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.

The orthodontic-endodontic interface: trauma and pulpal considerations.

The interpretation of the clinical signs and symptoms arising from the interdisciplinary relationship between orthodontics and endodontics becomes more complicated when superimposed by dental trauma. A history of dental trauma before or during orthodontic tooth movement may have implications for pulpal health and clinical outcomes. An understanding of the biology is essential for appropriate treatment planning. This review and treatment recommendations will assist dental practitioners in managing orthodontic-endodontic interactions.

Enhancing facial nerve regeneration with scaffold-free conduits engineered using dental pulp stem cells and their endogenous, aligned extracellular matrix.

Objective. Engineered nerve conduits must simultaneously enhance axon regeneration and orient axon extension to effectively restore function of severely injured peripheral nerves. The dental pulp contains a population of stem/progenitor cells that endogenously express neurotrophic factors (NTFs), growth factors known to induce axon repair. We have previously generated scaffold-free dental pulp stem/progenitor cell (DPSC) sheets comprising an aligned extracellular matrix (ECM). Through the intrinsic NTF expression of DPSCs and the topography of the aligned ECM, these sheets both induce and guide axon regeneration. Here, the capacity of bioactive conduits generated using these aligned DPSC sheets to restore function in critical-sized nerve injuries in rodents was evaluated.Approach. Scaffold-free nerve conduits were formed by culturing DPSCs on a substrate with aligned microgrooves, inducing the cells to align and deposit an aligned ECM. The sheets were then detached from the substrate and assembled into scaffold-free cylindrical tissues.Main results. In vitroanalyses confirmed that scaffold-free DPSC conduits maintained an aligned ECM and had uniformly distributed NTF expression. Implanting the aligned DPSC conduits across critical-sized defects in the buccal branch of rat facial nerves resulted in the regeneration of a fascicular nerve-like structure and myelinated axon extension across the injury site. Furthermore, compound muscle action potential and stimulated whisker movement measurements revealed that the DPSC conduit treatment promoted similar functional recovery compared to the clinical standard of care, autografts. Significance. This study demonstrates that scaffold-free aligned DPSC conduits supply trophic and guidance cues, key design elements needed to successfully promote and orient axon regeneration. Consequently, these conduits restore function in nerve injuries to similar levels as autograft treatments. These conduits offer a novel bioactive approach to nerve repair capable of improving clinical outcomes and patient quality of life.

Dentin Mechanobiology: Bridging the Gap between Architecture and Function.

It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical adaptation mechanisms within their structure to counter constant stress. Dentin, situated between enamel and pulp, plays a crucial role in mechanically supporting tooth function. Its intermediate stiffness and viscoelastic properties, attributed to its mineralized, nanofibrous extracellular matrix, provide flexibility, strength, and rigidity, enabling it to withstand mechanical loading without fracturing. Moreover, dentin's unique architectural features, such as odontoblast processes within dentinal tubules and spatial compartmentalization between odontoblasts in dentin and sensory neurons in pulp, contribute to a distinctive sensory perception of external stimuli while acting as a defensive barrier for the dentin-pulp complex. Since dentin's architecture governs its functions in nociception and repair in response to mechanical stimuli, understanding dentin mechanobiology is crucial for developing treatments for pain management in dentin-associated diseases and dentin-pulp regeneration. This review discusses how dentin's physical features regulate mechano-sensing, focusing on mechano-sensitive ion channels. Additionally, we explore advanced in vitro platforms that mimic dentin's physical features, providing deeper insights into fundamental mechanobiological phenomena and laying the groundwork for effective mechano-therapeutic strategies for dentinal diseases.

Neovascularization by DPSC-ECs in a Tube Model for Pulp Regeneration Study.

The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used. Human microvascular endothelial cells (hMVECs) were used as a positive control. DPSC-ECs formed tubules on Matrigel similar to hMVECs. Cells were mixed in fibrinogen/thrombin or mouse blood and seeded into wells of 96-well plates or injected into a tapered plastic tube (14 mm in length and 1 or 2 mm diameter of the apex opening) with the larger end sealed with MTA to simulate root canal space. Cells/gels in wells or tubes were incubated for various times in vitro and observed under the microscope for morphological changes. Samples were then fixed and processed for histological analysis to determine vessel formation. Vessel-like networks were observed in culture from 1 to 3 d after cell seeding. Cells/gels in 96-well plates were maintained up to 25 d. Histologically, both hMVECs and DPSC-ECs in 96-well plates or tubes showed intracellular vacuole formation. Some cells showed merged large vacuoles indicating the lumenization. Tubular structures were also observed resembling blood vessels. Cells appeared healthy throughout the tube except some samples (1 mm apical diameter) in the coronal third. Histological analysis also showed pulp-like soft tissue throughout the tube samples with vascular-like structures. hMVECs formed larger vascular lumen size than DPSC-ECs while the latter tended to have more lumen and tubular structure counts. We conclude that DPSC-ECs can form vascular structures and sustained in the 3-dimensional fibrin gel system in vitro. The tube model appears to be a proper and simple system simulating the root canal space for vascular formation and pulp regeneration studies.

Application of Oxygen Saturation Test after Replantation of Avulsed Immature Permanent Teeth: A Prospective Observational Study.

INTRODUCTION: The evaluation of pulp status is crucial for avulsed immature permanent teeth after replantation. In addition to commonly used clinical and radiographic examinations providing clinical evidence, the oxygen saturation test may offer valuable assistance. The aim of this study was to analyze the efficacy of a pulse oximeter in evaluating pulp status in avulsed and replanted immature permanent teeth. METHODS: A prospective observational study was performed including 51 avulsed and replanted immature permanent teeth. Routine clinical and radiographic examinations were performed and used as the basis for the diagnosis of pulp status during the 1-year follow-up period. Meanwhile, the oxygen saturation values of these teeth were recorded using a modified pulse oximeter at each visit. RESULTS: Seven teeth completed pulp revascularization (success group), whereas 44 teeth failed to revascularize (failure group). Abnormal clinical and/or radiographic manifestations in the failure group were observed at an average period of 42.7 days, which was too late because a high incidence of inflammatory root resorption (43.18%) had occurred. For oxygen saturation tests, teeth in the success group showed an immediate postreplantation oxygen value of 70.71 ± 3.35, then an upward trend starting from the 2-week postreplantation visit, and a significantly increased final value of 81.86 ± 2.34 at the 1-year visit. In contrast, no increase trend was found for teeth in the failure group because abnormal clinical and/or radiographic manifestations emerged. CONCLUSIONS: The oxygen saturation test is a reliable diagnostic method to evaluate pulp status of avulsed teeth as early as 2 weeks after replantation.

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.

Exploring approaches to pulp vitality assessment: A scoping review of nontraditional methods.

INTRODUCTION: Diagnostic procedures for pulp vitality assessment are a crucial aspect of routine dental practice. This review aims to provide a comprehensive overview of nontraditional techniques and methodologies for assessing pulp vitality, specifically exploring promising approaches that are currently not used in dental practice. METHODS: The study protocol was registered a priori (https://osf.io/3m97z/). An extensive electronic search was conducted across multiple databases, including MEDLINE via PubMed, Scopus, Web of Science, and Embase. Inclusion criteria were guided by the research question based on the PCC model as follows: "What are the potential nontraditional techniques (Concept) for assessing pulp vitality (Population) in the field of endodontics or clinical practice (Context)?" Studies were included that explored possible approaches to pulp vitality assessment, utilizing a range of techniques, whilst any studies using traditional pulp tests (cold, heat, and electric stimulation) or well-known methods (pulse oximetry and laser Doppler flowmetry) were excluded. Reviewers independently screened articles and extracted data. A patent search was also performed. RESULTS: Of 3062 studies, 65 were included that described nontraditional approaches for assessing pulp vitality. These included a range of optical diagnostic methods, ultrasound Doppler flowmetry (UDF), magnetic resonance imaging (MRI), terahertz imaging, tooth temperature measurements, as well as invasive methodologies, including 133xenon washout, radioisotope-labelled tracers, hydrogen gas desaturation, intravital microscopy and fluorescent microspheres isotope clearance. The patent search included artificial intelligence and biomarkers methods. CONCLUSIONS: This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios.

Simulated Hydrostatic Pulpal Pressure Effect on Microleakage-An Initial Study.

PURPOSE: This study's purpose was to evaluate the effect of simulated in vitro hydrostatic pulpal pressure (HPP) on microleakage. METHODS AND MATERIALS: Extracted third molars (n=12) were sectioned 5 mm below the cementoenamel junction, pulp tissue removed, and the sectioned crowns mounted on a Plexiglas plate penetrated by an 18-gauge stainless steel tube. The mounted specimen mesial surface received a 2×4×6 mm Class V preparation followed by restoration with a strongly acidic, one-step dental adhesive and a flowable microfilled resin, following all manufacturers' instructions. Restorations were finished to contour, and tubing was attached to a 20-cm elevated, 0.2% rhodamine G reservoir to the specimen steel tube for 48 hours. Specimens then received a nail polish coating to within 1 mm of the restoration margins and were placed in 2% methylene blue (MB) dye for 24 hours, followed by rinsing, embedding in epoxy resin, and sectioning into 1 mm slices using a diamond saw. Controls were intact molars (n=12) processed as above but without HPP. Specimen slices were evaluated using laser confocal microscopy with images exported to ImageJ software with microleakage assessed as the MB linear penetration as a percentage of the total interfacial wall length. Mean values were evaluated with the Kruskal Wallis/Dunn test at a 95% confidence level. RESULTS: The control specimens demonstrated significantly greater (p<0.0001) MB penetration than experimental specimens with simulated HPP. Under this study's conditions, simulated HPP significantly decreased MB dye penetration. CONCLUSION: Studies accomplished without simulated HPP may overestimate microleakage results.

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).

Effect of Orthognathic Surgery On Pulp Blood Flow and Pulp Sensibility: A Prospective Control Trial.

INTRODUCTION: Orthognathic surgery has the potential to compromise the vitality of the teeth. This paper aims to assess changes in pulp blood flow (PBF) and pulp sensibility (PS) of the anterior dentition following orthognathic surgery and to assess the influence of the proximity of the surgical osteotomy on the PBF and/or PS. METHODS: Twenty-six patients undergoing orthognathic surgery (Le Fort I or bilateral sagittal split osteotomy [BSSO]) were compared to sixteen control patients treated by fixed appliances only using Laser Doppler flowmeter (LDF) and thermal testing (CO2 snow). Surgery patients were tested at T1 (presurgery), T2 (4-5 weeks postsurgery), T3 (3 months postsurgery), and T4 (6 months postsurgery). Control patients were tested at T1 (pretreatment), T2 (6 months posttreatment), T3 (12 months posttreatment), and T4 (18 months posttreatment). Differences between the maxilla and mandible were assessed. RESULTS: No differences in PBF or PS were recorded in the control group. In the surgery group, both jaws followed the same pattern after surgery, an initial decrease at T2 followed by a gradual recovery to pretreatment PBF levels with no significant difference between T1 versus T4 in both jaws. No difference in PBF was observed between the maxilla and mandible at any testing time interval. CONCLUSIONS AND CLINICAL IMPLICATIONS: PBF and PS of the anterior dentition was severely affected immediately postsurgery, followed by a gradual increase to full recovery. This pattern of recovery was exhibited in both jaws. A negative sensibility response or discoloration should not be seen as an indication of irreversible ischemic pulp changes. Monitoring for at least 6 months or using LDF as a confirmatory test is required before any irreversible endodontic treatment is to be considered.

Stem cells in regenerative dentistry: Current understanding and future directions.

BACKGROUND: Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications. HIGHLIGHTS: To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency. CONCLUSION: Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions.

RvE1 Promotes Axin2+ Cell Regeneration and Reduces Bacterial Invasion.

Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an Axin2Cre-Dox;Ai14 genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato+ cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato+ cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases.

Approaches to vital pulp therapies.

Tooth decay, which leads to pulpal inflammation due to the pulp's response to bacterial components and byproducts is the most common infectious disease. The main goals of clinical management are to eliminate sources of infection, to facilitate healing by regulating inflammation indental tissue, and to replace lost tissues. A variety of novel approaches from tissue engineering based on stem cells, bioactive molecules, and extracellular matrix-like scaffold structures to therapeutic applications, or a combination of all these are present in the literature. Shortcomings of existing conventional materials for pulp capping and the novel approches aiming to preserve pulp vitality highligted the need for developing new targeted dental materials. This review looks at the novel approches for vital pulp treatments after briefly addresing the conventional vital pulp treatment as well as the regenerative and self defense capabilities of the pulp. A narrative review focusing on the current and future approaches for pulp preservation was performed after surveying the relevant papers on vital pulp therapies including pulp capping, pulpotomy, and potential approaches for facilitating dentin-pulp complex regeneration in PubMed, Medline, and Scopus databases.

In vitro, ex vivo, and in vivo models for dental pulp regeneration.

Based on the concept of tissue engineering (Cells-Scaffold-Bioactive molecules), regenerative endodontics appeared as a new notion for dental endodontic treatment. Its approaches aim to preserve dental pulp vitality (pulp capping) or to regenerate a vascularized pulp-like tissue inside necrotic root canals by cell homing. To improve the methods of tissue engineering for pulp regeneration, numerous studies using in vitro, ex vivo, and in vivo models have been performed. This review explores the evolution of laboratory models used in such studies and classifies them according to different criteria. It starts from the initial two-dimensional in vitro models that allowed characterization of stem cell behavior, through 3D culture matrices combined with dental tissue and finally arrives at the more challenging ex vivo and in vivo models. The travel which follows the elaboration of such models reveals the difficulty in establishing reproducible laboratory models for dental pulp regeneration. The development of well-established protocols and new laboratory ex vivo and in vivo models in the field of pulp regeneration would lead to consistent results, reduction of animal experimentation, and facilitation of the translation to clinical practice.

The effect of intentionally perforating the floor of the pulp chamber on pulpal healing after tooth replantation in mice.

OBJECTIVES: Shortening the root of a mouse molar prior to tooth replantation results in early revascularization in the pulp cavity and activation of the dental pulp quiescent stem cells. This study aimed to validate the effects of pulp chamber floor perforation on pulpal healing after tooth replantation as a strategy to promote early revascularization into the pulp. METHODS: The maxillary first molars of three-week-old Crlj:CD1 mice were extracted and repositioned into the original socket: the left teeth were immediately replanted (control group: CG), whereas the floor of the pulp chamber of the right teeth was perforated with a tungsten carbide bur before tooth replantation (experimental group: EG). The samples were collected from three days to eight weeks postoperatively. In addition to the TUNEL assay, immunohistochemistry for Nestin, CK14, and Ki-67 was conducted. RESULTS: In the EG, early revascularization occurred with a decrease in apoptosis and an increase in cell proliferation, facilitating pulpal healing, compared with the CG. The rate of Nestin-positive perimeter in the distal root significantly increased on days 5 and 14 and the amount of Nestin-positive hard tissue increased on day 14. However, on day 7, the number of epithelial cell rests of Malassez in the EG significantly decreased, making the EG susceptible to ankylosis at the floor. CONCLUSIONS: Intentionally perforating the floor of the pulp chamber provides a route for early revascularization, resulting in better pulpal healing after tooth replantation.

Pulp Regenerative Cell Therapy for Mature Molars: A Report of 2 Cases.

Regenerative cell therapy using autologous dental pulp stem cells (DPSCs) in mature single-rooted teeth is a potential alternative to traditional endodontic treatment. However, there is no evidence supporting the use of DPSCs in multirooted teeth. This case report aimed to demonstrate the feasibility and outcomes of pulp regenerative cell therapy in mature multirooted molars, which typically have a higher prevalence of apical deltas. A 26-year-old male and a 29-year-old male were referred for the pulp regeneration of their maxillary molars. After access preparation and establishing apical patency, root canal preparation and disinfection were performed. Autologous DPSCs were isolated from extracted third molars, cultured according to the guidelines of good manufacturing practice, and transplanted into the prepared root canals with granulocyte colony-stimulating factor in atelocollagen. The access cavity was sealed with Biodentine and composite resin. Clinical evaluation during the follow-up period of 48 weeks and laboratory evaluation after 4 weeks revealed no adverse events or evidence of systemic toxicity. After 48 weeks, radiographs and cone-beam computed tomography showed no periapical radiolucency. The teeth showed a positive response to electric pulp testing in 4 weeks in both cases. The signal intensities on magnetic resonance imaging of the regenerated pulp tissue in the affected teeth were comparable to those of the normal pulp in adjacent teeth after 24 weeks. This report of 2 cases demonstrates the utility of DPSCs and the feasibility of pulp regenerative cell therapy in multirooted molars.

Células madre en odontología: nuevas perspectivas / Stem cells in dentistry: new perspectives

En el campo de la odontología, prevalecen actualmente alternativas terapéuticas con una filosofía conservadora. Sin embargo, con el advenimiento de los tratamientos con células madre (CM), se amplían las posibilidades terapéuticas, que buscan la combinación y el equilibrio entre la intervención tradicional y las posibilidades de reposición de estructuras anatómicas dañadas, a través de la regeneración de tejidos utilizando células madre o sus derivados (AU)

In the dentistry field, therapeutic alternatives with a conservative philosophy currently prevail. However, with the advent of stem cell (SC) treatments, therapeutic possibilities are expanding, seeking a combination and balance between traditional intervention and the pos- sibility of replacing damaged anatomical structures through tissue regeneration, using stem cells or their derivatives (AU)

Dental Pulp Fibroblast: A Star Cell.

INTRODUCTION: Dental pulp fibroblasts (DPFs) are the most abundant cell type in the dental pulp. They play pivotal roles; however, they are often mistaken to be involved only in the repair and maintenance of this connective tissue. METHODS: We used the search terms "pulp fibroblast," "complement system proteins," "pulp inflammation," "angiogenesis," and "dentin pulp regeneration" to identify articles from the PubMed and Scopus databases. RESULTS: These sentinel cells produce all complement system proteins participating in defense processes, control of inflammation, and dentin-pulp regeneration; produce several proinflammatory cytokines and chemokines and express pattern-recognition receptors, demonstrating their involvement in immunoregulatory mechanisms; express neuropeptides and their receptors, playing an important role in neurogenic inflammation and dental pulp wound healing; secrete angiogenic growth factors as well as neurotrophic proteins, essential for dentin-pulp regeneration; regulate neuronal plasticity processes; and can sense the external environment. CONCLUSIONS: This review highlights that DPFs are more than mere passive cells in pulp biology and presents an integrative analysis of their roles and functions.