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International Endodontic Journal Apr 2018The typical treatment for irreversibly inflamed/necrotic pulp tissue is root canal treatment. As an alternative approach, regenerative endodontics aims to regenerate... (Review)
Review
The typical treatment for irreversibly inflamed/necrotic pulp tissue is root canal treatment. As an alternative approach, regenerative endodontics aims to regenerate dental pulp-like tissues using two possible strategies: cell transplantation and cell homing. The former requires exogenously transplanted stem cells, complex procedures and high costs; the latter employs the host's endogenous cells to achieve tissue repair/regeneration, which is more clinically translatable. This systematic review examines cell homing for dental pulp regeneration, selecting articles on in vitro experiments, in vivo ectopic transplantation models and in situ pulp revascularization. MEDLINE/PubMed and Scopus databases were electronically searched for articles without limits in publication date. Two reviewers independently screened and included papers according to the predefined selection criteria. The electronic searches identified 46 studies. After title, abstract and full-text examination, 10 articles met the inclusion criteria. In vitro data highlighted that multiple cytokines have the capacity to induce migration, proliferation and differentiation of dental pulp stem/progenitor cells. The majority of the in vivo studies obtained regenerated connective pulp-like tissues with neovascularization. In some cases, the samples showed new innervation and new dentine deposition. The in situ pulp revascularization regenerated intracanal pulp-like tissues with neovascularization, innervation and dentine formation. Cell homing strategies for pulp regeneration need further understanding and improvement if they are to become a reliable and effective approach in endodontics. Nevertheless, cell homing currently represents the most clinically viable pathway for dental pulp regeneration.
Topics: Cell Differentiation; Cell Movement; Cell Proliferation; Databases, Factual; Dental Pulp; Endodontics; Humans; Regeneration; Root Canal Therapy; Stem Cell Transplantation; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 29047120
DOI: 10.1111/iej.12868 -
Dental Materials : Official Publication... Apr 2023The current standard for treating irreversibly damaged dental pulp is root canal therapy, which involves complete removal and debridement of the pulp space and filling... (Review)
Review
OBJECTIVES
The current standard for treating irreversibly damaged dental pulp is root canal therapy, which involves complete removal and debridement of the pulp space and filling with an inert biomaterial. A regenerative approach to treating diseased dental pulp may allow for complete healing of the native tooth structure and enhance the long-term outcome of once-necrotic teeth. The aim of this paper is, therefore, to highlight the current state of dental pulp tissue engineering and immunomodulatory biomaterials properties, identifying exciting opportunities for their synergy in developing next-generation biomaterials-driven technologies.
METHODS
An overview of the inflammatory process focusing on immune responses of the dental pulp, followed by periapical and periodontal tissue inflammation are elaborated. Then, the most recent advances in treating infection-induced inflammatory oral diseases, focusing on biocompatible materials with immunomodulatory properties are discussed. Of note, we highlight some of the most used modifications in biomaterials' surface, or content/drug incorporation focused on immunomodulation based on an extensive literature search over the last decade.
RESULTS
We provide the readers with a critical summary of recent advances in immunomodulation related to pulpal, periapical, and periodontal diseases while bringing light to tissue engineering strategies focusing on healing and regenerating multiple tissue types.
SIGNIFICANCE
Significant advances have been made in developing biomaterials that take advantage of the host's immune system to guide a specific regenerative outcome. Biomaterials that efficiently and predictably modulate cells in the dental pulp complex hold significant clinical promise for improving standards of care compared to endodontic root canal therapy.
Topics: Biocompatible Materials; Dental Pulp; Tissue Engineering; Root Canal Therapy; Regeneration
PubMed: 36894414
DOI: 10.1016/j.dental.2023.03.013 -
Oral Diseases Mar 2018The dentin-pulp complex is a highly specialized tissue for protecting the dental pulp. Odontoblasts are long-lived, hard-tissue-forming cells in the dentin-pulp complex... (Review)
Review
The dentin-pulp complex is a highly specialized tissue for protecting the dental pulp. Odontoblasts are long-lived, hard-tissue-forming cells in the dentin-pulp complex and critically involved in inflammatory responses against invading pathogens. Autophagy is a highly conserved homeostasis mechanism of living cells under various stress conditions. Growing evidence in the literature addresses the role of autophagy in odontoblast differentiation and aging. This review summarizes the current knowledge about autophagy for the dentin-pulp complex in resisting inflammation.
Topics: Autophagy; Cell Differentiation; Dental Pulp; Dentin; Humans; Inflammation; Odontoblasts
PubMed: 29480617
DOI: 10.1111/odi.12749 -
Journal of Endodontics Sep 2017Dental pulp regeneration after pulp necrosis in immature teeth represents a major departure from traditional endodontic therapy of these conditions. Preliminary clinical... (Review)
Review
Dental pulp regeneration after pulp necrosis in immature teeth represents a major departure from traditional endodontic therapy of these conditions. Preliminary clinical attempts have shown the feasibility of developing mineralized repair tissue, which may provide a clinically acceptable outcome. However, this outcome may not provide sufficient host response and root strength to ensure the longevity of the involved teeth. It is not clear if these preliminary suboptimal results are caused by the inability to fully disinfect the pulp space or the absence of a suitable progenitor cell/scaffold template together with adequate vascularity. Moreover, it is not known to what degree the root canal system needs to be disinfected in order for clinical success to be evident. This article describes the current clinical strategies and protocols for the optimal disinfection and preparation of the pulp space environment to promote periapical healing as well as soft and hard tissue development after an infectious process. Current and future strategies for disinfecting the pulp space with minimal disruption of the necessary biological factors from dentin, the progenitor cells in periapical vital tissues, and the vascularity are discussed. The potential for success of pulp regeneration after necrosis and infection would transform the practice of endodontics, even for mature teeth. This is a goal worth pursuing because it would achieve the restoration of normal host responses in the pulp space and the regeneration of destroyed dental tissues.
Topics: Anti-Bacterial Agents; Bacteria; Dental Pulp; Disinfection; Humans; Regeneration; Stem Cells
PubMed: 28778502
DOI: 10.1016/j.joen.2017.06.010 -
Bio-medical Materials and Engineering 2017Tooth vitality and health are related to the presence of a living connective tissue, the dental pulp (DP), in the center of the dental organ. The DP contains the tooth... (Review)
Review
Tooth vitality and health are related to the presence of a living connective tissue, the dental pulp (DP), in the center of the dental organ. The DP contains the tooth immune defence system that is activated against invading oral cariogenic bacteria during the caries process and the tissue repair/regeneration machinery involved following microorganisms' eradication. However, penetration of oral bacteria into the DP often leads to complete tissue destruction and colonization of the endodontic space by microorganisms. Classical endodontic therapies consist of disinfecting then sealing the endodontic space with a gutta percha-based material. However, re-infections of the endodontic space by oral bacteria can occur, owing to the lack of tightness of the material. Recent findings suggest that regenerating a fully functional pulp tissue may be an ideal therapeutic solution to maintain a tooth defence system that will detect and help manage future injuries. The objective of this paper was to explain the different revascularization and regeneration strategies that have been proposed to reconstitute a living DP tissue and to discuss the main challenges that have to be resolved to improve these therapeutic strategies.
Topics: Angiogenesis Inducing Agents; Dental Pulp; Humans; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regeneration; Tissue Scaffolds; Tooth
PubMed: 28372291
DOI: 10.3233/BME-171637 -
Archives of Oral Biology Jan 2020Description of the odontoblast lifecycle, an overview of the known complex molecular interactions that occur when the health of the dental pulp is challenged and the... (Review)
Review
OBJECTIVE
Description of the odontoblast lifecycle, an overview of the known complex molecular interactions that occur when the health of the dental pulp is challenged and the current and future management strategies on vital and non-vital teeth.
METHODS
A literature search of the electronic databases included MEDLINE (1966-April 2019), CINAHL (1982-April 2019), EMBASE and EMBASE Classic (1947-April 2019), and hand searches of references retrieved were undertaken using the following MESH terms 'odontoblast*', 'inflammation', 'dental pulp*', 'wound healing' and 'regenerative medicine'.
RESULTS
Odontoblasts have a sensory and mechano-transduction role so as to detect external stimuli that challenge the dental pulp. On detection, odontoblasts stimulate the innate immunity by activating defence mechanisms key in the healing and repair mechanisms of the tooth. A better understanding of the role of odontoblasts within the dental pulp complex will allow an opportunity for biological management to remove the cause of the insult to the dental pulp, modulate the inflammatory process, and promote the healing and repair capabilities of the tooth. Current strategies include use of conventional dental pulp medicaments while newer methods include bioactive molecules, epigenetic modifications and tissue engineering.
CONCLUSION
Regenerative medicine methods are in their infancy and experimental stages at best. This review highlights the future direction of dental caries management and consequently research.
Topics: Dental Caries; Dental Pulp; Dental Pulp Exposure; Humans; Immunity, Innate; Odontoblasts; Regeneration
PubMed: 31710968
DOI: 10.1016/j.archoralbio.2019.104591 -
Archives of Oral Biology Mar 2019This short review summarizes our current knowledge about dental stem cell aging and about possible targets for the regulation of cellular senescence. (Review)
Review
OBJECTIVE
This short review summarizes our current knowledge about dental stem cell aging and about possible targets for the regulation of cellular senescence.
DESIGN
A literature search was performed using a combination of keywords, e.g., stem cells, replicative senescence, differentiation potential, dental pulp, dental follicle and periodontal ligament.
RESULTS
Previous studies have shown that cellular senescence occurs while the proliferation of dental stem cells. Moreover, the differentiation potential was significantly decreased in senescent stem cells and senescent cells secrete also factors that are harmful to the adjacent tissue cells. Moreover, many targets for the regulation of cellular senescence are considered; for example pathways related to the nutrient sensing such as the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway.
CONCLUSIONS
The regulation of cellular senescence will play a crucial role in the clinical use of stem cells. However, there is no cell culture protocol available that prevents dental stem cell senescence. Therefore, more knowledge about molecular processes in stem cells is needed before and after the induction of senescence.
Topics: AMP-Activated Protein Kinase Kinases; Aging; Cell Differentiation; Cell Proliferation; Cellular Senescence; Dental Pulp; Dental Sac; Nutrients; Odontogenesis; Protein Kinases; Stem Cells
PubMed: 30685471
DOI: 10.1016/j.archoralbio.2019.01.012 -
Cells Aug 2021The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an...
The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an immunological, cellular, and vascular reaction in an attempt to defend itself and resolve the affected tissue. The expression of different microRNAs during pulp inflammation has been previously documented. MicroRNAs (miRNAs) are endogenous small molecules involved in the transcription of genes that regulate the immune system and the inflammatory response. They are present in cellular and physiological functions, as well as in the pathogenesis of human diseases, becoming potential biomarkers for diagnosis, prognosis, monitoring, and safety. Previous studies have evidenced the different roles played by miRNAs in proinflammatory, anti-inflammatory, and immunological phenomena in the dental pulp, highlighting specific key functions of pulp pathology. This systematized review aims to provide an understanding of the role of the different microRNAs detected in the pulp and their effects on the expression of the different target genes that are involved during pulp inflammation.
Topics: Cell Differentiation; Dental Pulp; Down-Regulation; Gene Expression Regulation; Humans; Inflammation; MicroRNAs; RNA, Messenger; Signal Transduction; Up-Regulation
PubMed: 34440911
DOI: 10.3390/cells10082142 -
Romanian Journal of Morphology and... 2016Dental stem niches (DSNs) reside in different dental tissues, being of particular importance in tissue engineering and dental regeneration procedures. The present paper... (Review)
Review
Dental stem niches (DSNs) reside in different dental tissues, being of particular importance in tissue engineering and dental regeneration procedures. The present paper aims to review the DSNs from the view of niche inhabitants, either extrinsic, such as cells of the myeloid lineage, or intrinsic, such as endothelial cells, perivascular cells and spindle-shaped stromal cells, e.g., telocytes. DSNs harbor different dental stem÷progenitor cell morphologies, in different stages of differentiation and with various potentialities, the angiogenic potential with respect to regenerative endodontic procedures being emphasized here. It seems therefore important to consider the DSNs as being heterogeneous, for a better understanding of an accurate identification of niche team players in regenerative medicine.
Topics: Cell Differentiation; Dental Pulp; Humans; Phenotype; Stem Cell Niche
PubMed: 28174783
DOI: No ID Found -
Journal of Dental Research Feb 2017The pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls, with the apical foramina being the only access. The... (Review)
Review
The pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls, with the apical foramina being the only access. The pulp vascular system is not only responsible for nutrient supply and waste removal but also contributes actively to the pulp inflammatory response and subsequent regeneration. This review discusses the underlying mechanisms of pulp vascularization during tooth development, regeneration, and therapeutic procedures, such as tissue engineering and tooth transplantation. Whereas the pulp vascular system is established by vasculogenesis during embryonic development, sprouting angiogenesis is the predominant process during regeneration and therapeutic processes. Hypoxia can be considered a common driving force. Dental pulp cells under hypoxic stress release proangiogenic factors, with vascular endothelial growth factor being one of the most potent. The benefit of exogenous vascular endothelial growth factor application in tissue engineering has been well demonstrated. Interestingly, dental pulp stem cells have an important role in pulp revascularization. Indeed, recent studies show that dental pulp stem cell secretome possesses angiogenic potential that actively contributes to the angiogenic process by guiding endothelial cells and even by differentiating themselves into the endothelial lineage. Although considerable insight has been obtained in the processes underlying pulp vascularization, many questions remain relating to the signaling pathways, timing, and influence of various stress conditions.
Topics: Animals; Bone Regeneration; Dental Pulp; Humans; Neovascularization, Physiologic; Tissue Engineering; Tooth
PubMed: 28106505
DOI: 10.1177/0022034516671688