• Restorative Dentistry and Endodontics
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• v.48 no.2
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• pp.20.1-20.13
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• 2023

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

• Restorative Dentistry and Endodontics
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• v.44 no.2
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• pp.20.1-20.8
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• 2019

Objectives: To achieve pulp-dentin complex regeneration with tissue engineering, treatment efficacies and safeties should be evaluated using in vivo orthotopic transplantation in a sufficient number of animals. Mice have been a species of choice in which to study stem cell biology in mammals. However, most pulp-dentin complex regeneration studies have used large animals because the mouse tooth is too small. The purpose of this study was to demonstrate the utility of the mouse tooth as a transplantation model for pulp-dentin complex regeneration research. Materials and Methods: Experiments were performed using 7-week-old male Institute of Cancer Research (ICR) mice; a total of 35 mice had their pulp exposed, and 5 mice each were sacrificed at 1, 2, 4, 7, 9, 12 and 14 days after pulp exposure. After decalcification in 5% ethylenediaminetetraacetic acid, the samples were embedded and cut with a microtome and then stained with hematoxylin and eosin. Slides were observed under a high-magnification light microscope. Results: Until 1 week postoperatively, the tissue below the pulp chamber orifice appeared normal. The remaining coronal portion of the pulp tissue was inflammatory and necrotic. After 1 week postoperatively, inflammation and necrosis were apparent in the root canals inferior to the orifices. The specimens obtained after experimental day 14 showed necrosis of all tissue in the root canals. Conclusions: This study could provide opportunities for researchers performing in vivo orthotopic transplantation experiments with mice.

• Restorative Dentistry and Endodontics
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• v.35 no.4
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• pp.238-245
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• 2010

Numerous cases about additional growth of roots or pulp tissue regeneration by using various intracanal medicaments in immature permanent teeth with periapical or pulpal disease have been reported. The underlying mechanism has not been clearly delineated, but it has been widely accepted that undifferentiated mesenchymal cells and stem cells are involved. Moreover, the growth and deposition of osteoid or cementoid tissues have been observed in regenerated pulp and roots. This new and non-invasive treatment has brightened the future of endodontics, and enlarged the vision of regenerative root canal treatment with multi-potent stem cells and various tissue engineering techniques.

• Restorative Dentistry and Endodontics
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• v.29 no.4
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• pp.370-377
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• 2004

The purpose of this study was to regenerate human dental pulp tissues similar to native pulp tissues. Using the mixture of type I collagen solution, primary cells collected from the different tissues (pulp, gingiva, and skin) and NIH 3T3 ($1{\;}{\times}{\;}10^5{\;}cells/ml/well$) were cultured at 12-well plate at $37^{\circ}C$ for 14 days. Standardized photographs were taken with digital camera during 14 days and the diameter of the contracted collagen gel matrix was measured and statistically analyzed with student t-test. As one of the pulp tissue engineering, normal human dental pulp tissue and collagen gel matrix cultured with dental pulp cells for 14 days were fixed and stained with Hematoxyline & Eosin. According to this study, the results were as follows: 1. The contraction of collagen gel matrix cultured with pulp cells for 14 days was significantly higher than other fibroblasts (gingiva, skin) (p < 0.05), 2. The diameter of collagen gel matrix cultured with pulp cells was reduced to 70.4% after 7 days, and 57.1% after 14 days. 3. The collagen gel without any cells did not contract, whereas the collagen gel cultured with gingiva and skin showed mild contraction after 14 days (88.1% and 87.6% respectively). 4. The contraction of the collagen gel cultured with NIH 3T3 cells after 14 days was higher than those cultured with gingival and skin fibroblasts, but it was not statistically significant (72.1%, p > 0.05). 5. The collagen gel matrix cultured with pulp cells for 14 days showed similar shape with native pulp tissue without blood vessels. This approach may provide a means of engineering a variety of other oral tissue as well and these cell behaviors may provide information needed to establish pulp tissue engineering protocols.

• International Journal of Oral Biology
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• v.46 no.2
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• pp.67-73
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• 2021

This study summarizes the recent cutting-edge approaches for dentin regeneration that still do not offer adequate solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.

• Development and Reproduction
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• v.17 no.3
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• pp.215-220
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• 2013

Recently, the RNA/DNA-binding protein FUS, Fused in sarcoma, was shown to play a role in growth, differentiation, and morphogenesis in vertebrates. Because little is known about Fus, we investigated its expression pattern in murine tooth development. In situ hybridization of mouse mandibles at specific developmental stages was performed with a DIG-labeled RNA probe. During early tooth development, Fus was detected in the dental epithelium and dental mesenchyme at 11 days postcoitum (dpc) and 12 dpc. From 14 dpc, Fus was strongly expressed in the dental papilla and the cervical loop of the dental epithelium. At postnatal day 4 (PN4), Fus expression was observed in the odontoblasts, ameloblasts, the proliferation zone of the pulp, and the cervical loop. At PN14, the expression pattern of Fus was found to be maintained in the odontoblasts and the proliferation zone of the pulp. Furthermore, Fus expression was especially strong in the Hertwig's epithelial root sheath (HERS). Therefore, this study suggests that Fus may play a role in the HERS during root development.

• Journal of Periodontal and Implant Science
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• v.43 no.6
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• pp.315-322
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• 2013

Purpose: In this study, we investigated the effect of silk scaffolds on one-wall periodontal intrabony defects. We conjugated nano-hydroxyapatite (nHA) onto a silk scaffold and then seeded periodontal ligament cells (PDLCs) or dental pulp cells (DPCs) onto the scaffold. Methods: Five dogs were used in this study. Bilateral 4 mm${\times}$2 mm (depth${\times}$mesiodistal width), one-wall intrabony periodontal defects were surgically created on the distal side of the mandibular second premolar and the mesial side of the mandibular fourth premolar. In each dog, four of the defects were separately and randomly assigned to the following groups: the PDLCcultured scaffold transplantation group (PDLC group), the DPC-cultured scaffold transplantation group (DPC group), the normal saline-soaked scaffold transplantation group, and the control group. The animals were euthanized following an 8-week healing interval for clinical, scanning electron microscopy (SEM), and histologic evaluations. Results: There was no sign of inflammation or other clinical signs of postoperative complications. The examination of cellseeded constructs by SEM provided visual confirmation of the favorable characteristics of nHA-coated silk scaffolds for tissue engineering. The scaffolds exhibited a firm connective porous structure in cross section, and after PDLCs and DPCs were seeded onto the scaffolds and cultured for 3 weeks, the attachment of well-spread cells and the formation of extracellular matrix (ECM) were observed. The histologic analysis revealed that a well-maintained grafted volume was present at all experimental sites for 8 weeks. Small amounts of inflammatory cells were seen within the scaffolds. The PDLC and DPC groups did not have remarkably different histologic appearances. Conclusions: These observations indicate that nHA-coated silk scaffolds can be considered to be potentially useful biomaterials for periodontal regeneration.

• The Journal of the Korean dental association
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• v.55 no.5
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• pp.352-357
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• 2017

Teeth are made up of three hard tissues, enamel, dentin, and cementum. The dental pulp is the only non-mineralized connective tooth tissue that is surrounded by dentin. The dentin-pulp complex is able to respond to injury by producing hard tissue deposition. However, dentin is considered one of the most difficult tissues to regenerate because of its unique anatomic and physiologic nature. Recently, advances in understanding the applicability of bio-active dentin regenerating proteins are emerging with the development of biological-based therapies using bio-active materials. Dentin defects were regenerated by the deposition of tubular physiologic dentin after application of the bio-active protein in a beagle dog model. Therefore, the bio-active protein may be able to serve as a novel dentin regenerating material and improve symptoms of dentin hypersensitivity.

• International Journal of Oral Biology
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• v.47 no.4
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• pp.55-62
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• 2022

Bioactive flavonoids have been shown to improve the biological activity of stem cells derived from different sources in tissue regeneration. The goal of this study was to see how naringin, a natural flavonoid discovered in citrus fruits, affected the biological properties of human dental pulp stem cells (HDPSCs). In this study, we found that naringin increases the migratory ability of HDPSCs. Naringin increased matrix metalloproteinase-2 (MMP-2) and C-X-C chemokine receptor type 4 (CXCR4) mRNA and protein expression in HDPSCs. ARP100, a selective MMP-2 inhibitor, and AMD3100, a CXCR4 antagonist, both inhibited the naringin-induced migration of HDPSCs. Furthermore, naringin increased osteogenic differentiation of HDPSCs and the expression of the osteogenic-related marker, alkaline phosphatase in HDPSCs. Taken together, our findings suggest that naringin may be beneficial on dental tissue or bone regeneration by increasing the biological activities of HDPSCs.

• Restorative Dentistry and Endodontics
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• v.40 no.3
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• pp.179-187
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• 2015

Traditionally, apexification has been used to treat immature permanent teeth that have lost pulp vitality. This technique promotes the formation of an apical barrier to close the open apex so that the filling materials can be confined to the root canal. Because tissue regeneration cannot be achieved with apexification, a new technique called regenerative endodontic treatment was presented recently to treat immature permanent teeth. Regenerative endodontic treatment is a treatment procedure designed to replace damaged pulp tissue with viable tissue which restores the normal function of the pulp-dentin structure. After regenerative endodontic treatment, continued root development and hard tissue deposition on the dentinal wall can occur under ideal circumstances. However, it is difficult to predict the result of regenerative endodontic treatment. Therefore, the purpose of this study was to summarize multiple factors effects on the result of regenerative endodontic treatment in order to achieve more predictable results. In this study, we investigated the features of regenerative endodontic treatment in comparison with those of other pulp treatment procedures and analyzed the factors that have an effect on regenerative endodontic treatment.