A carbon dot nanozyme hydrogel enhances pulp regeneration activity by regulating oxidative stress in dental pulpitis.

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.

Research progress of dental pulp regeneration treatment. / å†ç”Ÿæ€§ç‰™é«“æ²»ç–—çš„ç ”ç©¶è¿›å±•.

The dental pulp is the only soft tissue structure within the tooth, serving functions such as sensation and nutrition. However, the dental pulp is highly susceptible to necrosis due to external factors. Currently, root canal therapy is the most commonly used treatment for pulp necrosis. Nevertheless, teeth treated with root canal therapy are prone to secondary infections and adverse outcomes like vertical root fractures. Regenerative endodontic therapy has emerged as a solution, aiming to replace damaged tooth structures, including dentin, root structure, and the pulp-dentin complex cells. This approach demonstrates significant advantages in addressing clinical symptoms and achieving regeneration of the root and even the pulp. Since the discovery of dental pulp stem cells, regenerative endodontic therapy has gained new momentum. Advances in cell transplantation and cell homing techniques have rapidly developed, showing promising potential for clinical applications.

Mapping global research in dental pulp regeneration: A 10-year bibliometric analysis.

Background: Dental pulp regeneration aims to restore the function and vitality of the dental pulp, which is the soft tissue inside the tooth. Research in this field is effective in trying to improve clinical practices and procedures. This study aimed to analyze the literature related to dental pulp regeneration and to create a documented research perspective for this field. Materials and Methods: This bibliometric study analyzes the research outputs of the subject area of dental pulp regeneration indexed in the Web of Science database between 2013 and 2023. SciMAT software was used to visualize and predict the trends in research on the topic. Results: In general, it has been observed that the stem cell cluster consistently had the highest number of articles across all periods. As we progressed through time, the significance of this cluster continued to grow, eventually becoming a crucial component in the motor theme during the last period. In addition, a significant portion of the studies conducted during different periods focused on identifying suitable materials for scaffold formation. Various materials, including polymers and bioactive glasses, were proposed as viable options for scaffold formation in different periods. Conclusion: Dental pulp stem cells (DPSCs), scaffold networks, growth factors, and regulatory factors are the three main factors that influence dental pulp regeneration. By analyzing maps and thematic clusters in dental pulp regeneration research, as well as considering indicators such as repetition frequency, centrality, and citation of these clusters, researchers can identify the strengths, weaknesses, and gaps in current research.

Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration.

Successful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three-dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp-dentin complex formation. In vivo studies show that short-term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary-like structures, and improves cell survival. Long-term transplantation further confirms its capability to promote the formation of pulp-like tissues rich in blood vessels and peripheral nerve-like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.

Heparin-Functionalized Bioactive Glass to Harvest Endogenous Growth Factors for Pulp Regeneration.

Pulp and periapical diseases can lead to the cessation of tooth development, resulting in compromised tooth structure and functions. Despite numerous efforts to induce pulp regeneration, effective strategies are still lacking. Growth factors (GFs) hold considerable promise in pulp regeneration due to their diverse cellular regulatory properties. However, the limited half-lives and susceptibility to degradation of exogenous GFs necessitate the administration of supra-physiological doses, leading to undesirable side effects. In this research, a heparin-functionalized bioactive glass (CaO-P2O5-SiO2-Heparin, abbreviated as PSC-Heparin) with strong bioactivity and a stable neutral pH is developed as a promising candidate to addressing challenges in pulp regeneration. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis reveal the successful synthesis of PSC-Heparin. Scanning electron microscopy and X-ray diffraction show the hydroxyapatite formation can be observed on the surface of PSC-Heparin after soaking in simulated body fluid for 12 h. PSC-Heparin is capable of harvesting various endogenous GFs and sustainably releasing them over an extended duration by the enzyme-linked immunosorbent assay. Cytological experiments show that developed PSC-Heparin can facilitate the adhesion, migration, proliferation, and odontogenic differentiation of stem cells from apical papillae. Notably, the histological analysis of subcutaneous implantation in nude mice demonstrates PSC-Heparin is capable of promoting the odontoblast-like layers and pulp-dentin complex formation without the addition of exogenous GFs, which is vital for clinical applications. This work highlights an effective strategy of harvesting endogenous GFs and avoiding the involvement of exogenous GFs to achieve pulp-dentin complex regeneration, which may open a new horizon for regenerative endodontic therapy.

Periapical lesion-derived decellularized extracellular matrix as a potential solution for regenerative endodontics.

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.

Recent Advances in Functional Hydrogels for Treating Dental Hard Tissue and Endodontic Diseases.

Oral health is the basis of human health, and almost everyone has been affected by oral diseases. Among them, endodontic disease is one of the most common oral diseases. Limited by the characteristics of oral biomaterials, clinical methods for endodontic disease treatment still face large challenges in terms of reliability and stability. The hydrogel is a kind of good biomaterial with an adjustable 3D network structure, excellent mechanical properties, and biocompatibility and is widely used in the basic and clinical research of endodontic disease. This Review discusses the recent advances in functional hydrogels for dental hard tissue and endodontic disease treatment. The emphasis is on the working principles and therapeutic effects of treating different diseases with functional hydrogels. Finally, the challenges and opportunities of hydrogels in oral clinical applications are discussed and proposed. Some viewpoints about the possible development direction of functional hydrogels for oral health in the future are also put forward. Through systematic analysis and conclusion of the recent advances in functional hydrogels for dental hard tissue and endodontic disease treatment, this Review may provide significant guidance and inspiration for oral disease and health in the future.

Revascularization of a Permanent Tooth with Necrotic Pulp and Apical Periodontitis.

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.

Providing biomimetic microenvironment for pulp regeneration via hydrogel-mediated sustained delivery of tissue-specific developmental signals.

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.

De novo regeneration of dentin pulp complex mediated by Adipose derived stem cells in an immunodeficient albino rat model (Histological, histochemical and scanning electron microscopic Study).

Background: 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. Objective: 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. Material and Methods: 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. Results: 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. Conclusion: 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.

Pulp regeneration treatment using different bioactive materials in permanent teeth of pediatric subjects.

Background and Objectives: 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). Materials and Methods: 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. Results: 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%). Conclusions: 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.

Functional extracellular vesicles from SHEDs combined with gelatin methacryloyl promote the odontogenic differentiation of DPSCs for pulp regeneration.

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.

Dental pulp regeneration strategies: A review of status quo and recent advances.

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.

Potential Role of BMP7 in Regenerative Dentistry.

In recent years, the field of regenerative dentistry has garnered considerable attention for its focus on restoring and renewing damaged dental tissue. This narrative review explores the potential of bone morphogenetic protein 7 (BMP7) and its diverse applications in the regeneration of dental tissue. Recently, significant efforts have been made to understand BMP7's role in advancing regenerative dentistry. Amongst the various signalling molecules investigated for their regenerative capabilities, BMP7 emerges as a pivotal candidate, demonstrating the ability to stimulate the regeneration of dental pulp, periodontal, craniofacial, and alveolar bone tissues for dental implant placement. Whilst BMP7 exhibits significant promise as a therapeutic agent in regenerative dentistry, further research and clinical trials are necessary to fully unlock its potential and optimise its clinical effectiveness in addressing diverse dental and craniofacial conditions. This review highlights BMP7's substantial potential and emphasises the ongoing need for continued research to effectively harness its clinical utility in diverse dental and craniofacial contexts.

Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration.

Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.

Carbon Dot-Based Photo-Cross-Linked Gelatin Methacryloyl Hydrogel Enables Dental Pulp Regeneration: A Preliminary Study.

An essential factor in tooth nutritional deficits and aberrant root growth is pulp necrosis. Removing inflammatory or necrotic pulp tissue and replacing it with an inert material are the most widely used therapeutic concepts of endodontic treatment. However, pulp loss can lead to discoloration, increased fracture risk, and the reinfection of the damaged tooth. It is now anticipated that the pulp-dentin complex will regenerate through a variety of application methods based on human dental pulp stem cells (hDPSC). In order to create a photo-cross-linked gelatinized methacrylate hydrogel, GelMA/EUO-CDs-E (ECE), that is biodegradable and injectable for application, we created a novel nanoassembly of ECE based on eucommia carbon dots (EUO-CDs) and epigallocatechin gallate (EGCG). We then loaded it onto gelatin methacryloyl (GelMA) hydrogel. We have evaluated the material and examined its in vivo and in vitro angiogenesis-promoting potential as well as its dentin differentiation-enabling characteristics. The outcomes of the experiment demonstrated that GelMA/ECE was favorable to cell proliferation and enhanced hDPSC's capacity for angiogenesis and dentin differentiation. The regeneration of vascular-rich pulp-like tissues was found to occur in vivo when hDPSC-containing GelMA/ECE was injected into cleaned human root segments (RS) for subcutaneous implantation in nude mice. This suggests that the injectable bioscaffold is appropriate for clinical use in pulp regenerative medicine.

Discoloration after revascularization using calcium phosphosilicate-based bioceramic versus mineral trioxide aggregate in necrotic immature permanent anterior teeth: A Randomized clinical trial.

Aim: 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. Materials and Methods: 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. Results: 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. Conclusions: Both Totalfill bioceramic putty and WMTA can be used successfully as coronal plug in esthetic areas.

Long-term Success of Regenerative Endodontic Procedures.

Background: Regenerative endodontic procedures (REPs) have emerged as a transformative approach to treating immature permanent teeth with necrotic pulp tissue. Materials and Methods: A prospective study was conducted, enrolling 100 patients with immature permanent teeth requiring REPs. All procedures were performed by a single experienced endodontist following established protocols. Patients were followed up for a minimum of 5 years' post-treatment. Clinical examinations, radiographic assessments, and patient-reported outcomes were recorded at regular intervals. Data were analyzed using statistical methods to determine the success rates, complications, and factors influencing long-term outcomes. Results: The results of this original research reveal a significant and sustained success rate for REPs. After a minimum follow-up period of 5 years, an arbitrary value of 92% for tooth survival was achieved. Radiographic assessments demonstrated consistent healing of apical lesions, and continued root development was observed in the majority of cases. Patient-reported outcomes indicated a high level of satisfaction with the procedure. Complications such as crown discoloration and tooth fracture occurred in a minority of cases but were effectively managed without compromising the overall success of REPs. Conclusion: This original research provides strong evidence for the long-term success of REPs in the treatment of immature permanent teeth with necrotic pulp tissue. The high tooth survival rate, continued root development, and patient satisfaction support the efficacy of REPs as a reliable treatment option.

Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review.

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. DISCUSSION: 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. OTHER: 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).

Does the use of different scaffolds have an impact on the therapeutic efficacy of regenerative endodontic procedures? A systematic evaluation and meta-analysis.

BACKGROUND: In the regenerative endodontic procedures, scaffolds could influence the prognosis of affected teeth. Currently, there is controversy regarding the postoperative evaluation of various scaffolds for pulp regeneration. The objective of this study was to access whether other scaffolds, used alone or in combination with blood clot (BC), are more effective than BC in regenerative endodontic procedures. METHODS: We systematically search the PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Google Scholar databases. Randomized controlled trials examining the use of BC and other scaffold materials in the regenerative endodontic procedures were included. A random effects model was used for the meta-analysis. The GRADE method was used to determine the quality of the evidence. RESULTS: We screened 168 RCTs related to young permanent tooth pulp necrosis through electronic and manual retrieval. A total of 28 RCTs were related to regenerative endodontic procedures. Ultimately, 12 articles met the inclusion criteria and were included in the relevant meta-analysis. Only 2 studies were assessed to have a low risk of bias. High quality evidence indicated that there was no statistically significant difference in the success rate between the two groups (RR=0.99, 95% CI=0.96 to 1.03; 434 participants, 12 studies); low-quality evidence indicated that there was no statistically significant difference in the increase in root length or root canal wall thickness between the two groups. Medium quality evidence indicated that there was no statistically significant difference in pulp vitality testing between the two groups. CONCLUSIONS: For clinical regenerative endodontic procedures, the most commonly used scaffolds include BC, PRP, and PRF. All the different scaffolds had fairly high clinical success rates, and the difference was not significant. For regenerative endodontic procedures involving young permanent teeth with pulp necrosis, clinical practitioners could choose a reasonable scaffold considering the conditions of the equipment and patients.