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.

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.

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.

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.

Recent advancements in hydrogels as novel tissue engineering scaffolds for dental pulp regeneration.

Although conventional root canal treatment offers an effective therapeutic solution, it negatively affects the viability of the affected tooth. In recent years, pulp regeneration technology has emerged as a novel method for treating irreversible pulpitis due to its ability to maintain tooth vitality. The successful implementation of this technique depends on scaffolds and transplantation of exogenous stem cells or recruitment of endogenous stem cells. Accordingly, the three-dimensional structure and viscoelastic characteristics of hydrogel scaffolds, which parallel those of the extracellular matrix, have generated considerable interest. Furthermore, hydrogels support the controlled release of regenerative drugs and to load a wide variety of bioactive molecules. By integrating antibacterial agents into the hydrogel matrix and stimulating an immune response, root canal disinfection can be significantly improved and the rate of pulp regeneration can be accelerated. This review aims to provide an overview of the clinical applications of hydrogels that have been reported in the last 5 years, and offer a comprehensive summary of the different approaches that have been utilized for the optimization of hydrogel scaffolds for pulp regeneration. Advancements and challenges in pulp regeneration using hydrogels treating aged teeth are discussed.

Photosensitive Hydrogels Encapsulating DPSCs and AgNPs for Dental Pulp Regeneration.

OBJECTIVE: Pulp regeneration with bioactive dentin-pulp complex has been a research hotspot in recent years. Stem cell therapy provided an interest strategy to regenerate the dental-pulp complex. Hence, this study aimed to evaluate the effects of photosensitive gelatin methacrylate (GelMA) hydrogel encapsulating dental pulp stem cells (DPSCs) and silver nanoparticles (AgNPs) for dental pulp regeneration in vitro. METHODS: First, the AgNPs@GelMA hydrogels were prepared by lithium phenyl-2,4,6-trimethyl-benzoyl phosphinate (LAP) initiation via blue-light emitting diode light. The physical and chemical properties of AgNPs@GelMA hydrogels were comprehensively analysed via scanning electron microscopy (SEM), and mechanical characterisation, such as swelling ability, degradation properties, and AgNP release profile. Then, AgNPs@GelMA hydrogels encapsulated DPSCs were used to establish an AgNPs@GelMA biomimetic complex, further analysing its biocompatibility, antibacterial properties, and angiogenic capacity in vitro. RESULTS: The results indicated that GelMA hydrogels demontrated optimal characteristics with a monomer:LAP ratio of 16:1. The physico-chemical properties of AgNPs@GelMA hydrogels did not change significantly after loading with AgNPs. There was no significant difference in AgNP release rate amongst different concentrations of AgNPs@GelMA hydrogels. Fifty to 200 µg/mL AgNPs@GelMA hydrogels could disperse E faecalis biofilm and reduce its metabolic activity . Furthermore, cell proliferation was arrested in 100 and 200 µg/mL AgNPs@GelMA hydrogels. The inhibition of 50 µg/mL AgNPs@GelMA hydrogels on E faecalis biofilm was above 50%, and the cell viability of the hydrogels was higher than 90%. The angiogenesis assay indicated that AgNPs@GelMA hydrogels encapsulating DPSCs could induce the formation of capillary-like structures and express angiogenic markers CD31, vascular endothelial growth factor , and von willebrand factor (vWF) in vitro. CONCLUSIONS: Results of this study indicate that 50 µg/mL AgNPs@GelMA hydrogels encapsulating DPSCs had significant antibacterial properties and angiogenic capacity, which could provide a significant experimental basis for the regeneration of the dentin-pulp complex.

Allogeneic Bone Marrow Mesenchymal Stromal Cell Transplantation Induces Dentin Pulp Complex-like Formation in Immature Teeth with Pulp Necrosis and Apical Periodontitis.

INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.

Effect of pulp capping materials on odontogenic differentiation of human dental pulp stem cells: An in vitro study.

OBJECTIVES: Migration and differentiation of human dental pulp stem cells (hDPSCs) is a vital and key factor in the success of reparative dentin formation for maintenance of pulp vitality. Pulp capping materials are used to stimulate DPSCs to induce new dentin formation. Thus, the aim of the present study was to compare the response of DPSCs to four commercially available pulp capping materials: a bioactive bioceramic (Material 1), a nonresinous ready-to-use bioceramic cement (Material 2), a bioactive composite (Material 3), and a biocompatible, dual-cured, resin-modified calcium silicate (Material 4). MATERIALS AND METHODS: hDPSCs were isolated and cultured from freshly extracted teeth and were then characterized by flow cytometry and multilineage differentiation. Discs prepared from pulp capping materials were tested with hDPSCs and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, cell migration assay and odontogenic differentiation assay was performed. Expression of osteogenic markers (osteopontin, RUNX family transcription factor 2, osteocalcin) and the odontogenic marker (dentin sialophosphoprotein) was detected using reverse transcription-polymerase chain reaction. RESULTS: Materials 1, 2, and 3 generated more cell viability than Material 4. Furthermore, Material 4 showed the least wound exposure percentage, while Material 3 showed the highest percentage. Enhanced mineralization was found in hDSCPs cultured with Material 3, followed by Material 1, and then Material 2, while Material 4 revealed the least calcified mineralization. CONCLUSIONS: The results of this study were inconclusive regards contemporary bioceramic materials designed for vital pulp therapy as they have different effects on hDPSC. Further testing for cytotoxicity using live-dead staining, animal experiments, clinical trials, and independent analyses of these biomaterials is necessary for clinicians to make an informed decision for their use.

Injectable Xenogeneic Dental Pulp Decellularized Extracellular Matrix Hydrogel Promotes Functional Dental Pulp Regeneration.

The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal regenerative microenvironment and capable of accommodating intricate root canal systems. This study utilized porcine dental pulp to derive the decellularized extracellular matrix (dECM) via appropriate decellularization protocols. The resultant dECM was dissolved in an acid pepsin solution to form dECM hydrogels. The analysis encompassed evaluating the microstructure and rheological properties of dECM hydrogels and evaluated their biological properties, including in vitro cell viability, proliferation, migration, tube formation, odontogenic, and neurogenic differentiation. Gelatin methacrylate (GelMA) hydrogel served as the control. Subsequently, hydrogels were injected into treated dentin matrix tubes and transplanted subcutaneously into nude mice to regenerate dental pulp tissue in vivo. The results showed that dECM hydrogels exhibited exceptional injectability and responsiveness to physiological temperature. It supported the survival, odontogenic, and neurogenic differentiation of dental pulp stem cells in a 3D culture setting. Moreover, it exhibited a superior ability to promote cell migration and angiogenesis compared to GelMA hydrogel in vitro. Additionally, the dECM hydrogel demonstrated the capability to regenerate pulp-like tissue with abundant blood vessels and a fully formed odontoblast-like cell layer in vivo. These findings highlight the potential of porcine dental pulp dECM hydrogel as a specialized scaffold material for dental pulp regeneration.

Prevascularization techniques for dental pulp regeneration: potential cell sources, intercellular communication and construction strategies.

One of the difficulties of pulp regeneration is the rapid vascularization of transplanted engineered tissue, which is crucial for the initial survival of the graft and subsequent pulp regeneration. At present, prevascularization techniques, as emerging techniques in the field of pulp regeneration, has been proposed to solve this challenge and have broad application prospects. In these techniques, endothelial cells and pericytes are cocultured to induce intercellular communication, and the cell coculture is then introduced into the customized artificial vascular bed or induced to self-assembly to simulate the interaction between cells and extracellular matrix, which would result in construction of a prevascularization system, preformation of a functional capillary network, and rapid reconstruction of a sufficient blood supply in engineered tissue after transplantation. However, prevascularization techniques for pulp regeneration remain in their infancy, and there remain unresolved problems regarding cell sources, intercellular communication and the construction of prevascularization systems. This review focuses on the recent advances in the application of prevascularization techniques for pulp regeneration, considers dental stem cells as a potential cell source of endothelial cells and pericytes, discusses strategies for their directional differentiation, sketches the mechanism of intercellular communication and the potential application of communication mediators, and summarizes construction strategies for prevascularized systems. We also provide novel ideas for the extensive application and follow-up development of prevascularization techniques for dental pulp regeneration.

Decellularized rat submandibular gland as an alternative scaffold for dental pulp regeneration.

Introduction: Decellularized extracellular matrix has been recognized as an optimal scaffold for dental pulp regeneration. However, the limited amount of native dental pulp tissue restricts its clinical applications. The submandibular gland shares some basic extracellular matrix components and characteristics with dental pulp. However, whether decellularized submandibular gland extracellular matrix (DSMG) can be used as an alternative scaffold for dental pulp regenerative medicine is unclear. Methods: Thus, we successfully decellularized the whole rat submandibular gland and human dental pulp, and then conducted in vitro and in vivo studies to compare the properties of these two scaffolds for dental pulp regeneration. Results: Our results showed that extracellular matrix of the submandibular gland had great similarities in structure and composition with that of dental pulp. Furthermore, it was confirmed that the DSMG could support adhesion and proliferation of dental pulp stem cells in vitro. In vivo findings revealed that implanted cell-seeded DSMG formed a vascularized dental pulp-like tissue and expressed markers involved in dentinogenesis and angiogenesis. Discussion: In summary, we introduced a novel accessible biological scaffold and validated its effectiveness as an extracellular matrix-based tissue engineering scaffold for dental pulp regenerative therapy.

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration-Bioactive Scaffolds.

Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp's nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary.

Epigenetic regulation of dental-derived stem cells and their application in pulp and periodontal regeneration.

Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue engineering. An increasing number of dental-derived stem cells have been discovered recently, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), stem cells from apical papilla (SCAPs), dental follicle precursor cells (DFPCs), and periodontal ligament stem cells (PDLSCs). These stem cells have significant application prospects in tissue regeneration because they are found in an abundance of sources, and they have good biocompatibility and are highly effective. The biological functions of dental-derived stem cells are regulated in many ways. Epigenetic regulation means changing the expression level and function of a gene without changing its sequence. Epigenetic regulation is involved in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells. Existing studies have shown that dental-derived stem cells are also regulated by epigenetic modifications. Pulp and periodontal regeneration refers to the practice of replacing damaged pulp and periodontal tissue and restoring the tissue structure and function under normal physiological conditions. This treatment has better therapeutic effects than traditional treatments. This article reviews the recent research on the mechanism of epigenetic regulation of dental-derived stem cells, and the core issues surrounding the practical application and future use of pulp and periodontal regeneration.

Characterization of the Expression and Role of Histone Acetylation and Deacetylation in Dental Pulp Cells.

Histone acetylation and deacetylation of DNA-associated proteins have been shown to alter the architecture of chromatin, affecting gene expression and controlling a wide range of biological events. These events are balanced by two sets of cellular enzymes, histone-deacetylases (HDACs) and histone acetyl-transferases (HATs). Pharmacological inhibition of histone-deacetylases (HDACs) using HDAC-inhibitors (HDACis) has been shown to promote dental pulp cell reparative processes with therapeutic implications in various fields including regenerative dentistry. To date, pan-HDACi have generally been used rather than isoform-specific HDACi targeting, despite the fact that HDAC-specific inhibitors have been developed to target HDACs in several tissues. To identify potential therapeutic targets in the tooth, the expression and distribution of HDAC-isoforms need to be analyzed. This chapter focuses on techniques to analyze expression, location, and distribution of individual HDAC-isoforms under mineralizing conditions using both histology and cell biology, along with a description of basic techniques for culturing and mineralization of rodent dental pulp cells.

HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism.

Stem cell-based therapeutics is a promising strategy in dental pulp regeneration. However, low cell viability after transplantation in vivo due to the ischemic microenvironment is still a critical challenge for future clinical application. With the aim of improving postimplantation cell survival and pulp tissue regeneration, stem cells from human exfoliated deciduous teeth (SHED) were preconditioned to a hypoxic condition by hypoxia-inducible factor 1α (HIF-1α) stabilization via knockdown of prolyl hydroxylase domain-containing protein 2 (PHD2) using lentiviral short hairpin RNA. HIF-1α-stabilized SHED were encapsulated in PuraMatrix hydrogel, injected into root canals of human tooth fragments, and implanted in the subcutaneous space of immunodeficient mice. After 28 d, enhanced dental pulp-like tissue formation was observed with a significantly higher level of vascularization, which could be attributed to both endothelial differentiation of SHED and recruitment of host blood vessels. Furthermore, dentin-like tissue formation in vivo and accelerated odontogenic/osteogenic differentiation both in vivo and in vitro were observed. At 7 d postimplantation, significantly less DNA damage and higher Ki67 expression were detected in the HIF-1α-stabilized SHED group compared with the control SHED. Accordingly, cell viability assay and staining for Ki67 and apoptotic cells in vitro showed that HIF-1α stabilization could decrease cell apoptosis and enhance cell survival significantly. We demonstrated that PI3K/AKT pathway activation had resulted in low caspase 3 expression in HIF-1α-stabilized SHED in hypoxic conditions. Furthermore, we found that HIF-1α-induced cell survival could also be attributed to the upregulated expression of PDK1, HK2, and Glut1, which contributes to the maintenance of reactive oxygen species homeostasis and metabolic adaptation in hypoxia. In addition, we identified Smad7 as 1 of the top 3 upregulated genes through RNA sequencing in HIF-1α-stabilized SHED and demonstrated its essential role in HK2 and Glut1 upregulation. Taken together, HIF-1α stabilization enhances cell survival of SHED through modulating various target genes and potential signaling pathways, as well as odontogenic tissue formation during dental pulp regeneration, which could benefit stem cell-based therapy in general.

Angiogenesis during coronal pulp regeneration using rat dental pulp cells: Neovascularization in rat molars in vivo and proangiogenic dental pulp cell-endothelial cell interactions in vitro.

Background/purpose: Angiogenesis is considered a crucial event for dental pulp regeneration. The purpose of this study was to demonstrate neovascularization during coronal pulp regeneration in rat molars using rat dental pulp cells (rDPCs) and to examine whether rDPC-endothelial cell interactions promote proangiogenic capacity in vitro. Materials and methods: Maxillary first molars of Wistar rats (n = 42) were pulpotomized and rDPCs isolated from incisors were implanted with a porous poly (l-lactic acid) (PLLA) scaffold and hydrogel (Matrigel). After 3, 7, and 14 days, coronal pulp tissues were examined histologically and by nestin and CD146 immunohistochemistry. rDPCs and rat dermal microvascular endothelial cells (rDMECs) were cocultured for 4 days and vascular endothelial growth factor (VEGF) synthesis and angiogenic factor gene expression were determined by enzyme-linked immunosorbent assays and real-time polymerase chain reaction, respectively. Effects of cocultured medium on tube formation by rDMECs were also evaluated. Results: Implantation of rDPC/PLLA/Matrigel induced coronal pulp regeneration with dentin bridge formation and arrangement of nestin-positive odontoblast-like cells at 14 days. PLLA/Matrigel without rDPCs did not induce pulp regeneration. CD146-positive blood vessels increased in density in the remaining pulp tissues at 3 and 7 days, and in the regenerated pulp tissue at 14 days. rDPC/DMEC coculture significantly promoted VEGF secretion and mRNA expression of nuclear factor-kappa B, angiogenic chemokine CXCL1, and chemokine receptor CXCR1. Cocultured medium significantly promoted tube formation. Conclusion: Coronal pulp regeneration with rDPC/PLLA/Matrigel was accompanied by neovascularization. rDPC-rDMEC interactions may promote angiogenic activity represented by proangiogenic factor upregulation and tube formation in vitro.

Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration.

Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.

Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives.

Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.

Evaluation of a hyaluronic acid hydrogel (Restylane Lyft) as a scaffold for dental pulp regeneration in a regenerative endodontic organotype model.

Scaffolds are crucial elements for dental pulp regeneration. Most of the currently used scaffolds in regenerative endodontic procedures (REPs) are unsuitable for chairside clinical use. This study aimed to evaluate the effect of an injectable synthetic scaffold (Restylane Lyft) on human bone marrow mesenchymal stem cell (hBMSC) viability, proliferation, and osteo/dentinogenic differentiation in a regenerative endodontic organotype model (REM). hBMSC were loaded in an REM either alone (hBMSC group) or mixed with the Restylane Lyft scaffold (Restylane/hBMSC group) and cultured in basal culture medium (n = 9/group). hMSC on culture plates served as controls. Cell viability and proliferation were measured using AlamarBlue assay. The loaded REM was cultured in an osteogenic differentiation medium to measure alkaline phosphatase activity (ALP) and examine the expression of the osteo/dentinogenic markers using real-time reverse transcriptase polymerase chain reaction. Cell viability in all groups increased significantly over 5 days. The Restylane/hBMSC group showed significantly higher ALP activity and dentin sialophosphoprotein, osteocalcin, and bone sialoprotein genes expression than the hBMSC and the control groups. Restylane Lyft, a hyaluronic acid (HA) injectable, FDA-approved hydrogel, maintained cell viability and proliferation and promoted osteo/dentinogenic differentiation of hBMSC when cultured in an REM. Henceforth, it could be a promising chairside scaffold material for REPs.