Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.

UNASSIGNED: The present systematic review aims to assess the success rate of the pulp regeneration treatment, according to the American Association of Endodontists (AAE) criteria, using different bioactive materials in permanent teeth of pediatric subjects (6-17 years of age).
UNASSIGNED: The study protocol was registered on PROSPERO and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The question formulation was accomplished using the PICO model, and an electronic search was carried out on Scopus, MEDLINE/PubMed, Web of Science, and Cochrane databases till April 1, 2023. A total of 30 studies were established to fulfill the inclusion criteria of this systematic review.
UNASSIGNED: A total of 273 teeth have been treated with pulp regeneration treatment. By comparing different biomaterials and the success criteria defined by the AAE, the material associated with a higher success rate was found to be the white mineral trioxide aggregate. However, the overall success rate of pulp regeneration treatment was reported for 248 out of 273 teeth (91.20%).
UNASSIGNED: Data obtained support the potential that regenerative endodontics aids in continuing root development in permanent immature teeth. Further studies are needed for a more extensive evaluation of the use of different biomaterials and the success rate in regenerative endodontics.

This case report details a pulp revascularization treatment administered to a mature permanent tooth exhibiting pulp necrosis. A 22-years old female patient complained of the recurrence of a sinus tract labial of the maxillary right central incisor; which was tender on biting. Diagnosis of pulp necrosis and symptomatic apical periodontitis. Preoperative periapical and CBCT radiographs showed root with wide apical foramen and large apical radiolucency. Pulp revascularization procedure was performed using 1.3% sodium hypochlorite irrigation, 17% Ethylenediaminetetraacetic acid irrigation, and calcium hydroxide intracanal dressing for 2 weeks. During the last visit, intentional bleeding was induced, collagen matrix was set over the blood clot, 2 mm of mineral trioxide aggregate and glass-ionomer filling was placed. A year of follow-up, the tooth showed no signs or symptoms and responded normally to the sensibility tests. Intra-oral periapical radiograph and the CBCT showed significant reduction in the periapical lesion\'s size, slight reduction in the apical foramen\'s size, and hard radiopaque material deposition at the root\'s middle third.

UNASSIGNED: Dental tissue engineering is an alternative procedure for restoring damaged dental tissues. Adipose-derived stem cells are a new source of cells for regenerative endodontics in combination with scaffold materials. The descriptive data about this regenerative process is still insufficient.
UNASSIGNED: To evaluate the regenerative potential of Adipose-derived stem cells using a self-assembling polypeptide scaffold for the dentin-pulp complex in an emptied root canal space.
UNASSIGNED: 40 root segments of human single-rooted teeth were transplanted into the albino rats\' dorsal subcutaneous tissue. Root segments were divided into two groups: group I contained only a self-assembling polypeptide scaffold, and group II contained fluorescent-labeled Adipose-derived stem cells embedded in a self-assembling polypeptide scaffold. The newly formed tissues were assessed on the 60th and 90th days post-transplantation using routine histological examination, Masson trichrome staining, and scanning electron microscopy.
UNASSIGNED: Group I showed granulation tissue without any signs of predentin formation or odontoblast-like cells. Group II revealed the presence of predentin tissue along the dentin margin, with arranged odontoblast-like cells. An organized connective tissue with abundant vasculature and calcific masses was observed in the pulp space.
UNASSIGNED: Adipose-derived stem cells can be considered as alternative stem cells for regenerating the dentin-pulp complex. Dentin pulp complex regeneration utilizing a self-assembling polypeptide scaffold alone would not yield successful results.

Regenerative endodontic therapy is a promising approach to restore the vitality of necrotic teeth, however, pulp regeneration in mature permanent teeth remains a substantial challenge due to insufficient developmental signals. The dentin is embryologically and histologically similar to the pulp, which contains a cocktail of pulp-specific structural proteins and growth factors, thus we proposed an optimizing strategy to obtain dentin matrix extracted proteins (DMEP) and engineered a DMEP functionalized double network hydrogel, whose physicochemical property was tunable by adjusting polymer concentrations to synchronize with regenerated tissues. In vitro models showed that the biomimetic hydrogel with sustained release of DMEP provided a beneficial microenvironment for the encapsulation, propagation and migration of human dental pulp stem cells (hDPSCs). The odontogenic and angiogenic differentiation of hDPSCs were enhanced as well. To elicit the mechanism hidden in the microenvironment to guide cell fate, RNA sequencing was performed and 109 differential expression of genes were identified, the majority of which enriched in cell metabolism, cell differentiation and intercellular communications. The involvement of ERK, p38 and JNK MAPK signaling pathways in the process was confirmed. Of note, in vivo models showed that the injectable and in situ photo-crosslinkable hydrogel was user-friendly for root canal systems and was capable of inducing the regeneration of highly organized and vascularized pulp-like tissues in root segments that subcutaneously implanted into nude mice. Taken together, this study reported a facile and efficient way to fabricate a cell delivery hydrogel with pulp-specific developmental cues, which exhibited promising application and translation potential in future regenerative endodontic fields.

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM\'s in situ transplantation for regenerative endodontics.

BACKGROUND: Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration.
RESULTS: We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1).
CONCLUSIONS: The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.

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.

BACKGROUND: Decellularized extracellular matrix (dECM) from several tissue sources has been proposed as a promising alternative to conventional scaffolds used in regenerative endodontic procedures (REPs). This systematic review aimed to evaluate the histological outcomes of studies utilizing dECM-derived scaffolds for REPs and to analyse the contributing factors that might influence the nature of regenerated tissues.
METHODS: The PRISMA 2020 guidelines were used. A search of articles published until April 2024 was conducted in Google Scholar, Scopus, PubMed and Web of Science databases. Additional records were manually searched in major endodontic journals. Original articles including histological results of dECM in REPs and in-vivo studies were included while reviews, in-vitro studies and clinical trials were excluded. The quality assessment of the included studies was analysed using the ARRIVE guidelines. Risk of Bias assessment was done using the (SYRCLE) risk of bias tool.
RESULTS: Out of the 387 studies obtained, 17 studies were included for analysis. In most studies, when used as scaffolds with or without exogenous cells, dECM showed the potential to enhance angiogenesis, dentinogenesis and to regenerate pulp-like and dentin-like tissues. However, the included studies showed heterogeneity of decellularization methods, animal models, scaffold source, form and delivery, as well as high risk of bias and average quality of evidence.
CONCLUSIONS: Decellularized ECM-derived scaffolds could offer a potential off-the-shelf scaffold for dentin-pulp regeneration in REPs. However, due to the methodological heterogeneity and the average quality of the studies included in this review, the overall effectiveness of decellularized ECM-derived scaffolds is still unclear. More standardized preclinical research is needed as well as well-constructed clinical trials to prove the efficacy of these scaffolds for clinical translation.
UNASSIGNED: The protocol was registered in PROSPERO database #CRD42023433026. This review was funded by the Science, Technology and Innovation Funding Authority (STDF) under grant number (44426).

UNASSIGNED: The aim of the current study is to evaluate the effect of calcium phophosilicate-based bioceramic \"Totalfill bioceramic putty\" and white mineral trioxide aggregate (WMTA) as the coronal plug on discoloration after revascularization of necrotic immature permanent anterior teeth.
UNASSIGNED: This study was conducted on (48) necrotic young permanent central incisors in children ranging from 8 to 14 years old, that were randomly allocated to either Totalfill bioceramic (Group I = 24) or WMTA (Group II = 24) as the coronal plug. Two visits revascularization protocol was adopted in this study using 1.5% sodium hypochlorite, followed by 17% ethylenediaminetetraacetic acid, and ending with a saline flush as irrigation solution. The double antibiotic paste was used as intracanal medication. The blood clot was used as scaffold followed by the application of collagen membrane followed by coronal plud malterial. Finally, the access was sealed using resin composite restoration and composite restoration. Clinical assessment was conducted at 1, 3, 6, 9, and 12 months, while radiographic assessment was conducted at 6 and 12 months. Data were statistically analyzed using the Chi-squared test for intergroup comparisons and Cochran\'s Q test for intragroup comparison.
UNASSIGNED: Clinically, Group I exhibited a success rate of 100%, whereas Group II exhibited a success rate of 85.7%. Radiographically, both materials showed a 90.5% success rate. There was no statistically significant difference between both materials for all assessed clinical and radiographic parameters at different follow-up periods.
UNASSIGNED: Both Totalfill bioceramic putty and WMTA can be used successfully as coronal plug in esthetic areas.