytsia, Yuliya Safarova (Yantsen) and Darya Alontseva
Materials 2025, 18(14), 3405; https://doi.org/10.3390/ma18143405 - 21 Jul 2025
Viewed by 242
Abstract
Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also [...] Read more.
Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr–HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. Full article
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20 pages, 4241 KiB  
Article
Strontium-Doped Ti3C2Tx MXene Coatings on Titanium Surfaces: Synergistic Osteogenesis Enhancement and Antibacterial Activity Evaluation
by Yancheng Lai and Anchun Mo
Coatings 2025, 15(7), 847; https://doi.org/10.3390/coatings15070847 - 19 Jul 2025
Viewed by 393
Abstract
To improve implant osseointegration while preventing infection, we developed a strontium (Sr)-doped Ti3C2Tx MXene coating on titanium, aiming to synergistically enhance bone integration and antibacterial performance. MXene is a family of two-dimensional transition-metal carbides/nitrides whose abundant surface terminations [...] Read more.
To improve implant osseointegration while preventing infection, we developed a strontium (Sr)-doped Ti3C2Tx MXene coating on titanium, aiming to synergistically enhance bone integration and antibacterial performance. MXene is a family of two-dimensional transition-metal carbides/nitrides whose abundant surface terminations endow high hydrophilicity and bioactivity. The coating was fabricated via anodic electrophoretic deposition (40 V, 2 min) of Ti3C2Tx nanosheets, followed by SrCl2 immersion to incorporate Sr2+. The coating morphology, phase composition, chemistry, hydrophilicity, mechanical stability, and Sr2+ release were characterized. In vitro bioactivity was assessed with rat bone marrow mesenchymal stem cells (BMSCs)—with respect to viability, proliferation, migration, alkaline phosphatase (ALP) staining, and Alizarin Red S mineralization—while the antibacterial efficacy was evaluated against Staphylococcus aureus (S. aureus) via live/dead staining, colony-forming-unit enumeration, and AlamarBlue assays. The Sr-doped MXene coating formed a uniform lamellar structure, lowered the water-contact angle to ~69°, and sustained Sr2+ release (0.36–1.37 ppm). Compared to undoped MXene, MXene/Sr enhanced BMSC proliferation on day 5, migration by 51%, ALP activity and mineralization by 47%, and reduced S. aureus viability by 49% within 24 h. Greater BMSCs activity accelerates early bone integration, whereas rapid bacterial suppression mitigates peri-implant infection—two critical requirements for implant success. Sr-doped Ti3C2Tx MXene thus offers a simple, dual-function surface-engineering strategy for dental and orthopedic implants. Full article
(This article belongs to the Section Surface Coatings for Biomedicine and Bioengineering)
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12 pages, 3535 KiB  
Article
TiN-Ag Multilayer Protective Coatings for Surface Modification of AISI 316 Stainless Steel Medical Implants
by Božana Petrović, Dijana Mitić, Minja Miličić Lazić, Miloš Lazarević, Anka Trajkovska Petkoska, Ilija Nasov, Slavoljub Živković and Vukoman Jokanović
Coatings 2025, 15(7), 820; https://doi.org/10.3390/coatings15070820 - 14 Jul 2025
Viewed by 328
Abstract
Stainless steel (SS) is one of the materials most commonly utilized for fabrication of medical implants and its properties are often improved by deposition of protective coatings. This study investigates certain physico-chemical and biological properties of SS substrate coated with multilayer thin film [...] Read more.
Stainless steel (SS) is one of the materials most commonly utilized for fabrication of medical implants and its properties are often improved by deposition of protective coatings. This study investigates certain physico-chemical and biological properties of SS substrate coated with multilayer thin film consisting of titanium nitride and silver layers (TiN-Ag film). TiN-Ag films were deposited on the surface of AISI 316 SS substrate by a combination of cathodic arc evaporation and DC magnetron sputtering. SS substrate was analyzed by TEM, while deposited coatings were analyzed by SEM, EDS and wettability measurements. Also, mitochondrial activity assay, and osteogenic and chondrogenic differentiation were performed on dental pulp stem cells (DPSCs). SEM and EDS revealed excellent adhesion between coatings’ layers, with the top layer predominantly composed of Ag, which is responsible for antibacterial properties. TiN-Ag film exhibited moderately hydrophilic behaviour which is desirable for orthopedic implant applications. Biological assays revealed significantly higher mitochondrial activity and enhanced osteogenic and chondrogenic differentiation of DPSC on TiN-Ag films compared to TiN films. The newly designed TiN-Ag coatings showed a great potential for the surface modification of SS implants, and further detailed investigations will explore their suitability for application in clinical practice. Full article
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22 pages, 4137 KiB  
Article
Biocompatibility of Hydraulic Calcium Silicate-Based Cement MTA FlowTM on Human Dental Pulp Stem Cells In Vitro
by Paulius Tušas, Josette Camilleri, Milda Alksnė, Egidijus Šimoliūnas, Saulius Drukteinis, Eglė Marija Urbonė, Virginija Bukelskienė, Vygandas Rutkūnas and Vytautė Pečiulienė
J. Funct. Biomater. 2025, 16(7), 252; https://doi.org/10.3390/jfb16070252 - 7 Jul 2025
Viewed by 869
Abstract
Aim: hydraulic calcium silicate-based cements (HCSCs) are widely used in endodontics for vital pulp therapy and other clinical procedures due to their favorable physicochemical and biological properties. This study evaluates the biological properties of two HCSCs—MTA Flow™ and MTA Flow™ White (in a [...] Read more.
Aim: hydraulic calcium silicate-based cements (HCSCs) are widely used in endodontics for vital pulp therapy and other clinical procedures due to their favorable physicochemical and biological properties. This study evaluates the biological properties of two HCSCs—MTA Flow™ and MTA Flow™ White (in a 3:2 liquid-to-powder ratio, thick consistency)—on human dental pulp stem cells (hDPSCs). Methodology: hDPSCs were exposed to leachates from MTA Flow™, MTA Flow™ White, and ProRoot® MTA. pH changes, cytotoxicity, cell proliferation, cell morphology, and cell death (apoptosis/necrosis) were assessed in vitro. Results: MTA Flow™ White and ProRoot® MTA leachates produced a strongly alkaline pH (~10–12) compared to the negative control, whereas MTA Flow™ leachate caused a smaller pH increase (~9.4). Freshly mixed cements showed moderate cytotoxicity (around 40–60% cell viability at 100% concentration), while hardened cement leachates did not significantly affect cell viability. At 100% concentration, MTA Flow™ and MTA Flow™ White leachates significantly inhibited hDPSC proliferation and caused cell death, but at lower concentrations (≤50%) they supported cell viability and proliferation comparable to ProRoot® MTA. hDPSCs exposed to MTA Flow™ and MTA Flow™ White leachates appeared more elongated morphologically than those exposed to ProRoot® MTA. Notably, cells treated with MTA Flow™ White leachates were significantly smaller than those treated with MTA Flow™. Conclusions: MTA Flow™ and MTA Flow™ White, used in 3:2 thick consistency, demonstrated biocompatibility comparable to ProRoot® MTA in vitro. While 100% leachates showed moderate cytotoxicity, lower concentration dilutions (≤50%) supported hDPSC viability, proliferation, and morphology. These findings support their potential as safe alternatives for vital pulp therapy. Further in vivo studies and dynamic models are needed to confirm long-term biological performance. Full article
(This article belongs to the Special Issue Role of Dental Biomaterials in Promoting Oral Health)
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20 pages, 1658 KiB  
Article
Preclinical In Vitro Evaluation of Extracellular Vesicles from Human Dental Pulp Stem Cells for the Safe and Selective Modulation of Anaplastic Thyroid Carcinoma
by Anderson Lucas Alievi, Michelli Ramires Teixeira, Vitor Rodrigues da Costa, Irina Kerkis and Rodrigo Pinheiro Araldi
Int. J. Mol. Sci. 2025, 26(13), 6443; https://doi.org/10.3390/ijms26136443 - 4 Jul 2025
Viewed by 391
Abstract
Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Precision oncology seeks personalized therapies that selectively modulate tumor behavior, which is critical for improving patient outcomes. In this study, we evaluated the therapeutic potential of human [...] Read more.
Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Precision oncology seeks personalized therapies that selectively modulate tumor behavior, which is critical for improving patient outcomes. In this study, we evaluated the therapeutic potential of human dental pulp stem cell-derived extracellular vesicles (hDPSC-EVs) in three ATC cell lines (8505C, HTH83, KTC-2). Fluorescence and confocal microscopy confirmed the efficient, time-dependent internalization of hDPSC-EVs by ATC cells, with increased fluorescence intensity over 48 h. Functional assays revealed the selective inhibition of migration and invasion in a cell line-dependent manner, without affecting cell proliferation, viability, or tumorigenic traits, indicating a non-cytotoxic, context-specific modulation of tumor behavior. After 72 h of EV treatment, targeted qPCR of 92 cancer-related genes showed the strongest response in 8505C cells (24 genes; 16 up, 8 down), moderate changes in KTC-2 (16 genes; 14 up, 2 down), and few alterations in HTH83 (6 genes; 4 up, 2 down). Across all lines, FN1 emerged as a context-dependent target, downregulated in 8505C but upregulated in the other two. No broad pathway enrichment was observed, indicating the fine-tuning of key networks rather than wholesale reprogramming. Despite variations across cell lines, hDPSC-EVs consistently demonstrated no impact on cell proliferation and no evidence of cytotoxicity or tumorigenic behavior, with no adverse outcomes. These findings provide preclinical evidence for hDPSC-EVs as a promising, safe, and targeted therapeutic platform in precision oncology, particularly for aggressive cancers, like ATC, warranting further exploration in preclinical and clinical studies. Full article
(This article belongs to the Special Issue Preclinical and Translational Research in Thyroid Cancer)
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19 pages, 937 KiB  
Review
Tissue Repair Mechanisms of Dental Pulp Stem Cells: A Comprehensive Review from Cutaneous Regeneration to Mucosal Healing
by Jihui He, Jiao Fu, Ruoxuan Wang, Xiaojing Liu, Juming Yao, Wenbo Xing, Xinxin Wang and Yan He
Curr. Issues Mol. Biol. 2025, 47(7), 509; https://doi.org/10.3390/cimb47070509 - 2 Jul 2025
Viewed by 674
Abstract
Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp [...] Read more.
Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article
(This article belongs to the Section Molecular Medicine)
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21 pages, 3621 KiB  
Article
Dual-Mode Antibacterial Orthodontic Composite: Contact-Killing QACs and Sustained CHX Release via Large-Pore Mesoporous Silica Nanoparticles
by Xiaotian Teng, Yingguang Cao, Jing Mao and Xiaojuan Luo
Int. J. Mol. Sci. 2025, 26(13), 6172; https://doi.org/10.3390/ijms26136172 - 26 Jun 2025
Viewed by 393
Abstract
This study develops a dual-mode antibacterial orthodontic adhesive by integrating quaternary ammonium salt-modified large-pore mesoporous silica nanoparticles (QLMSN@CHX). The material integrates two antibacterial mechanisms: (1) contact killing via covalently anchored quaternary ammonium salts (QACs) and (2) sustained release of chlorhexidine (CHX) from radially [...] Read more.
This study develops a dual-mode antibacterial orthodontic adhesive by integrating quaternary ammonium salt-modified large-pore mesoporous silica nanoparticles (QLMSN@CHX). The material integrates two antibacterial mechanisms: (1) contact killing via covalently anchored quaternary ammonium salts (QACs) and (2) sustained release of chlorhexidine (CHX) from radially aligned macropores. The experimental results demonstrated that QLMSN@CHX (5 wt%) achieved rapid biofilm eradication (near-complete biofilm eradication at 24 h) and prolonged antibacterial activity, while maintaining shear bond strength comparable to commercial adhesives (6.62 ± 0.09 MPa after 30-day aging). The large-pore structure enabled controlled CHX release without burst effects, and covalent grafting ensured negligible QAC leaching over 30 days. The composite demonstrated good biocompatibility with human dental pulp mesenchymal stem cells at clinically relevant concentrations. This dual-mode design provides a clinically viable strategy to combat bacterial contamination in orthodontic treatments, with potential applications in other oral infections. Future studies will focus on validating efficacy in complex in vivo biofilm models. Full article
(This article belongs to the Special Issue The Advances in Antimicrobial Biomaterials)
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12 pages, 3419 KiB  
Article
Graphene Oxide-Enriched Polymer: Impact on Dental Pulp Cell Viability and Differentiation
by Magdalena Vega-Quiroz, Agustin Reyes-Maciel, Christian Andrea Lopez-Ayuso, Carlos A. Jurado, Hector Guzman-Juarez, Carlos Andres Alvarez-Gayosso, Benjamin Aranda-Herrera, Abdulrahman Alshabib and Rene Garcia-Contreras
Polymers 2025, 17(13), 1768; https://doi.org/10.3390/polym17131768 - 26 Jun 2025
Viewed by 493
Abstract
Background: Reconstructing maxillofacial defects is important in dentistry, so efforts are being made to develop materials that promote cell migration and repair. Graphene oxide (GO) is used to enhance the biocompatibility of polymethylmethacrylate (PMMA) due to its nanostructure. Objective: to assess cytotoxicity, cell [...] Read more.
Background: Reconstructing maxillofacial defects is important in dentistry, so efforts are being made to develop materials that promote cell migration and repair. Graphene oxide (GO) is used to enhance the biocompatibility of polymethylmethacrylate (PMMA) due to its nanostructure. Objective: to assess cytotoxicity, cell proliferation, and differentiation of human dental pulp stem cells (hDPSC) in response to a conventional PMMA (PMMA) and polymer enriched with GO (PMMA+GO). Methods: Experiments were carried out with primary hDPSC subcultures. The PMMA and PMMA+GO were tested in direct and indirect contact. Cytotoxicity (1 day) and proliferation (3, 7, and 14 days) were evaluated with an MTT bioassay. The osteogenic, adipogenic, and chondrogenic aspects were determinate with alizarin red, oil red, and safranine. Mean values, standard deviation, and percentages were calculated; data were analyzed with Shapiro–Wilks normality and Student’s t-test. Results: The cell viability of PMMA and PMMA+GO in direct contact correspond to 90.8 ± 6.2, 149.6 ± 14.5 (1 day); 99.9 ± 7.0, 95.7 ± 6.1 (3 days); 120.2 ± 14.6, 172.9 ± 16.2 (7 days); and 102.9 ± 17.3, 95.4 ± 22.8 (14 days). For indirect contact, 77.2 ± 8.4, 99 ± 21.4 (1 day); 64.8 ± 21.6, 67.0 ± 9.6 (3 days); 91.4 ± 16.5, 142 ± 18.7 (7 days); and 63 ± 15.8, 79.1 ± 3.1 (14 days). PMMA+GO samples showed enhanced adipogenic, chondrogenic, and osteogenic aspects. Conclusions: The integration of GO into PMMA biopolymers stimulates cell proliferation and differentiation, holding great promise for future applications in the field of biomedicine. Full article
(This article belongs to the Special Issue Challenges and Opportunities of Polymer Materials in Dentistry)
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20 pages, 3181 KiB  
Review
Therapeutic Applications of Dental Mesenchymal Stem Cells in Alzheimer’s Disease—A Scoping Review
by Rupali Agnihotri and Sumit Gaur
Dent. J. 2025, 13(7), 288; https://doi.org/10.3390/dj13070288 - 26 Jun 2025
Viewed by 649
Abstract
Background/Objectives: Alzheimer’s disease (AD), a neurodegenerative condition, produces dementia and cognitive debility. Lately, preclinical models of AD have shown neuroregenerative potential of mesenchymal stem cells of dental origin (DMSC). This scoping review aims to map and synthesize the evidence on the therapeutic applications [...] Read more.
Background/Objectives: Alzheimer’s disease (AD), a neurodegenerative condition, produces dementia and cognitive debility. Lately, preclinical models of AD have shown neuroregenerative potential of mesenchymal stem cells of dental origin (DMSC). This scoping review aims to map and synthesize the evidence on the therapeutic applications of DMSCs in AD management. Methods: This review followed the Arksey and O’Malley framework for scoping reviews and PRISMA-ScR guidelines. Scopus, Medline (Pubmed), Web of Science, and Embase databases were searched for published literature until February 2025. Data was mapped according to the type of DMSC and their therapeutic properties useful in AD management, like neuro differentiation, neuroprotection through increased neuron number and vitality, anti-neuroinflammation, mitochondrial repair, and improved cognition. Results: A total of 22 articles were included. A research gap existed, as most studies were preclinical (in vitro and animal models) with no clinical trials in humans. Furthermore, they mostly evaluated neuroregenerative properties of dental pulp stem cells (DPSC) and stem cells from human-exfoliated deciduous teeth (SHED), while Periodontal ligament stem cells (PDLSC) were least studied. All the DMSCs were neuroprotective and increased neuron number and vitality. Neurodifferentiation was reported in DPSCs and PDLSCs, while DPSCs and SHEDs showed anti-neuroinflammation, mitochondrial repair, and improved cognition in AD animal models. Conclusions: Although the DPSCs and SHEDs showed promising outcomes in preclinical models of AD, a gap exists as results have not been translated into human clinical trials. Future advances may identify plausible ways of applying the DMSCs to regain the lost neurons and re-establish a healthy brain microenvironment. Full article
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19 pages, 4384 KiB  
Article
Porous Osteoplastic Composite Materials Based on Alginate–Pectin Complexes and Cation-Substituted Hydroxyapatites
by Galina A. Davydova, Inna V. Fadeeva, Elena S. Trofimchuk, Irina I. Selezneva, Muhriddin T. Mahamadiev, Lenar I. Akhmetov, Daniel S. Yakovsky, Vadim P. Proskurin, Marco Fosca, Viktoriya G. Yankova, Julietta V. Rau and Vicentiu Saceleanu
Polymers 2025, 17(13), 1744; https://doi.org/10.3390/polym17131744 - 23 Jun 2025
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Abstract
Novel three-dimensional porous composites of alginate–pectin (A/P) with zinc- or manganese-substituted hydroxyapatites (A/P-ZnHA and A/P-MnHA) were synthesized via lyophilization and calcium cross-linking. Powder X-ray diffraction and infrared spectroscopy analyses confirmed single-phase apatite formation (crystallite sizes < 1 µm), with ZnHA exhibiting lattice contraction [...] Read more.
Novel three-dimensional porous composites of alginate–pectin (A/P) with zinc- or manganese-substituted hydroxyapatites (A/P-ZnHA and A/P-MnHA) were synthesized via lyophilization and calcium cross-linking. Powder X-ray diffraction and infrared spectroscopy analyses confirmed single-phase apatite formation (crystallite sizes < 1 µm), with ZnHA exhibiting lattice contraction (*c*-axis: 6.881 Å vs. 6.893 Å for HA). Mechanical testing revealed tunable properties: pristine A/P sponges exhibited an elastic modulus of 4.7 MPa and a tensile strength of 0.10 MPa, reduced by 30–70% by HA incorporation due to increased porosity (pore sizes: 112 ± 18 µm in the case of MnHA vs. 148 ± 23 µm-ZnHA). Swelling capacity increased 2.3–2.8-fold (125–155% vs. 55% for A/P), governed by polysaccharide interactions. Scanning electron microscopy investigation showed microstructural evolution from layered A/P (<100 µm) to tridimensional architectures with embedded mineral particles. The A/P-MnHA composites demonstrated minimal cytotoxicity for the NCTC cells and good viability of dental pulp stem cells, while A/P-ZnHA caused ≈20% metabolic suppression, attributed to hydrolysis-induced acidification. Antibacterial assays highlighted A/P-MnHA′s broad-spectrum efficacy against Gram-positive (Bacillus atrophaeus) and Gram-negative (Pseudomonas protegens) strains, whereas A/P-ZnHA targeted only the Gram-positive strain. The developed composite sponges combine cytocompatibility and antimicrobial activity, potentially advancing osteoplastic materials for bone regeneration and infection control in orthopedic/dental applications. Full article
(This article belongs to the Special Issue Functional Polymer Composites: Synthesis and Application)
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