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Acta Biomaterialia Jan 2024Pulp capping is a necessary procedure for preserving the vitality and health of the dental pulp, playing a crucial role in preventing the need for root canal treatment...
Pulp capping is a necessary procedure for preserving the vitality and health of the dental pulp, playing a crucial role in preventing the need for root canal treatment or tooth extraction. Here, we developed an electrospun gelatin methacryloyl (GelMA) fibrous scaffold incorporating beta-tricalcium phosphate (TCP) particles for pulp capping. A comprehensive morphological, physical-chemical, and mechanical characterization of the engineered fibrous scaffolds was performed. In vitro bioactivity, cell compatibility, and odontogenic differentiation potential of the scaffolds in dental pulp stem cells (DPSCs) were also evaluated. A pre-clinical in vivo model was used to determine the therapeutic role of the GelMA/TCP scaffolds in promoting hard tissue formation. Morphological, chemical, and thermal analyses confirmed effective TCP incorporation in the GelMA nanofibers. The GelMA+20%TCP nanofibrous scaffold exhibited bead-free morphology and suitable mechanical and degradation properties. In vitro, GelMA+20%TCP scaffolds supported apatite-like formation, improved cell spreading, and increased deposition of mineralization nodules. Gene expression analysis revealed upregulation of ALPL, RUNX2, COL1A1, and DMP1 in the presence of TCP-laden scaffolds. In vivo, analyses showed mild inflammatory reaction upon scaffolds' contact while supporting mineralized tissue formation. Although the levels of Nestin and DMP1 proteins did not exceed those associated with the clinical reference treatment (i.e., mineral trioxide aggregate), the GelMA+20%TCP scaffold exhibited comparable levels, thus suggesting the emergence of differentiated odontoblast-like cells capable of dentin matrix secretion. Our innovative GelMA/TCP scaffold represents a simplified and efficient alternative to conventional pulp-capping biomaterials. STATEMENT OF SIGNIFICANCE: Vital pulp therapy (VPT) aims to preserve dental pulp vitality and avoid root canal treatment. Biomaterials that bolster mineralized tissue regeneration with ease of use are still lacking. We successfully engineered gelatin methacryloyl (GelMA) electrospun scaffolds incorporated with beta-tricalcium phosphate (TCP) for VPT. Notably, electrospun GelMA-based scaffolds containing 20% (w/v) of TCP exhibited favorable mechanical properties and degradation, cytocompatibility, and mineralization potential indicated by apatite-like structures in vitro and mineralized tissue deposition in vivo, although not surpassing those associated with the standard of care. Collectively, our innovative GelMA/TCP scaffold represents a simplified alternative to conventional pulp capping materials such as MTA and Biodentine™ since it is a ready-to-use biomaterial, requires no setting time, and is therapeutically effective.
Topics: Tissue Scaffolds; Cells, Cultured; Biocompatible Materials; Cell Differentiation; Apatites; Dental Pulp
PubMed: 37939819
DOI: 10.1016/j.actbio.2023.11.005 -
Advanced Healthcare Materials Sep 2023Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries-induced dental pulp infections. However, bacterial contamination...
Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries-induced dental pulp infections. However, bacterial contamination negatively affects dentine-pulp complex repair. The common capping materials show limited antimicrobial effects against some microorganisms. To improve the VPT efficacy, capping materials with increased antibacterial properties and enhanced odontogenic and angiogenic activities are needed. Herein, a SrCuSi O /gelatin methacrylate(SC/Gel) composite hydrogel has been proposed for infected dental pulp treatment. SrCuSi O (SC) is a microscale bioceramic composed of assembled multilayered nanosheets that possesses good near-infrared photothermal conversion ability and multiple bioactivities due to sustained Sr , Cu , and SiO ion release. It is shown that the SC/Gel composite hydrogel efficiently eliminates Streptococcus mutans and Lactobacillus casei and inhibits biofilm formation under photothermal heating, while the ion extract from SC promotes odontogenesis of rat dental pulp stem cells and angiogenesis of human umbilical vein endothelial cells. The as-designed therapeutic effect of SC/Gel composite hydrogel-mediated VPT has been proven in a rat dental pulp infection model and yielded improved dentine-pulp complex repair compared with the commercially used iRoot® BP Plus. This study suggests that the SC/Gel composite hydrogel is a potential pulp-capping material with improved effects on dentine-pulp complex repair in infected pulp.
Topics: Humans; Rats; Animals; Dental Pulp; Hydrogels; Endothelial Cells; Regeneration; Anti-Bacterial Agents
PubMed: 37260366
DOI: 10.1002/adhm.202300546 -
Biomolecules Mar 2024Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not... (Review)
Review
Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.
Topics: Regenerative Endodontics; Exosomes; Dental Pulp; Regeneration; Regenerative Medicine
PubMed: 38540750
DOI: 10.3390/biom14030330 -
Journal of Dental Research Apr 2024The quest for finding a suitable scaffold system that supports cell survival and function and, ultimately, the regeneration of the pulp-dentin complex remains...
The quest for finding a suitable scaffold system that supports cell survival and function and, ultimately, the regeneration of the pulp-dentin complex remains challenging. Herein, we hypothesized that dental pulp stem cells (DPSCs) encapsulated in a collagen-based hydrogel with varying stiffness would regenerate functional dental pulp and dentin when concentrically injected into the tooth slices. Collagen hydrogels with concentrations of 3 mg/mL (Col3) and 10 mg/mL (Col10) were prepared, and their stiffness and microstructure were assessed using a rheometer and scanning electron microscopy, respectively. DPSCs were then encapsulated in the hydrogels, and their viability and differentiation capacity toward endothelial and odontogenic lineages were evaluated using live/dead assay and quantitative real-time polymerase chain reaction. For in vivo experiments, DPSC-encapsulated collagen hydrogels with different stiffness, with or without growth factors, were injected into pulp chambers of dentin tooth slices and implanted subcutaneously in severe combined immunodeficient (SCID) mice. Specifically, vascular endothelial growth factor (VEGF [50 ng/mL]) was loaded into Col3 and bone morphogenetic protein (BMP2 [50 ng/mL]) into Col10. Pulp-dentin regeneration was evaluated by histological and immunofluorescence staining. Data were analyzed using 1-way or 2-way analysis of variance accordingly (α = 0.05). Rheology and microscopy data revealed that Col10 had a stiffness of 8,142 Pa with a more condensed and less porous structure, whereas Col3 had a stiffness of 735 Pa with a loose microstructure. Furthermore, both Col3 and Col10 supported DPSCs' survival. Quantitative polymerase chain reaction showed Col3 promoted significantly higher von Willebrand factor (VWF) and CD31 expression after 7 and 14 d under endothelial differentiation conditions ( < 0.05), whereas Col10 enhanced the expression of dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and collagen 1 (Col1) after 7, 14, and 21 d of odontogenic differentiation ( < 0.05). Hematoxylin and eosin and immunofluorescence (CD31 and vWF) staining revealed Col10+Col3+DPSCs+GFs enhanced pulp-dentin tissue regeneration. In conclusion, the collagen-based concentric construct modified by growth factors guided the specific lineage differentiation of DPSCs and promoted pulp-dentin tissue regeneration in vivo.
Topics: Mice; Animals; Cells, Cultured; Vascular Endothelial Growth Factor A; von Willebrand Factor; Hydrogels; Mice, SCID; Collagen; Cell Differentiation; Intercellular Signaling Peptides and Proteins; Dentin; Dental Pulp; Cell Proliferation
PubMed: 38410924
DOI: 10.1177/00220345241226649 -
International Endodontic Journal Sep 2023Previous studies have evaluated the pulpal responses to calcium silicate cements (CSCs) on normal dental pulp, but investigations on the effects of CSCs on inflamed pulp...
AIM
Previous studies have evaluated the pulpal responses to calcium silicate cements (CSCs) on normal dental pulp, but investigations on the effects of CSCs on inflamed pulp are limited. This study aimed to test the inflammatory response and odontogenic differentiation of inflamed rat dental pulp after direct pulp capping with CSCs.
METHODOLOGY
Wistar rat molars pulps were exposed for 48 h to induce inflammation and then capped with ProRoot MTA (Dentsply), Biodentine (Septodont), RetroMTA (Bio MTA) and Dycal (Dentsply Caulk). The degree of pulpal inflammation and hard tissue formation was evaluated by histological analysis. Immunofluorescence staining for interleukin (IL)-6, osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2) was also performed.
RESULTS
After 4 weeks, complete recovery from inflammation was evident in 22%, 37.5%, 10% and none of the ProRoot MTA, Biodentine, RetroMTA and Dycal samples, respectively. Heavy hard tissue deposition as a continuous hard tissue bridge was observed in 77.8%, 75%, 70% and 60% of the ProRoot MTA, Biodentine, RetroMTA and Dycal samples, respectively. IL-6, OCN and RUNX2 were detected in all materials, mainly adjacent to areas of inflammation and reparative dentine formation. At one, two and 4 weeks, significant differences were not observed between the inflammation and hard tissue formation scores of the four material groups (p > .05).
CONCLUSIONS
In this study, pulpal inflammation was still present in most specimens at 4 weeks after pulp capping and a significant number of samples showed incomplete and discontinuous dentine bridge formation. The results of this study suggest that initial inflammatory conditions of the pulp may risk the prognosis of teeth treated with CSCs.
Topics: Animals; Rats; Aluminum Compounds; Calcium Compounds; Core Binding Factor Alpha 1 Subunit; Dental Pulp; Dental Pulp Capping; Drug Combinations; Inflammation; Osteocalcin; Oxides; Pulp Capping and Pulpectomy Agents; Rats, Wistar; Silicates
PubMed: 37350351
DOI: 10.1111/iej.13947 -
Stem Cell Reviews and Reports Nov 2023Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the...
BACKGROUND
Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the neuronal differentiation of dental pulp-derived stem cells (DPSC) remains inadequately explored. The current study aims to define the regulatory role of KLF2 (Kruppel-like factor 2) during the neural differentiation (ND) of DPSC.
METHODS
We first investigated the transcriptional and translational expression of KLF2, autophagy, and mitophagy-associated markers during the ND of DPSC by using quantitative RT-PCR and western blot methods. After that, we applied the chemical-mediated loss- and gain-of-function approaches using KLF2 inhibitor, GGPP (geranylgeranyl pyrophosphate), and KLF2 activator, GGTI-298 (geranylgeranyl transferase inhibitor-298) to delineate the role of KLF2 during ND of DPSC. The western blot, qRT-PCR, and immunocytochemistry were performed to determine the molecular changes during ND after KLF2 deficiency and KLF2 sufficiency. We also analyzed the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) using the Seahorse XFe24 analyzer.
RESULTS
Our study demonstrated that the expression level of KLF2, autophagy, and mitophagy-associated markers were significantly elevated during the ND of DPSC. Next, we found that the KLF2 inhibitor, GGPP significantly reduced the ND of DPSC. Inversely, KLF2 overexpression accelerated the molecular phenomenon of DPSC's commitment towards ND, indicating the crucial role of KLF2 in neurogenesis. Moreover, we found that the KLF2 positively regulated autophagy, mitophagy, and the Wnt5a signaling pathway during neurogenesis. Seahorse XFe24 analysis revealed that the ECAR and OCR parameters were significantly increased during ND, and inhibition of KLF2 marginally reversed them towards DPSC's cellular bioenergetics. However, KLF2 overexpression shifted the cellular energy metabolism toward the quiescent stage.
CONCLUSION
Collectively, our findings provide the first evidence that the KLF2 critically regulates the neurogenesis of DPSC by inducing autophagy and mitophagy.
Topics: Autophagy; Cell Differentiation; Dental Pulp; Mitophagy; Stem Cells; Transcription Factors; Humans
PubMed: 37642902
DOI: 10.1007/s12015-023-10607-0 -
ACS Nano Mar 2024Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to...
Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to direct tissue-specific regeneration. Therefore, it is necessary to optimize the osteogenic capacity of EV-based systems for repairing extensive bone defects. Herein, we show that hydrogels loaded with osteoinductive dental pulp stem cell-derived EVs (Ost-EVs) enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold increase in the expression of bone morphogenetic protein 2 (BMP2) compared to the hydrogel control group. Moreover, Ost-EVs led to a higher expression of alkaline phosphatase (ALP) (1.88 ± 0.16 of Ost-EVs relative to Nor-EVs) and the formation of orange-red calcium nodules (1.38 ± 0.10 of Ost-EVs relative to Nor-EVs) . RNA sequencing revealed that Ost-EVs showed significantly high miR-1246 expression. An ideal hydrogel implant should also adhere to surrounding moist tissues. In this study, we were drawn to mussel-inspired adhesive modification, where the hydrogel carrier was crafted from hyaluronic acid (HA) and polyethylene glycol derivatives, showcasing impressive tissue adhesion, self-healing capabilities, and the ability to promote bone growth. The modified HA (mHA) hydrogel was also responsive to environmental stimuli, making it an effective carrier for delivering EVs. In an ectopic osteogenesis animal model, the Ost-EV/hydrogel system effectively alleviated inflammation, accelerated revascularization, and promoted tissue mineralization. We further used a rat femoral condyle defect model to evaluate the osteogenic ability of the Ost-EVs/hydrogel system. Collectively, our results suggest that Ost-EVs combined with biomaterial-based hydrogels hold promising potential for treating bone defects.
Topics: Rats; Animals; Hydrogels; Dental Pulp; Cell Differentiation; Bone Regeneration; Osteogenesis; Stem Cells; Hyaluronic Acid; Extracellular Vesicles
PubMed: 38488479
DOI: 10.1021/acsnano.3c11542 -
Pediatric Dentistry Jan 2024The purpose of this study was to present an evidence-based guideline for primary teeth with deep caries or trauma requiring vital pulp therapies (VPT). A systematic... (Meta-Analysis)
Meta-Analysis
The purpose of this study was to present an evidence-based guideline for primary teeth with deep caries or trauma requiring vital pulp therapies (VPT). A systematic review/meta-analysis on vital primary teeth resulting from trauma or caries was conducted using GRADE to assess the certainty of evidence for clinical recommendations. A decision tree was provided for choosing VPTs. No articles on trauma VPT were found. For VPT in primary teeth with deep caries, indirect pulp treatment (IPT) or pulpotomy using the calcium silicate cement (mineral trioxide aggregate [MTA] or Biodentine) show increased success over using direct pulp capping (DPC) and other pulpotomies. Different liners do not affect IPT success (high certainty) or DPC capping agents' success (very low certainty) after 24 months. It is strongly recommended, with high certainty from 24-month data, that calcium silicate cement pulpotomy is preferred over formocresol, ferric sulfate, zinc oxide eugenol pulpotomy, and other pulpotomies. Using selective caries removal and IPT for deep caries is strongly recommended with moderate certainty over complete and stepwise removal. Statistically, this results in significantly fewer pulp exposures. No caries removal and Hall technique crown may be used when indicated (moderate certainty at 24 months). For vital primary incisors with deep caries, pulpotomy was significantly better statistically than pulpectomy. Teeth diagnosed with/without reversible pulpitis pain showed comparable success after 12 months of treatment by IPT or calcium silicate cement pulpotomy. The following had little or no significant effect on MTA pulpotomy success: coronal pulp removal methods; irrigation solution; method to control hemorrhage; base over MTA; treatment in one or two visits; anterior or posterior teeth. Indirect pulp treatment or calcium silicate cement pulpotomy is likely to increase vital pulp therapy success over other VPTs such as direct pulp capping and other pulpotomies after 24 months (moderate certainty).
Topics: Humans; Dental Care; Pulpotomy; Dental Pulp; Calcium; Dental Cements; Glass Ionomer Cements; Tooth, Deciduous; Calcium Compounds; Silicates
PubMed: 38449041
DOI: No ID Found -
Bioactive Materials Aug 2024Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental... (Review)
Review
Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.
PubMed: 38745589
DOI: 10.1016/j.bioactmat.2024.04.031 -
Advanced Materials (Deerfield Beach,... May 2024It remains an obstacle to induce the regeneration of hard dentin tissue in clinical settings. To overcome this, a P(VDF-TrFE) piezoelectric film with 2 wt% SrCl addition...
It remains an obstacle to induce the regeneration of hard dentin tissue in clinical settings. To overcome this, a P(VDF-TrFE) piezoelectric film with 2 wt% SrCl addition is designed. The biofilm shows a high flexibility, a harmonious biocompatibility, and a large piezoelectric d coefficient of 14 pC N, all contributing to building an electric microenvironment that favor the recruitment of dental pulp stem cells (DPSCs) and their differentiation into odontoblasts during normal chewing, speaking, etc. On the other hand, the strontium ions can be gradually released from the film, thus promoting DPSC odonto-differentiation. In vivo experiments also demonstrate that the film induces the release of dentin minerals and regeneration of dentin tissue. In the large animal dentin defect models, this piezoelectric film induces in situ dentin tissue formation effectively over a period of three months. This study illustrates a therapeutic potential of the piezoelectric film to improve dentin tissue repair in clinical settings.
Topics: Dentin; Biofilms; Dental Pulp; Strontium; Animals; Humans; Regeneration; Stem Cells; Cell Differentiation; Odontoblasts; Biocompatible Materials
PubMed: 38335452
DOI: 10.1002/adma.202313419