Dental Tissue Regeneration Research Articles

Dentin regeneration based on tooth tissue engineering: A review.

Missing or damaged teeth due to caries, genetic disorders, oral cancer, or infection may contribute to physical and mental impairment that reduces the quality of life. Despite major progress in dental tissue repair and those replacing missing teeth with prostheses, clinical treatments are not yet entirely satisfactory, as they do not regenerate tissues with natural teeth features. Therefore, much of the focus has centered on tissue engineering (TE) based on dental stem/progenitor cells to create bioengineered dental tissues. Many in vitro and in vivo studies have shown the use of cells in regenerating sections of a tooth or a whole tooth. Tooth tissue engineering (TTE), as a promising method for dental tissue regeneration, can form durable biological substitutes for soft and mineralized dental tissues. The cell-based TE approach, which directly seeds cells and bioactive components onto the biodegradable scaffolds, is currently the most potential method. Three essential components of this strategy are cells, scaffolds, and growth factors (GFs). This study investigates dentin regeneration after an injury such as caries using TE and stem/progenitor cell-based strategies. We begin by discussing about the biological structure of a dentin and dentinogenesis. The engineering of teeth requires knowledge of the processes that underlie the growth of an organ or tissue. Then, the three fundamental requirements for dentin regeneration, namely cell sources, GFs, and scaffolds are covered in the current study, which may ultimately lead to new insights in this field.

38 - Dexamethasone-loaded Bacterial Nanocellulose for Promoting Dental Tissue Regeneration

38 - Dexamethasone-loaded Bacterial Nanocellulose for Promoting Dental Tissue Regeneration

Current Application of iPS Cells in the Dental Tissue Regeneration.

When teeth and periodontal tissues are severely damaged by severe caries, trauma, and periodontal disease, such cases may be subject to tooth extraction. As tooth loss leads to the deterioration of quality of life, the development of regenerative medicine for tooth and periodontal tissue is desired. Induced pluripotent stem cells (iPS cells) are promising cell resources for dental tissue regeneration because they offer high self-renewal and pluripotency, along with fewer ethical issues than embryonic stem cells. As iPS cells retain the epigenetic memory of donor cells, they have been established from various dental tissues for dental tissue regeneration. This review describes the regeneration of dental tissue using iPS cells. It is important to mimic the process of tooth development in dental tissue regeneration using iPS cells. Although iPS cells had safety issues in clinical applications, they have been overcome in recent years. Dental tissue regeneration using iPS cells has not yet been established, but it is expected in the future.

Extracellular vesicles: A potential future strategy for dental and maxillofacial tissue repair and regeneration.

Extracellular vesicles (EVs), nano-sized bilayer membrane structures containing lipids, proteins and nucleic acids, play key roles in intercellular communication. Compared to stem cells, EVs have lower tumorigenicity and immunogenicity, are easier to manage and cause fewer ethic problems. In recent years, EVs have emerged as a potential solution for tissue regeneration in stomatology through cell-free therapies. The present review focuses on the role of EVs in dental and maxillofacial tissue repair and regeneration, including in dental and periodontal tissue, maxilla and mandible bone, temporomandibular joint cartilage, peripheral nerve and soft tissue. We also make a brief overview on the mechanism of EVs performing functions. However, limitations and challenges in clinical application of EVs still exist and should be addressed in future researches.

Interpenetrating Low-Molecular Weight Hyaluronic Acid in Hyaluronic Acid-Based In Situ Hydrogel Scaffold for Periodontal and Oral Wound Applications.

Tissues engineering has gained a lot of interest, since this approach has potential to restore lost tooth-supporting structures, which is one of the biggest challenges for periodontal treatment. In this study, we aimed to develop an in situ hydrogel that could conceivably support and promote the regeneration of lost periodontal tissues. The hydrogel was fabricated from methacrylated hyaluronic acid (MeHA). Fragment/short-chain hyaluronic acid (sHA) was incorporated in this hydrogel to encourage the bio-synergistic effects of two different molecular weights of hyaluronic acid. The physical properties of the hydrogel system, including gelation time, mechanical profile, swelling and degrading behavior, etc., were tested to assess the effect of incorporated sHA. Additionally, the biological properties of the hydrogels were performed in both in vitro and in vivo models. The results revealed that sHA slightly interfered with some behaviors of networking systems; however, the overall properties were not significantly changed compared to the base MeHA hydrogel. In addition, all hydrogel formulations were found to be compatible with oral tissues in both in vitro and in vivo models. Therefore, this HA-based hydrogel could be a promising delivery system for low molecular weight macromolecules. Further, this approach could be translated into the clinical applications for dental tissue regeneration.

Hepatocyte Growth Factor Promotes Differentiation Potential and Stress Response of Human Stem Cells from Apical Papilla

Harsh local microenvironment, such as hypoxia and lack of instructive clues for transplanted stem cells, presents the serious obstacle for stem cell therapies’ efficacy. Therefore, continued efforts have been taken to improve stem cells’ viability and plasticity. Hepatocyte growth factor (HGF) has previously been reported to mitigate the complications of various human diseases in animal model studies and in some clinical trials. Besides, human stem cells from the root apical papilla (SCAP) are deemed a better resource of mesenchymal stem cells due to derived stem cells holding greater amplification ability in vitro compared with those from other dental resources. To move forward, evaluating effects and understanding underlying molecular mechanisms of HGF on SCAP for periodontal regeneration are needed. In this study, HGF was transgenically expressed in SCAP, and it was found that HGF enhanced osteo/dentinogenic differentiation capacity of SCAP compared with those of non-treated control in an ectopic mineralization model. Moreover, HGF reduced the apoptosis of SCAP under both normoxic and hypoxic conditions, whereas the combination of HGF and hypoxia exposure had inhibitory effects on cell proliferation during an 8-day in vitro culture period. Transcriptome analysis further revealed that suppressed cell cycle progression and activated BMP/TGFβ, Hedgehog, WNT, FGF, HOX, and other morphogen family members result upon HGF overexpression, which may render SCAP recapitulate part of neural crest stem cell characteristics. Moreover, strengthened stress response modulation such as unfolded protein response, macroautophagy, and anti-apoptotic molecules might explain the increased viability of SCAP. In all, our results imply that these potential mechanisms underlying HGF-promoting SCAP differentiation could be further elucidated and harnessed to improve periodontal tissue regeneration.

The role of different macrophages-derived conditioned media in dental pulp tissue regeneration

Macrophages have been reported to play important roles in tissue repair and regeneration. While it is known that macrophages are present in the dental pulp, their role in dental pulp regeneration is not fully understood. In the present study, we investigated the effects of different phenotype macrophages conditioned medium on the cellular behaviors of hDPSCs and their extracellular matrix (cell sheets) in vitro. Moreover, twenty-four root fragments inserted with cell sheets cultured with different conditioned media were placed into the back subcutaneous space of 6–8-week-old male BALB/c nude mouse. The regenerated tissues in the root fragments were assessed via histologic analysis after 8 weeks of transplantation. M2 macrophages could promote the proliferation, migration, and osteogenic differentiation of hDPSCs. Dental pulp-like tissue with an odontoblast-like layer lining the dentinal surface and well-arranged collagen fibers was harvested in root fragment combined with M2 conditioned medium cultured cell sheet, whereas a large amount of calcium salt deposition and disorganization of collagen fibers were observed in root fragments combined with M1 conditioned medium cultured cell sheet. Therefore, promoting the transformation of M1 into M2 macrophage in dental pulp tissue regeneration may be a potential way for dental pulp regeneration via functional healing.

The Regenerative Potential of Decellularized Dental Pulp Extracellular Matrix: A Systematic Review.

Introduction: The regeneration of dental pulp remains a challenge. Although several treatment modalities have been proposed to promote pulpal regeneration, these treatments have several drawbacks. More recently, decellularized dental pulp extracellular matrix (DP-ECM) has been proposed to regenerate dental pulp. However, to date, no systematic review has summarized the overall outcome and assessed the available literature focusing on the endodontic use of DP-ECM. The aim of this systematic review is to critically appraise the literature, summarize the overall outcomes, and provide clinical recommendations about DP-ECM. Methodology: Following the Participants Intervention Control and Outcomes (PICO) principle, a focused question was constructed before conducting a search of the literature and of electronic research databases and registers. The focused question was: ‘Compared to controls, does decellularized dental pulp extracellular matrix (DP-ECM) stimulate the regeneration of dental pulp cells and tissue?’ Quality assessment of the studies was carried out using Guidelines for Reporting Pre-Clinical in Vitro Studies on Dental Materials and ARRIVE guidelines. Results: 12 studies were included in this review. Data from five in vitro experiments and eight in vivo experiments were extracted and the quality of the experiments was assessed. In majority of the studies, DP-ECM appeared to have stimulated pulpal regeneration. However, several sources of bias and methodological deficiencies were found during the quality assessment. Conclusion: Within the limitations of this review and the included studies, it may be concluded that there is insufficient evidence to deduce the overall efficacy of DP-ECM for pulpal regeneration. More research, clinical and pre-clinical, is required for more conclusive evidence.

Effects of Aspirin on Odontogenesis of Human Dental Pulp Cells and TGF-β1 Liberation from Dentin In Vitro.

Aim This in vitro study aimed to investigate the roles of aspirin (ASA) and its concentrations on the odontogenesis of human dental pulp cells (HDPCs) and to investigate the influence of ASA on TGF-β1 liberation from dentin. Methodology. HDPCs were cultured in a culture medium with 25, 50, 75, 100, and 200 μ·g/mL ASA and 0 μ·g/mL ASA as a control. The mitochondrial activity of HDPCs was assessed using an MTT assay. Crystal violet staining and triton were used to evaluate cell proliferation rates. ALP activity was measured with a fluorometric assay. Expressions of DSP and RUNX2 were determined with the ELISA. DSP and RUNX2 mRNA levels were measured with RT-qPCR. Alizarin red staining was conducted to evaluate the mineralized nodule formation. Dentin slices were submerged in PBS (negative control), 17% EDTA (positive control), and ASA before collecting the solution for TGF-β1 quantification by the ELISA. The data were analyzed by the t-tests and ANOVA, followed by the Tukey post hoc tests. P values < 0.05 were considered statistically significant. Results The results showed that 25–50 μ·g/mL ASA promoted mitochondrial activity of HDPCs at 72 h (P < 0.05) and yielded significantly higher proliferation rates of HDPCs than the control at 14d and 21d (P < 0.001). All concentrations of ASA promoted odontogenic differentiation of HDPCs by enhancing the levels of DSP and RUNX2, their mRNA expression, and mineralization in a dose-dependent manner. Also, ASA yielded significantly higher TGF-β1 liberation after conditioning dentin for 5 min (25, 200 μ·g/mL; P < 0.001) and 10 min (200 μ·g/mL; P < 0.05). Conclusions This in vitro study demonstrated that ASA, especially in high concentrations, promoted the odontogenesis of HDPCs and TGF-β1 liberation from dentin, showing the potential of being incorporated into the novel pulp capping materials for dental tissue regeneration.

Pluripotency of periodontal ligament and dental pulp cells is induced by intercellular communication via the CDX2/Oct-4/Sox2 pathway.

BackgroundIntercellular communication in the environments of mature or aged cells can restore and regenerate their function and promote the expression of pluripotency markers. The regeneration of dental tissue is stimulated by periodontal ligament cells (PDLCs) and dental pulp cells (DPCs). However, the communication networks between the cells and their microenvironments are poorly understood.MethodsIn this study, gene expression was analyzed by polymerase chain reaction, and chromatin immunoprecipitation assays, dual-luciferase assays, and electrophoretic mobility shift assays were used to analyze the signaling pathways associated with pluripotency after the knockdown or overexpression of caudal-type homeobox transcription factor 2 (CDX2).ResultsElevated levels of SRY-box transcription factor 2 (Sox2) and octamer-binding transcription factor 4 (Oct-4) were observed in the co-culture system, while the levels of CDX2 were significantly reduced. The overexpression of CDX2 promoted cell apoptosis and reduced the synthesis stage of the cell cycle. CDX2 was shown to bind directly to the promoter regions of Sox2 and Oct-4. The silencing of CDX2 promoted calcium deposition, adipogenic differentiation, and elevated alkaline phosphatase (ALP) activity in the DPCs.ConclusionsThese findings demonstrate the enhancement of DPC and PDLC pluripotency by intercellular communication. CDX2 plays a significant part in the regulation of DPC and PDLC pluripotency via its regulation of Oct-4 and Sox2 expression.

Strategies of Bioceramics, Bioactive Glasses in Endodontics: Future Perspectives of Restorative Dentistry.

Prevalently, there is a primary strategy to cure caries using restorative materials notably bioceramics. Existing synthetic materials stimulate natural tooth structure with acceptable interfacial bonding and esthetic and biomechanical qualities with better durability. Several bioceramics have been introduced and investigated for their potentialities as restorative materials. Biomineralization of tooth initiates repair and regeneration of natural dental tissue and reinstating the integrity of periodontium. In the evolution of bioceramics in the aspects of different essential composition for dental application, recent technology and modern strategies revolutionize the restorative dentistry. Bioglass is one among the important bioceramics as a restorative material, and by regulating the properties of the material, it is possible to construct improved formulation towards restoration. This article reviews the current revolution of endodontics, existing restorative materials, and technologies to be achieve for engineering materials with the better design.

A Bibliometric Analysis of Electrospun Nanofibers for Dentistry.

Electrospun nanofibers have been widely used in dentistry due to their excellent properties, such as high surface area and high porosity, this bibliometric study aimed to review the application fields, research status, and development trends of electrospun nanofibers in different fields of dentistry in recent years. All of the data were obtained from the Web of Science from 2004 to 2021. Origin, Microsoft Excel, VOSviewer, and Carrot2 were used to process, analyze, and evaluate the publication year, countries/region, affiliations, authors, citations, keywords, and journal data. After being refined by the year of publication, document types and research fields, a total of 378 publications were included in this study, and an increasing number of publications was evident. Through linear regression calculations, it is predicted that the number of published articles in 2022 will be 66. The most published journal about electrospun dental materials is Materials Science & Engineering C-Materials for Biological Applications, among the six core journals identified, the percent of journals with Journal Citation Reports (JCR) Q1 was 60%. A total of 17.60% of the publications originated from China, and the most productive institution was the University of Sheffield. Among all the 1949 authors, the most productive author was Marco C. Bottino. Most electrospun dental nanofibers are used in periodontal regeneration, and Polycaprolactone (PCL) is the most frequently used material in all studies. With the global upsurge in research on electrospun dental materials, bone regeneration, tissue regeneration, and cell differentiation and proliferation will still be the research hotspots of electrospun dental materials in recent years. Extensive collaboration and citations among authors, institutions and countries will also reach a new level.

Potential applications of medicinal herbs and phytochemicals in oral and dental health: Status quo and future perspectives.

Herbal therapies are utilized to treat a broad diversity of diseases all over the globe. Although no clinical studies have been conducted to demonstrate the antibacterial, antimicrobial, and antiplaque characteristics of these plants, this does not imply that they are ineffectual as periodontal treatments or anti-cariogenic drugs. However, there is a scarcity of research confirming their efficacy and worth. Herbs are utilized in dentistry as antimicrobial, antineoplastic, antiseptic, antioxidant, and analgesics agents as well as for the elimination of bad breath. In addition, the application of herbal agents in tissue engineering improved the regeneration of oral and dental tissues. This study reviews the application of medicinal herbs for the treatment of dental and oral diseases in different aspects. This article focuses on current developments in the use of medicinal herbs and phytochemicals in oral and dental health. An extensive literature review was conducted via an Internet database, mostly PubMed. The articles included full-text publications written in English without any restrictions on a date. Plants have been suggested, as an alternate remedy for oral-dental problems, and this vocation needs long-term dependability. More research on herbal medicine potential as pharmaceutical sources and/or therapies is needed.

Long non-coding RNA IGFBP7-AS1 promotes odontogenic differentiation of stem cells from human exfoliated deciduous teeth through autophagy: An in vitro study

ObjectiveIn the present study, we aimed to investigate whether long non-coding RNA (lncRNA) insulin-like growth factor binding protein 7-antisense 1 (IGFBP7-AS1) regulates the odonto-differentiation of stem cells from human exfoliated deciduous teeth (SHED) and its underlying mechanism. DesignReal-time polymerase chain reaction (PCR) and correlation analysis were used to determine the expression of IGFBP7-AS1 during odontogenesis. Alkaline phosphate staining, alizarin red S staining, and real-time PCR in vitro were performed to investigate the effects of IGFBP7-AS1 during odontogenesis. Western blot and immunostaining (with or without chloroquine treatment) were applied to detect the expression of the autophagy-related markers, microtubule-associated proteins 1A/1B light chain 3B (LC3B) and p62. The autophagy inhibitor 3-methyladenine was used to further clarify the effect of autophagy in odonto-differentiation as promoted by IGFBP7-AS1. ResultsThe expression of lncRNA IGFBP7-AS1 is significantly upregulated during odonto-differentiation of SHED and promotes odontogenesis of SHED in vitro. IGFBP7-AS1 promotes autophagy during odontogenesis. ConclusionsIGFBP7-AS1 elicits odontogenic differentiation of SHED through autophagy. Furthermore, IGFBP7-AS1 shows promise as a gene target in the regeneration of dental hard tissue and dental–pulp complex.

The functional extracellular matrix on the regulation of odontogenic differentiation of stem cells

AbstractDental defects and loss are common oral diseases that seriously affect the chewing efficiency of patients and thereby affect their health. With the development of tissue engineering technology, dental tissue regeneration has emerged as a promising technique. Cell type, extracellular matrix (ECM) environment, cytokines and other factors which affect odontogenic differentiation and dental tissue regeneration have aroused significant interest. The functional ECM consists of extracellular components that control the initiation and growth of crystal deposition and regulate the differentiation and regeneration of endogenous or exogenous stem cells in the defect site. At present, the function and regulatory mechanism of the functional ECM in this process remain poorly understood. Therefore, elucidating the effect of the functional ECM on odontogenic differentiation and its mechanism has great scientific significance and potential clinical application. This review explored functional ECM components involved in odontogenic differentiation and dental tissue regeneration.

Self-Crosslinkable Oxidized Alginate-Carboxymethyl Chitosan Hydrogels as an Injectable Cell Carrier for In Vitro Dental Enamel Regeneration.

Injectable hydrogels, as carriers, offer great potential to incorporate cells or growth factors for dental tissue regeneration. Notably, the development of injectable hydrogels with appropriate structures and properties has been a challenging task, leaving much to be desired in terms of cytocompatibility, antibacterial and self-healing properties, as well as the ability to support dental stem cell functions. This paper presents our study on the development of a novel self-cross-linkable hydrogel composed of oxidized alginate and carboxymethyl chitosan and its characterization as a cell carrier for dental enamel regeneration in vitro. Oxidized alginate was synthesized with 60% theoretical oxidation degree using periodate oxidation and characterized by Fourier Transform Infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and Ultraviolet-visible absorption spectroscopy. Then, hydrogels were prepared at three varying weight ratios of oxidized alginate to carboxymethyl chitosan (4:1, 3:1, and 2:1) through Schiff base reactions, which was confirmed by Fourier Transform Infrared spectroscopy. The hydrogels were characterized in terms of gelation time, swelling ratio, structure, injectability, self-healing, antibacterial properties, and in vitro characterization for enamel regeneration. The results demonstrated that, among the three hydrogels examined, the one with the highest ratio of oxidized alginate (i.e., 4:1) had the fastest gelation time and the lowest swelling ability, and that all hydrogels were formed with highly porous structures and were able to be injected through a 20-gauge needle without clogging. The injected hydrogels could be rapidly reformed with the self-healing property. The hydrogels also showed antibacterial properties against two cariogenic bacteria: Streptococcus mutans and Streptococcus sobrinus. For in vitro enamel regeneration, a dental epithelial cell line, HAT-7, was examined, demonstrating a high cell viability in the hydrogels during injection. Furthermore, HAT-7 cells encapsulated in the hydrogels showed alkaline phosphatase production and mineral deposition, as well as maintaining their round morphology, after 14 days of in vitro culture. Taken together, this study has provided evidence that the oxidized alginate-carboxymethyl chitosan hydrogels could be used as an injectable cell carrier for dental enamel tissue engineering applications.

Obtaining bioceramic cements for dental repair procedures based on hydroxyapatite and bismuth oxide

Introduction: The use of hydroxyapatite-based cements in dental and bone tissue regeneration procedures has shown favorable results. However, structural fragility and lower levels of radiopacity at clinical evaluation make it difficult to use in direct clinical procedures. Objective: This study aimed to synthesize a new cement with properties to be considered for use in dental repair procedures using hydroxyapatite and a hydrogel, with the addition of bismuth oxide as a radiopacifying agent. Methodology: The materials were obtained by a mixture of hydroxyapatite produced by the precipitation method, a hydrogel with carboxymethylcellulose and calcium silicate and bismuth oxide. The products were characterized by X-ray diffraction, Fourrier transform X-ray fluorescence, scanning electron microscopy, setting time, pH and radiographic appearance. Data were analyzed using Jamovi® software version 1.6 to calculate absolute frequencies, as well as measures of central tendency and variability. Results: The proposed cements obtained presented phase compositions without alterations in the composites, with a nanometric porous structure. Basic pH contributes to its bioactivity and antimicrobial action. The drying time of the proposed cements was prolonged. From the radiographs, the cement containing bismuth oxide was radiopaque when compared to the cement without this component. Conclusion: A new dental cement based on hydroxyapatite and bismuth oxide was obtained, homogeneous, with satisfactory radiopacity property, enabling its analysis through radiographic examinations.

The Effects of 3-Dimensional Bioprinting Calcium Silicate Cement/Methacrylated Gelatin Scaffold on the Proliferation and Differentiation of Human Dental Pulp Stem Cells.

A calcium silicate cement/methacrylated gelatin (GelMa) scaffold has been applied in tissue engineering; however, the research on its applications in dental tissue regeneration remains lacking. We investigate the effect of this scaffold on human dental pulp stem cells (hDPSCs). hDPSCs were cultured in 3D-printed GelMa and MTA-GelMa scaffolds. Cell adhesion was evaluated using scanning electron microscopy images. Cells were cultured in an osteogenic differentiation medium, which contained a complete medium or α-MEM containing aqueous extracts of the 3D-printd GelMa or MTA-GelMa scaffold with 2% FBS, 10 mM β-glycerophosphate, 50 μg/mL ascorbic acid, and 10 nM dexamethasone; cell viability and differentiation were shown by WST-1 assay, Alizarin Red S staining, and alkaline phosphatase staining. Quantitative real-time PCR was used to measure the mRNA expression of DSPP and DMP-1. One-way analysis of variance followed by Tukey’s post hoc test was used to determine statistically significant differences, identified at p < 0.05. hDPSCs adhered to both the 3D-printed GelMa and MTA-GelMa scaffolds. There was no statistically significant difference between the GelMa and MTA-GelMa groups and the control group in the cell viability test. Compared with the control group, the 3D-printed MTA-GelMa scaffold promoted the odontogenic differentiation of hDPSCs. The 3D-printed MTA-GelMa scaffold is suitable for the growth of hDPSCs, and the scaffold extracts can better promote odontoblastic differentiation.

Electrospun Nanofibers Revisited: An Update on the Emerging Applications in Nanomedicine.

Electrospinning (ES) has become a straightforward and customizable drug delivery technique for fabricating drug-loaded nanofibers (NFs) using various biodegradable and non-biodegradable polymers. One of NF’s pros is to provide a controlled drug release through managing the NF structure by changing the spinneret type and nature of the used polymer. Electrospun NFs are employed as implants in several applications including, cancer therapy, microbial infections, and regenerative medicine. These implants facilitate a unique local delivery of chemotherapy because of their high loading capability, wide surface area, and cost-effectiveness. Multi-drug combination, magnetic, thermal, and gene therapies are promising strategies for improving chemotherapeutic efficiency. In addition, implants are recognized as an effective antimicrobial drug delivery system overriding drawbacks of traditional antibiotic administration routes such as their bioavailability and dosage levels. Recently, a sophisticated strategy has emerged for wound healing by producing biomimetic nanofibrous materials with clinically relevant properties and desirable loading capability with regenerative agents. Electrospun NFs have proposed unique solutions, including pelvic organ prolapse treatment, viable alternatives to surgical operations, and dental tissue regeneration. Conventional ES setups include difficult-assembled mega-sized equipment producing bulky matrices with inadequate stability and storage. Lately, there has become an increasing need for portable ES devices using completely available off-shelf materials to yield highly-efficient NFs for dressing wounds and rapid hemostasis. This review covers recent updates on electrospun NFs in nanomedicine applications. ES of biopolymers and drugs is discussed regarding their current scope and future outlook.

Prospect on the application of mesenchymal stem cell-derived extracellular vesicles in the regeneration of dental and maxillofacial tissues.

Extracellular vesicles (EVs) are the essential mediators of communication between different cells or tissues. EVs participate in the development, homeostasis, repair, and regeneration of tissues. Mesenchymal stem cells(MSCs) secrete a range of bioactive factors, which are important in MSC-mediated tissue regeneration. Great progress has been made in the research of EVs derived from MSCs (MSC-EVs) in the regeneration of dental and maxillofacial tissues. Emerging evidence confirmed that MSC-EVs can efficiently modulate the proliferation, differentiation, survival, and migration of stem or progenitor cells and stimulate the regeneration of the neurovascular system. MSC-EVs have been used in regenerating dental pulp, periodontium, jawbone, temporomandibular joint, and maxillofacial soft tissues. Having the advantages of low immunogenicity, versatile function, and suitability for large-scale production, EVs have excellent clinical application prospect. Along with investigations on molecular mechanisms of action and development of standard manufactory and testing systems, therapies u-sing MSC-EVs are promising strategies for regenerating dental and maxillofacial tissues.