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9 "Regenerative endodontics"
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Review Article
Stem cell-derived exosomes for dentin-pulp complex regeneration: a mini-review
Dina A. Hammouda, Alaa M Mansour, Mahmoud A. Saeed, Ahmed R. Zaher, Mohammed E. Grawish
Restor Dent Endod 2023;48(2):e20.   Published online May 3, 2023
DOI: https://doi.org/10.5395/rde.2023.48.e20
AbstractAbstract PDFPubReaderePub

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.

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Research Articles
Comparative analysis of bond strength to root dentin and compression of bioceramic cements used in regenerative endodontic procedures
Maykely Naara Morais Rodrigues, Kely Firmino Bruno, Ana Helena Gonçalves de Alencar, Julyana Dumas Santos Silva, Patrícia Correia de Siqueira, Daniel de Almeida Decurcio, Carlos Estrela
Restor Dent Endod 2021;46(4):e59.   Published online November 9, 2021
DOI: https://doi.org/10.5395/rde.2021.46.e59
AbstractAbstract PDFPubReaderePub
Objectives

This study compared the Biodentine, MTA Repair HP, and Bio-C Repair bioceramics in terms of bond strength to dentin, failure mode, and compression.

Materials and Methods

Fifty-four slices obtained from the cervical third of 18 single-rooted human mandibular premolars were randomly distributed (n = 18). After insertion of the bioceramic materials, the push-out test was performed. The failure mode was analyzed using stereomicroscopy. Another set of cylindrically-shaped bioceramic samples (n = 10) was prepared for compressive strength testing. The normality of data distribution was analyzed using the Shapiro-Wilk test. The Kruskal-Wallis and Friedman tests were used for the push-out test data, while compressive strength was analyzed with analysis of variance and the Tukey test, considering a significance level of 0.05.

Results

Biodentine presented a higher median bond strength value (14.79 MPa) than MTA Repair HP (8.84 MPa) and Bio-C Repair (3.48 MPa), with a significant difference only between Biodentine and Bio-C Repair. In the Biodentine group, the most frequent failure mode was mixed (61%), while in the MTA Repair HP and Bio-C Repair groups, it was adhesive (94% and 72%, respectively). Biodentine showed greater resistance to compression (29.59 ± 8.47 MPa) than MTA Repair HP (18.68 ± 7.40 MPa) and Bio-C Repair (19.96 ± 3.96 MPa) (p < 0.05).

Conclusions

Biodentine showed greater compressive strength than MTA Repair HP and Bio-C Repair, and greater bond strength than Bio-C Repair. The most frequent failure mode of Biodentine was mixed, while that of MTA Repair HP and Bio-C Repair was adhesive.

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A novel antimicrobial-containing nanocellulose scaffold for regenerative endodontics
Victoria Kichler, Lucas Soares Teixeira, Maick Meneguzzo Prado, Guilherme Colla, Daniela Peressoni Vieira Schuldt, Beatriz Serrato Coelho, Luismar Marques Porto, Josiane de Almeida
Restor Dent Endod 2021;46(2):e20.   Published online March 16, 2021
DOI: https://doi.org/10.5395/rde.2021.46.e20
AbstractAbstract PDFPubReaderePub
Objectives

The aim of this study was to evaluate bacterial nanocellulose (BNC) membranes incorporated with antimicrobial agents regarding cytotoxicity in fibroblasts of the periodontal ligament (PDLF), antimicrobial activity, and inhibition of multispecies biofilm formation.

Materials and Methods

The tested BNC membranes were BNC + 1% clindamycin (BNC/CLI); BNC + 0.12% chlorhexidine (BNC/CHX); BNC + nitric oxide (BNC/NO); and conventional BNC (BNC; control). After PDLF culture, the BNC membranes were positioned in the wells and maintained for 24 hours. Cell viability was then evaluated using the MTS calorimetric test. Antimicrobial activity against Enterococcus faecalis, Actinomyces naeslundii, and Streptococcus sanguinis (S. sanguinis) was evaluated using the agar diffusion test. To assess the antibiofilm activity, BNC membranes were exposed for 24 hours to the mixed culture. After sonicating the BNC membranes to remove the remaining biofilm and plating the suspension on agar, the number of colony-forming units (CFU)/mL was determined. Data were analyzed by 1-way analysis of variance and the Tukey, Kruskal-Wallis, and Dunn tests (α = 5%).

Results

PDLF metabolic activity after contact with BNC/CHX, BNC/CLI, and BNC/NO was 35%, 61% and 97%, respectively, compared to BNC. BNC/NO showed biocompatibility similar to that of BNC (p = 0.78). BNC/CLI showed the largest inhibition halos, and was superior to the other BNC membranes against S. sanguinis (p < 0.05). The experimental BNC membranes inhibited biofilm formation, with about a 3-fold log CFU reduction compared to BNC (p < 0.05).

Conclusions

BNC/NO showed excellent biocompatibility and inhibited multispecies biofilm formation, similarly to BNC/CLI and BNC/CHX.

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Case Reports
Pulp revascularization with and without platelet-rich plasma in two anterior teeth with horizontal radicular fractures: a case report
Edison Arango-Gómez, Javier Laureano Nino-Barrera, Gustavo Nino, Freddy Jordan, Henry Sossa-Rojas
Restor Dent Endod 2019;44(4):e35.   Published online August 20, 2019
DOI: https://doi.org/10.5395/rde.2019.44.e35
AbstractAbstract PDFPubReaderePub

Pulp revascularization is an alternative treatment in immature traumatized teeth with necrotic pulp. However, this procedure has not been reported in horizontal root fractures. This is a case report of a 9-year-old patient with multiple horizontal root fractures in 2 upper central incisors that were successfully treated with pulp revascularization. The patient presented for treatment 2 years after the initial trauma, and revascularization was attempted after the initial treatment with calcium hydroxide had failed. Prior to pulp revascularization, cone-beam computed tomography and autoradiograms demonstrated multiple horizontal fractures in the middle and apical thirds of the roots of the 2 affected teeth. Revascularization was performed in both teeth; platelet-rich plasma (PRP) was used in one tooth (#11) and the conventional method (blood clot) was used in the other tooth (#21). Clinical and radiographic follow-up over 4 years demonstrated pulp calcification in the PRP-treated tooth. Neither of the 2 teeth were lost, and the root canal calcification of tooth #11 was greater than that of tooth #21. This case suggests that PRP-based pulp revascularization may be an alternative for horizontal root fractures.

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Retreatment of failed regenerative endodontic of orthodontically treated immature permanent maxillary central incisor: a case report
Musaed Fahad Al-Tammami, Saad A. Al-Nazhan
Restor Dent Endod 2017;42(1):65-71.   Published online October 28, 2016
DOI: https://doi.org/10.5395/rde.2017.42.1.65
AbstractAbstract PDFPubReaderePub

A revascularization procedure was shown to be the best alternative therapy for immature teeth with necrotic pulp and apical infection. A 12 year old female with a history of trauma to her upper central incisor and a sinus tract was referred for endodontic treatment. She was an active orthodontic patient and had undergone regenerative endodontic treatment for the past 2 years. Clinical examination revealed no response to sensibility, percussion, and palpation tests. The preoperative radiograph showed an open apex and apical rarefaction. The case was diagnosed as previously treated tooth with asymptomatic apical periodontitis. Regenerative endodontic retreatment was performed, and the case was followed for 3 years. Clinical, radiographic, and cone-beam computed tomography follow-up examination revealed an asymptomatic tooth, with evidence of periapical healing and root maturation.

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Research Articles
Biocompatibility of two experimental scaffolds for regenerative endodontics
Dephne Jack Xin Leong, Frank C. Setzer, Martin Trope, Bekir Karabucak
Restor Dent Endod 2016;41(2):98-105.   Published online March 28, 2016
DOI: https://doi.org/10.5395/rde.2016.41.2.98
AbstractAbstract PDFPubReaderePub
Objectives

The biocompatibility of two experimental scaffolds for potential use in revascularization or pulp regeneration was evaluated.

Materials and Methods

One resilient lyophilized collagen scaffold (COLL), releasing metronidazole and clindamycin, was compared to an experimental injectable poly(lactic-co-glycolic) acid scaffold (PLGA), releasing clindamycin. Human dental pulp stem cells (hDPSCs) were seeded at densities of 1.0 × 104, 2.5 × 104, and 5.0 × 104. The cells were investigated by light microscopy (cell morphology), MTT assay (cell proliferation) and a cytokine (IL-8) ELISA test (biocompatibility).

Results

Under microscope, the morphology of cells coincubated for 7 days with the scaffolds appeared healthy with COLL. Cells in contact with PLGA showed signs of degeneration and apoptosis. MTT assay showed that at 5.0 × 104 hDPSCs, COLL demonstrated significantly higher cell proliferation rates than cells in media only (control, p < 0.01) or cells co-incubated with PLGA (p < 0.01). In ELISA test, no significant differences were observed between cells with media only and COLL at 1, 3, and 6 days. Cells incubated with PLGA expressed significantly higher IL-8 than the control at all time points (p < 0.01) and compared to COLL after 1 and 3 days (p < 0.01).

Conclusions

The COLL showed superior biocompatibility and thus may be suitable for endodontic regeneration purposes.

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Effect of dentin treatment on proliferation and differentiation of human dental pulp stem cells
Minjeong Park, Nan-Sim Pang, Il-Young Jung
Restor Dent Endod 2015;40(4):290-298.   Published online September 23, 2015
DOI: https://doi.org/10.5395/rde.2015.40.4.290
AbstractAbstract PDFPubReaderePub
Objectives

Sodium hypochlorite (NaOCl) is an excellent bactericidal agent, but it is detrimental to stem cell survival, whereas intracanal medicaments such as calcium hydroxide (Ca[OH]2) promote the survival and proliferation of stem cells. This study evaluated the effect of sequential NaOCl and Ca[OH]2 application on the attachment and differentiation of dental pulp stem cells (DPSCs).

Materials and Methods

DPSCs were obtained from human third molars. All dentin specimens were treated with 5.25% NaOCl for 30 min. DPSCs were seeded on the dentin specimens and processed with additional 1 mg/mL Ca[OH]2, 17% ethylenediaminetetraacetic acid (EDTA) treatment, file instrumentation, or a combination of these methods. After 7 day of culture, we examined DPSC morphology using scanning electron microscopy and determined the cell survival rate with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We measured cell adhesion gene expression levels after 4 day of culture and odontogenic differentiation gene expression levels after 4 wk using quantitative real-time polymerase chain reaction.

Results

DPSCs did not attach to the dentin in the NaOCl-treated group. The gene expression levels of fibronectin-1 and secreted phosphoprotein-1 gene in both the Ca[OH]2- and the EDTA-treated groups were significantly higher than those in the other groups. All Ca[OH]2-treated groups showed higher expression levels of dentin matrix protein-1 than that of the control. The dentin sialophosphoprotein level was significantly higher in the groups treated with both Ca[OH]2 and EDTA.

Conclusions

The application of Ca[OH]2 and additional treatment such as EDTA or instrumentation promoted the attachment and differentiation of DPSCs after NaOCl treatment.

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Review Article
Platelet rich fibrin - a novel acumen into regenerative endodontic therapy
Kavita Hotwani, Krishna Sharma
Restor Dent Endod 2014;39(1):1-6.   Published online January 20, 2014
DOI: https://doi.org/10.5395/rde.2014.39.1.1
AbstractAbstract PDFPubReaderePub

Research into regenerative dentistry has added impetus onto the field of molecular biology. It can be documented as a prototype shift in the therapeutic armamentarium for dental disease. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. A new family of platelet concentrates called the platelet rich fibrin (PRF) has been recently used by several investigators and has shown application in diverse disciplines of dentistry. This paper is intended to add light on the various prospects of PRF and clinical insights to regenerative endodontic therapy.

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Case Report
Prevention of tooth discoloration associated with triple antibiotics
Bona Kim, Min-Ju Song, Su-Jung Shin, Jeong-Won Park
Restor Dent Endod 2012;37(2):119-122.   Published online May 18, 2012
DOI: https://doi.org/10.5395/rde.2012.37.2.119
AbstractAbstract PDFPubReaderePub

Regenerative endodontics has a potential to heal a partially necrotic pulp, which can be beneficial for the continued root development and strengthening of immature teeth. For this purpose, triple antibiotic mixture of ciprofloxacin, metronidazole, and minocycline was recommended as intracanal medicament in an attempt to disinfect the root canal system for revascularization of a tooth with a necrotic pulp. However, discoloration of the tooth was reported after applying this. This case shows the idea for preventing the tooth discoloration using a delivery syringe (SW-O-01, Shinwoo dental) to avoid the contact between the clinical crown and the antibiotics.

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