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Biomolecules Feb 2022The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue... (Review)
Review
The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue regeneration in orthotopic and ectopic animal studies. A search strategy was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in the MEDLINE/PubMed database. Animal studies evaluating the application of signaling molecules to pulpectomized teeth for pulp tissue or dentin-pulp complex regeneration were included. From 2530 identified records, 18 fulfilled the eligibility criteria and were subjected to detailed qualitative analysis. Among the applied molecules, basic fibroblast growth factor, vascular endothelial growth factor, bone morphogenetic factor-7, nerve growth factor, and platelet-derived growth factor were the most frequently studied. The clinical, radiographical and histological outcome measures included healing of periapical lesions, root development, and apical closure, cellular recolonization of the pulp space, ingrowth of pulp-like connective tissue (vascularization and innervation), mineralized dentin-like tissue formation along the internal dentin walls, and odontoblast-like cells in contact with the internal dentin walls. The results indicate that signaling molecules play an important role in dentin/pulp regeneration. However, further studies are needed to determine a more specific subset combination of molecules to achieve greater efficiency towards the desired tissue engineering applications.
Topics: Animals; Dental Pulp; Dentin; Regeneration; Tissue Engineering; Vascular Endothelial Growth Factor A
PubMed: 35204786
DOI: 10.3390/biom12020285 -
Clinical Oral Investigations Apr 2021This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues. (Review)
Review
OBJECTIVE
This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues.
MATERIALS AND METHODS
A systematic search was carried out on the PubMed electronic platform using the following key terms: Ti "OR" titanium "AND" dental implants "AND" nanoparticles "OR" nano-scale debris "OR" nanometric debris "AND" osteoblasts "OR "cytotoxicity" OR "macrophage" OR "mutagenic" OR "peri-implantitis". The inclusion criteria involved articles published in the English language, until December 26, 2020, reporting the effect of nano-scale titanium particles as released from dental implants on the toxicity and damage of osteoblasts.
RESULTS
Of 258 articles identified, 14 articles were selected for this integrative review. Submicron and nano-scale cp Ti particles altered the behavior of cells in culture medium. An inflammatory response was triggered by macrophages, fibroblasts, osteoblasts, mesenchymal cells, and odontoblasts as indicated by the detection of several inflammatory mediators such as IL-6, IL-1β, TNF-α, and PGE2. The formation of a bioactive complex composed of calcium and phosphorus on titanium nanoparticles allowed their binding to proteins leading to the cell internalization phenomenon. The nanoparticles induced mutagenic and carcinogenic effects into the cells.
CONCLUSIONS
The cytotoxic effect of debris released from dental implants depends on the size, concentration, and chemical composition of the particles. A high concentration of particles on nanometric scale intensifies the inflammatory responses with mutagenic potential of the surrounding cells.
CLINICAL RELEVANCE
Titanium ions and debris have been detected in peri-implant tissues with different size, concentration, and forms. The presence of metallic debris at peri-implant tissues also stimulates the migration of immune cells and inflammatory reactions. Cp Ti and TiO micro- and nano-scale particles can reach the bloodstream, accumulating in lungs, liver, spleen, and bone marrow.
Topics: Dental Implants; Humans; Macrophages; Osteoblasts; Peri-Implantitis; Titanium
PubMed: 33616805
DOI: 10.1007/s00784-021-03785-z -
Materials (Basel, Switzerland) Dec 2022The main objective of this systematic review was to compare the apical healing, root maturation and histological characteristics of teeth treated with cell-based versus... (Review)
Review
BACKGROUND
The main objective of this systematic review was to compare the apical healing, root maturation and histological characteristics of teeth treated with cell-based versus cell-free techniques.
METHODS
The methodology of this review was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search strategy was carried out on PubMed, EMBASE and the Web of Science databases. The last search was done on 1 August 2021. Articles written in languages other than English were excluded. Two researchers independently selected the studies and extracted the data. As no randomized clinical trials were available, animal studies were included.
RESULTS
In total, 26 studies were included in the systematic review: 22 articles only researched the cell-free technique, 3 articles compared the cell-based to the cell-free technique, and 1 article compared the cell-based technique to apexification. In terms of apical healing, qualitative analysis of the data suggested that there seems to be no significant difference between cell-free and cell-based techniques. The results regarding tooth maturation are contradictory. The main difference between the cell-free and the cell-based techniques seems to be the histology of the treated tooth. The cell-free technique seems to result in cementum-like, bone-like or periodontal ligament-like tissue. One study, on the other hand, found that the cell-based technique resulted in regeneration of the whole pulp with an odontoblast layer, connective tissue, blood vessels and neuronal tissue.
CONCLUSIONS
Currently, the number of randomized clinical trials on this topic are very scarce. This is probably due to the limited infrastructure and lack of resources to apply the cell-based technique. Even though both techniques seem to be promising for clinical application, long-term data need to be provided regarding the healing and reparative patterns.
PubMed: 36500098
DOI: 10.3390/ma15238603 -
Progress in Biomaterials Dec 2018Infection of the dental pulp will result in inflammation and eventually tissue necrosis which is treated conventionally by pulpectomy and root canal treatment. Advances... (Review)
Review
Infection of the dental pulp will result in inflammation and eventually tissue necrosis which is treated conventionally by pulpectomy and root canal treatment. Advances in regenerative medicine and tissue engineering along with the introduction of new sources of stem cells have led to the possibility of pulp tissue regeneration. This systematic review analyzes animal studies published since 2010 to determine the ability of stem cell therapy to regenerate the dentine-pulp complex (DPC) and the success of clinical protocols. In vitro and human clinical studies are excluded and only the experimental studies on animal models were included. Dental pulp stem cells constitute the most commonly used cell type. The majority of stem cells are incorporated into various types of scaffold and implanted into root canals. Some of the studies combine growth factors with stem cells in an attempt to improve the outcome. Studies of ectopic transplantation using small animal models are simple and non-systematic evaluation techniques. Stem cell concentrations have not been so far reported; therefore, the translational value of such animal studies remains questionable. Though all types of stem cells appear capable of regenerating a dentine-pulp complex, still several factors have been considered in selecting the cell type. Co-administrative factors are essential for inducing the systemic migration of stem cells, and their vascularization and differentiation into odontoblast-like cells. Scaffolds provide a biodegradable structure able to control the release of growth factors. To identify problems and reduce costs, novel strategies should be initially tested in subcutaneous or renal capsule implantation followed by root canal models to confirm results.
PubMed: 30267369
DOI: 10.1007/s40204-018-0100-7 -
Annals of Anatomy = Anatomischer... May 2021Extracellular matrix molecules (ECMM) expression during tertiary dentinogenesis provides useful information for regenerative applications and efficacy of pulp capping... (Review)
Review
BACKGROUND
Extracellular matrix molecules (ECMM) expression during tertiary dentinogenesis provides useful information for regenerative applications and efficacy of pulp capping materials.
AIM
To identify and review the expression and roles of non-collagenous ECMM after successful direct pulp capping (DPC), following mechanical pulp exposures, via immunohistochemistry (IHC). The study addressed the question of where will successful DPC impact the IHC expression of these molecules.
DATA SOURCES
In vivo animal and human original clinical studies reporting on ECMM in relation to different follow-up periods were screened and evaluated via descriptive analysis. The electronic literature search was carried out in three databases (MEDLINE/PubMed, Web of Science, Scopus), followed by manual screening of relevant journals and cross-referencing, up to December 2018.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Randomized and non-randomized controlled trials, conducted in humans and animals, were selected. Histological evidence for tertiary dentine formation was a prerequisite for IHC evaluation.
STUDY APPRAISAL AND SYNTHESIS METHODS
The methodological quality of the included articles was independently assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) and the Cochrane risk of bias tool (RoB 1), respectively.
RESULTS
From a total of 1534 identified studies, 18 were included. Thirteen papers evaluated animal subjects and five studies were carried out on humans. In animals and humans, fibronectin and tenascin expressions were detected in pulp and odontoblast-like cells (OLC); dentine sialoprotein was expressed in both soft and newly-formed mineralized tissue. In animals, bone sialoprotein was early expressed, in association with OLC and predentin; the immunoreactivity for dentine sialophosphoprotein and dentine matrix protein-1 was associated with the OLC and dentine bridge; osteopontin was expressed in OLC, predentine and reparative dentine. A considerable heterogeneity was found in the methodologies of the included studies, as well as interspecies variability of results in terms of time.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Within the limited scientific evidence, all non-collagenous ECMM expressions during tertiary dentinogenesis are active and related to soft and hard tissues. There is a shortage of human studies, and future research directions should focus more on them. PROSPERO Protocol: CRD42019121304.
Topics: Animals; Dental Pulp; Dental Pulp Capping; Dentin, Secondary; Dentinogenesis; Extracellular Matrix; Humans; Odontoblasts
PubMed: 33400977
DOI: 10.1016/j.aanat.2020.151674 -
Journal of Dentistry Apr 2022This study aims to review systematically the dental pulp response to silver diamine fluoride (SDF) treatment, including the inflammatory response, pulp cells activity,... (Review)
Review
OBJECTIVE
This study aims to review systematically the dental pulp response to silver diamine fluoride (SDF) treatment, including the inflammatory response, pulp cells activity, dentinogenesis, silver penetration, and the presence of the bacteria in the dental pulp.
DATA
In vitro studies, animal studies, clinical studies, and case reports on the use of SDF on vital dental pulp were included. Quality assessment of the included studies was conducted. A narrative synthesis of the collected data was performed.
SOURCES
A systematic search was performed in ProQuest, PubMed, SCOPUS, and Web of Science databases for articles published from inception to Nov 1, 2021.
STUDY SELECTION
The initial search identified 1,433 publications, of which five publications met the inclusion criteria. These five publications reported the effect of direct/ indirect SDF application on the vital pulp of a total of 30 teeth. Direct SDF application on vital pulp caused pulp necrosis. Indirect SDF application caused none or mild inflammatory response of dental pulp. The odontoblasts in the dental pulp showed increased cellular activity. Tertiary dentine was formed in the pulpal side of the cavity with indirect SDF application. Accentuated incremental lines of tertiary dentine reflected disturbances in mineralisation. Silver ions were found to penetrate along the dentinal tubules but were not detected inside the pulp.
CONCLUSION
According to the limited available literature, direct SDF application causes pulp necrosis. Indirect SDF application is generally biocompatible to dental pulp tissue with a mild inflammatory response, increased odontoblastic activity, and increased tertiary dentine formation. Future studies with precise quantitative and qualitative tests, larger sample size and longer follow-up time are imperative to understand the biological activity of dental pulp to SDF treatment.
Topics: Animals; Dental Caries; Dental Pulp; Dental Pulp Necrosis; Dentin, Secondary; Fluorides, Topical; Quaternary Ammonium Compounds; Silver Compounds
PubMed: 35139409
DOI: 10.1016/j.jdent.2022.104066 -
Tissue Engineering. Part C, Methods Mar 2022Tooth loss leads to several oral problems and although a large number of treatments have been proposed to rehabilitate partially or totally edentulous patients, none of...
Tooth loss leads to several oral problems and although a large number of treatments have been proposed to rehabilitate partially or totally edentulous patients, none of them is based on replacement of a missing tooth by a new natural whole tooth. In the field of tissue engineering, some animal models have been developed to regenerate a natural tooth in the oral cavity. This review shows the state of the art in whole tooth regeneration based on data from studies. A systematic scoping review was conducted to evaluate studies that described whole-tooth regeneration and eruption in the oral cavity. The data demonstrated that over 100 animals were used in experimental studies and all of them received implants of tooth germs constructed by bioengineering processes. Mini pigs and pigs were used in four studies followed by mice ( = 1) and dog ( = 1). Over 58 (44%) animals showed whole tooth eruption around 3.5 months after tooth germ implantation (1 to 13.5 months). Most of specimens revealed the presence of odontoblasts, dentin, dentinal tubules, dental pulp, root analogue, cementum, blood vessels, and alveolar bone. It could be concluded that whole tooth regeneration was proved to be possible, but the challenge to overcome translational barriers and test these approaches in humans still remains. Impact Statement Advances in tissue engineering have led to the development of new methods to regenerate and replace tissues and organs, including teeth. Tooth regeneration is the main goal for the replacement of tooth loss and therefore current evidence showed that tissue engineering might provide this treatment in future.
Topics: Animals; Dental Pulp; Dogs; Humans; Mice; Swine; Swine, Miniature; Tissue Engineering; Tooth; Tooth Loss
PubMed: 35172636
DOI: 10.1089/ten.TEC.2022.0022 -
Biomaterial Investigations in Dentistry Dec 2020The significance of dental materials in dentin-pulp complex tissue engineering is undeniable. The mechanical properties and bioactivity of mineral trioxide aggregate... (Review)
Review
The significance of dental materials in dentin-pulp complex tissue engineering is undeniable. The mechanical properties and bioactivity of mineral trioxide aggregate (MTA) make it a promising biomaterial for future stem cell-based endodontic therapies. There are numerous studies suggesting the low cytotoxicity of MTA towards various types of cells. Moreover, it has been shown that MTA can enhance mesenchymal stem cells' (MSCs) osteo/odontogenic ability. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), a literature review was conducted in the Medline, PubMed, and Scopus databases. Among the identified records, the cytotoxicity and osteo/odontoblastic potential of MTA or its extract on stem cells were investigated. Previous studies have discovered the differentiation-inducing potential of MTA on MSCs, providing a background for dentin-pulp complex cell therapies using the MTA, however, animal trials are needed before moving into clinical trials. In conclusion, MTA can be a promising candidate dental biomaterial for futuristic stem cell-based endodontic therapies.
PubMed: 33313519
DOI: 10.1080/26415275.2020.1848432 -
Journal of Endodontics Dec 2016The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different... (Review)
Review
INTRODUCTION
The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different variants of tricalcium silicate cements (TSCs).
METHODS
A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing any cell type except dental pulp stem cells and any variant of tricalcium silicate cement either as the experimental or as the control group were included.
RESULTS
A total of 41 relevant articles were included in this review. Among the included studies, ProRoot MTA (Dentsply, Tulsa, OK) was the most commonly studied (69.1%) TSC variant, and 11 cell types were identified, with 13 articles investigating gene expression in osteoblasts. A total of 39 different genes/molecules expressed were found in the selected studies. The experimental group (irrespective of the TSC variant) was identified to express significantly increased gene expression compared with the control group (untreated) in all included studies. Recent studies have provided useful insight into the gene expression and molecular signaling of various cells in response to TSCs, and new elements have been supplied on the pathways activated in this process.
CONCLUSIONS
TSCs are capable of eliciting a favorable cellular response in periapical regeneration.
Topics: Calcium Compounds; Cell Line; Cell Proliferation; Cytokines; Dental Cements; Dental Cementum; Dental Materials; Dental Pulp; Fibroblasts; Gene Expression; Gene Expression Profiling; Humans; Materials Testing; Odontoblasts; Osteoblasts; Osteoclasts; Signal Transduction; Silicate Cement; Silicates; Stem Cells
PubMed: 27776883
DOI: 10.1016/j.joen.2016.08.027 -
International Endodontic Journal Jun 2016Stem cell-based therapy (SC-BT) is emerging as an alternative for endodontic therapies. The interaction between stem cells and scaffolds plays a crucial role in the... (Review)
Review
Stem cell-based therapy (SC-BT) is emerging as an alternative for endodontic therapies. The interaction between stem cells and scaffolds plays a crucial role in the generation of a 'friendly cell' microenvironment. The aim of this systematic review was to explore techniques applied to regenerate the pulp-dentine complex tissue using SC-BT. An electronic search into the SciVerse Scopus (SS), ISI Web Science (IWS) and Entrez PubMed (EP) using specific keywords was performed. Specific inclusion and exclusion criteria were predetermined. The search yielded papers, out of which full-text papers were included in the final analyses. Data extraction pooled the results in four main topics: (a) influence of the chemical properties of the scaffolds over cell behaviour; (b) influence of the physical characteristics of scaffolds over cell behaviour; (c) strategies applied to improve the stem cell/scaffold interface; and (d) influence of cue microenvironment on stem cell differentiation towards odontoblast-like cells and pulp-like tissue formation. The relationship between the scaffolds, the environment and the growth factors released from dentine are critical for de novo pulp tissue regeneration. The preconditioning of dentine walls with ethylenediaminetetraacetic acid (EDTA) was imperative for successful pulp-dentine complex regeneration. An analyses of the grouped results revealed that pulp regeneration was an attainable goal.
Topics: Dental Pulp; Guided Tissue Regeneration; Humans; Stem Cell Transplantation; Tissue Engineering; Tissue Scaffolds
PubMed: 26101143
DOI: 10.1111/iej.12489