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Remineralization of Dentinal Lesions Using Biomimetic Agents: A Systematic Review and Meta-Analysis.Biomimetics (Basel, Switzerland) Apr 2023The objective of this article was to systematically provide an up-to-date review on the different methods of remineralizing human dentine using different biomimetic... (Review)
Review
The objective of this article was to systematically provide an up-to-date review on the different methods of remineralizing human dentine using different biomimetic agents. The authors performed a systematic search within PubMed, Scopus, and Web of Science in addition to the grey literature in Google Scholar using MeSH terms. The PICO question was P: human teeth dentinal sections; I: application of biomimetic remineralizing agents; C: other non-biomimetic approaches; O: extent of remineralization and physical properties of remineralized dentine. The initially identified studies were screened for titles and abstracts. Non-English articles, reviews, animal studies, studies involving the resin-dentine interface, and other irrelevant articles were then excluded. The other remaining full-text articles were retrieved. Bibliographies of the remaining articles were searched for relevant studies that could be included. A total of 4741 articles were found, and finally, 39 full-text articles were incorporated in the current systematic review. From these, twenty-six research studies used non-collagenous protein (NCP) analogs to biomineralize dentine, six studies used bioactive materials derived from natural sources, six studies used zinc hydroxyapatite, and one study used amelogenin peptide to induce hydroxyapatite formation on the surface of demineralized dentine. Additive effects of triclosan and epigenin were assessed when combined with commonly available NCPs. Overall, a moderate risk of bias was observed and, hence, the findings of the included studies could be acceptable. A meta-analysis of some similar studies was performed to assess the depth of remineralization and elastic modulus. Despite having high heterogeneity (I > 90), all the studies showed a significant improvement in biomimetic remineralization efficacy as compared to the control. All the included studies carried out a functional remineralization assessment and found a 90-98% efficacy in the extent of remineralization while the elastic modulus reached 88.78 ± 8.35 GPa, which is close to natural dentine. It is pertinent to note the limitations of these studies that have been carried out in vitro under controlled settings, which lack the effects of a natural oral environment. To conclude, the authors suggest that the biomimetic remineralization of dentine using NCP analogs, bioactive materials, and natural products carries significant potential in treating dentinal lesions; however, more long-term studies are needed to assess their clinical applications in vivo.
PubMed: 37092411
DOI: 10.3390/biomimetics8020159 -
International Journal of Environmental... Oct 2022The need to predict, diagnose and treat peri-implant diseases has never been greater. We present a systematic review of the literature on the changes in the expression... (Review)
Review
The need to predict, diagnose and treat peri-implant diseases has never been greater. We present a systematic review of the literature on the changes in the expression of biomarkers in peri-implant crevicular fluid (PICF) before and after treatment of peri-implantitis. Bacterial composition, clinical and radiographic parameters, and systemic biomarkers before and after treatment are reported as secondary outcomes. A total of 17 studies were included. Treatment groups were non-surgical treatment or surgical treatment, either alone or with adjunctive therapy. Our findings show that non-surgical treatment alone does not influence biomarker levels or clinical outcomes. Both adjunctive photodynamic therapy and local minocycline application resulted in a reduction of interleukin (IL)-1β and IL-10 twelve months after treatment. Non-surgical treatments with adjunctive use of lasers or antimicrobials were more effective at improving the clinical outcomes in the short-term only. Access flap debridement led to matrix metalloproteinase (MMP)-8 and tumour necrosis factor-α reduction twelve months post-surgery. Surgical debridement with adjunctive antimicrobials achieved a decrease in MMP-8 at three months. Adjunctive use of Emdogain (EMD) was associated with a reduction in 40 PICF proteins compared to access flap surgery alone. Surgical interventions were more effective at reducing probing pocket depth and bleeding on probing both in the short- and long-term. Surgical treatment in combination with EMD was found to be more effective in resolving inflammation up to twelve months.
Topics: Humans; Peri-Implantitis; Minocycline; Biomarkers; Debridement; Anti-Infective Agents
PubMed: 36360962
DOI: 10.3390/ijerph192114085 -
International Journal of Molecular... Aug 2021Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived... (Meta-Analysis)
Meta-Analysis
Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived peptides, named LRAP, TRAP, SP, and C11, in bone tissue engineering. Interestingly, these peptides seem to maintain or even improve the biological activity of the full-length protein, which has received attention in the field of bone regeneration. In this article, the authors combined a systematic and a narrative review. The former is focused on the existing scientific evidence on LRAP, TRAP, SP, and C11's ability to induce the production of mineralized extracellular matrix, while the latter is concentrated on the structure and function of amelogenin and amelogenin-derived peptides. Overall, the collected data suggest that LRAP and SP are able to induce stromal stem cell differentiation towards osteoblastic phenotypes; specifically, SP seems to be more reliable in bone regenerative approaches due to its osteoinduction and the absence of immunogenicity. However, even if some evidence is convincing, the limited number of studies and the scarcity of in vivo studies force us to wait for further investigations before drawing a solid final statement on the real potential of amelogenin-derived peptides in bone tissue engineering.
Topics: Amelogenin; Amino Acid Sequence; Animals; Biomarkers; Bone Regeneration; Cell Differentiation; Gene Expression Regulation; Humans; Immunohistochemistry; Peptides; Tissue Engineering; Translational Research, Biomedical
PubMed: 34502132
DOI: 10.3390/ijms22179224 -
Medicina Oral, Patologia Oral Y Cirugia... May 2020The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early...
BACKGROUND
The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis.
AIM
To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features.
MATERIAL AND METHODS
An electronic systematic review was performed up to September 2019 in multiple databases.
RESULTS
A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for amelogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm.
CONCLUSION
POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently.
Topics: Adolescent; Adult; Child; Child, Preschool; Epithelium; Humans; Male; Mandible; Neoplasm Recurrence, Local; Odontogenesis; Odontogenic Tumors; Young Adult
PubMed: 32040459
DOI: 10.4317/medoral.23432 -
Caries Research 2017Recent progress in the field of molecular biology and techniques of DNA sequence analysis allowed determining the meaning of hereditary factors of many common human... (Review)
Review
Recent progress in the field of molecular biology and techniques of DNA sequence analysis allowed determining the meaning of hereditary factors of many common human diseases. Studies of genetic mechanisms in the aetiology of caries encompass, primarily, 4 main groups of genes responsible for (1) the development of enamel, (2) formation and composition of saliva, (3) immunological responses, and (4) carbohydrate metabolism. The aim of this study was to present current knowledge about the influence of single nucleotide polymorphism (SNP) genetic variants on the occurrence of dental caries. PubMed/Medline, Embase, and Cochrane Library databases were searched for papers on the influence of genetic factors connected with SNP on the occurrence of dental caries in children, teenagers, and adults. Thirty original papers written in English were included in this review. Study groups ranged from 30 to 13,000 subjects. SNPs were observed in 30 genes. Results of the majority of studies confirm the participation of hereditary factors in the aetiology of caries. Three genes, AMELX, AQP5, and ESRRB, have the most promising evidence based on multiple replications and data, supporting a role of these genes in caries. The review of the literature proves that SNP is linked with the aetiology of dental caries.
Topics: Dental Caries; Humans; Polymorphism, Single Nucleotide
PubMed: 28668961
DOI: 10.1159/000476075 -
Journal of Clinical Periodontology Jul 2017In order to enhance clinical improvement of intrabony defects, the addition of enamel matrix derivatives (EMD) to bone substitues (BS) has been investigated. The aim of... (Meta-Analysis)
Meta-Analysis Review
AIM
In order to enhance clinical improvement of intrabony defects, the addition of enamel matrix derivatives (EMD) to bone substitues (BS) has been investigated. The aim of this systematic review is to figure out whether such a combination, in comparison to the treatment with BS alone has beneficial effects on the following outcomes: clinical attachment level (CAL) gain, probing depth (PD) reduction and recession (REC).
METHODS
Electronic databases (PUBMED, SCOPUS, EBSCO Host Research Databases and Web of Knowledge) were searched for randomized controlled trials in humans addressing the use of a combination of BS and EMD versus a control group with BS alone for the treatment of intrabony defects, with a minimum of 6 months of follow-up; meta-analysis and trial sequential analysis were then performed.
RESULTS
From a total of 1,197 records screened by title and abstract, nine studies were read full-text and five out of them included in the meta-analysis. No significant differences have been demonstrated both for CAL gain, PD reduction and REC between test and control groups.
CONCLUSIONS
In the treatment of intrabony defects, the addition of EMD to BS seems to be not beneficial in terms of CAL gain, PD reduction and REC changes. However, such results should be considered with caution because of the small number of studies included in the meta-analysis and their heterogeneity.
Topics: Alveolar Bone Loss; Bone Regeneration; Bone Substitutes; Combined Modality Therapy; Dental Enamel Proteins; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Periodontal Index
PubMed: 28477366
DOI: 10.1111/jcpe.12742 -
Journal of Clinical Periodontology Mar 2017Periodontal diseases and dental caries are the most common diseases of humans and the main cause of tooth loss. Both diseases can lead to nutritional compromise and...
Interaction of lifestyle, behaviour or systemic diseases with dental caries and periodontal diseases: consensus report of group 2 of the joint EFP/ORCA workshop on the boundaries between caries and periodontal diseases.
UNLABELLED
Periodontal diseases and dental caries are the most common diseases of humans and the main cause of tooth loss. Both diseases can lead to nutritional compromise and negative impacts upon self-esteem and quality of life. As complex chronic diseases, they share common risk factors, such as a requirement for a pathogenic plaque biofilm, yet they exhibit distinct pathophysiologies. Multiple exposures contribute to their causal pathways, and susceptibility involves risk factors that are inherited (e.g. genetic variants), and those that are acquired (e.g. socio-economic factors, biofilm load or composition, smoking, carbohydrate intake). Identification of these factors is crucial in the prevention of both diseases as well as in their management.
AIM
To systematically appraise the scientific literature to identify potential risk factors for caries and periodontal diseases.
METHODS
One systematic review (genetic risk factors), one narrative review (role of diet and nutrition) and reference documentation for modifiable acquired risk factors common to both disease groups, formed the basis of the report.
RESULTS & CONCLUSIONS
There is moderately strong evidence for a genetic contribution to periodontal diseases and caries susceptibility, with an attributable risk estimated to be up to 50%. The genetics literature for periodontal disease is more substantial than for caries and genes associated with chronic periodontitis are the vitamin D receptor (VDR), Fc gamma receptor IIA (Fc-γRIIA) and Interleukin 10 (IL10) genes. For caries, genes involved in enamel formation (AMELX, AMBN, ENAM, TUFT, MMP20, and KLK4), salivary characteristics (AQP5), immune regulation and dietary preferences had the largest impact. No common genetic variants were found. Fermentable carbohydrates (sugars and starches) were the most relevant common dietary risk factor for both diseases, but associated mechanisms differed. In caries, the fermentation process leads to acid production and the generation of biofilm components such as Glucans. In periodontitis, glycaemia drives oxidative stress and advanced glycation end-products may also trigger a hyper inflammatory state. Micronutrient deficiencies, such as for vitamin C, vitamin D or vitamin B12, may be related to the onset and progression of both diseases. Functional foods or probiotics could be helpful in caries prevention and periodontal disease management, although evidence is limited and biological mechanisms not fully elucidated. Hyposalivation, rheumatoid arthritis, smoking/tobacco use, undiagnosed or sub-optimally controlled diabetes and obesity are common acquired risk factors for both caries and periodontal diseases.
Topics: Dental Caries; Health Behavior; Humans; Life Style; Periodontal Diseases; Risk Factors
PubMed: 28266114
DOI: 10.1111/jcpe.12685 -
Journal of Clinical Periodontology Apr 2014To review the effectiveness of enamel matrix derivative (EMD) in the treatment of periodontal pockets of suprabony defects. (Meta-Analysis)
Meta-Analysis Review
Does enamel matrix derivative application provide additional clinical benefits in residual periodontal pockets associated with suprabony defects? A systematic review and meta-analysis of randomized clinical trials.
OBJECTIVE
To review the effectiveness of enamel matrix derivative (EMD) in the treatment of periodontal pockets of suprabony defects.
METHODS
Randomized Clinical Trials comparing open flap debridement (OFD) versus EMD in periodontal suprabony defects were identified through electronic and manual search. Screening, data extraction and quality assessment were conducted. The primary outcome measures were tooth survival (TS) and clinical attachment level (CAL) gain. Pocket probing depth (PPD) reduction and recession (REC) increase were secondary outcome measures. Information concerning clinical and radiological bone gain was also collected.
RESULTS
The search identified 1170 studies, three articles reporting on (99 subjects/358 teeth) met the inclusion criteria and were included. No tooth was lost during follow-up (8-12 months). The adjunctive mean benefit of EMD was: 1.2 mm for CAL gain [confidence interval (CI): (0.9, 1.4), p < 0.00001, I(2) = 66%], 1.2 mm for the PPD reduction (CI: [0.8, 1.5], p < 0.0001, I(2) = 0%), -0.5 mm for the REC increase (CI: [-0.8, -0.2], p = 0.003, I(2) = 0%). Potential risk of bias was identified.
CONCLUSIONS
No differences were noted in TS but EMD application resulted in clinical and radiographic additional benefits compared to OFD alone. Nevertheless, the paucity of data, the risk of methodological and potential publication bias suggests caution in interpreting these results while supporting multicenter studies for this specific application.
Topics: Alveolar Bone Loss; Dental Enamel Proteins; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Periodontal Pocket; Randomized Controlled Trials as Topic; Surgical Flaps; Tooth Loss; Treatment Outcome
PubMed: 24329867
DOI: 10.1111/jcpe.12218 -
The Cochrane Database of Systematic... Oct 2009Periodontitis is a chronic infective disease of the gums caused by bacteria present in dental plaque. This condition induces the breakdown of the tooth supporting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontitis is a chronic infective disease of the gums caused by bacteria present in dental plaque. This condition induces the breakdown of the tooth supporting apparatus until teeth are lost. Surgery may be indicated to arrest disease progression and regenerate lost tissues. Several surgical techniques have been developed to regenerate periodontal tissues including guided tissue regeneration (GTR), bone grafting (BG) and the use of enamel matrix derivative (EMD). EMD is an extract of enamel matrix and contains amelogenins of various molecular weights. Amelogenins are involved in the formation of enamel and periodontal attachment formation during tooth development.
OBJECTIVES
To test whether EMD is effective, and to compare EMD versus GTR, and various BG procedures for the treatment of intrabony defects.
SEARCH STRATEGY
We searched the Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE. Several journals were handsearched. No language restrictions were applied. Authors of randomised controlled trials (RCTs) identified, personal contacts and the manufacturer were contacted to identify unpublished trials. Most recent search: February 2009.
SELECTION CRITERIA
RCTs on patients affected by periodontitis having intrabony defects of at least 3 mm treated with EMD compared with open flap debridement, GTR and various BG procedures with at least 1 year follow up. The outcome measures considered were: tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), bone levels from the bottom of the defects on intraoral radiographs, aesthetics and adverse events. The following time-points were to be evaluated: 1, 5 and 10 years.
DATA COLLECTION AND ANALYSIS
Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two authors. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). It was decided not to investigate heterogeneity, but a sensitivity analysis for the risk of bias of the trials was performed.
MAIN RESULTS
Thirteen trials were included out of 35 potentially eligible trials. No included trial presented data after 5 years of follow up, therefore all data refer to the 1-year time point. A meta-analysis including nine trials showed that EMD treated sites displayed statistically significant PAL improvements (mean difference 1.1 mm, 95% CI 0.61 to 1.55) and PPD reduction (0.9 mm, 95% CI 0.44 to 1.31) when compared to placebo or control treated sites, though a high degree of heterogeneity was found. Significantly more sites had < 2 mm PAL gain in the control group, with RR 0.53 (95% CI 0.34 to 0.82). Approximately nine patients needed to be treated (NNT) to have one patient gaining 2 mm or more PAL over the control group, based on a prevalence in the control group of 25%. No differences in tooth loss or aesthetic appearance as judged by the patients were observed. When evaluating only trials at a low risk of bias in a sensitivity analysis (four trials), the effect size for PAL was 0.62 mm (95% CI 0.28 to 0.96), which was less than 1.1 mm for the overall result. Comparing EMD with GTR (five trials), GTR showed statistically significant more postoperative complications (three trials, RR 0.12, 95% CI 0.02 to 0.85) and more REC (0.4 mm 95% CI 0.15 to 0.66). The only trial comparing EMD with a bioactive ceramic filler found statistically significant more REC (-1.60 mm, 95% CI -2.74 to -0.46) at the EMG treated sites.
AUTHORS' CONCLUSIONS
One year after its application, EMD significantly improved PAL levels (1.1 mm) and PPD reduction (0.9 mm) when compared to a placebo or control, however, the high degree of heterogeneity observed among trials suggests that results have to be interpreted with great caution. In addition, a sensitivity analysis indicated that the overall treatment effect might be overestimated. The actual clinical advantages of using EMD are unknown. With the exception of significantly more postoperative complications in the GTR group, there was no evidence of clinically important differences between GTR and EMD. Bone substitutes may be associated with less REC than EMD.
Topics: Alveolar Bone Loss; Bone Regeneration; Bone Transplantation; Dental Enamel Proteins; Guided Tissue Regeneration, Periodontal; Humans; Randomized Controlled Trials as Topic
PubMed: 19821315
DOI: 10.1002/14651858.CD003875.pub3 -
European Journal of Oral Implantology 2009Periodontitis is a chronic infective disease of the gums caused by bacteria present in dental plaque. This condition induces the breakdown of the tooth supporting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontitis is a chronic infective disease of the gums caused by bacteria present in dental plaque. This condition induces the breakdown of the tooth supporting apparatus until teeth are lost. Surgery may be indicated to arrest disease progression and regenerate lost tissues. Several surgical techniques have been developed to regenerate periodontal tissues including guided tissue regeneration (GTR), bone grafting (BG) and the use of enamel matrix derivative (EMD). EMD is an extract of enamel matrix and contains amelogenins of various molecular weights. Amelogenins are involved in the formation of enamel and periodontal attachment formation during tooth development.
OBJECTIVES
To test whether EMD is effective, and to compare EMD versus GTR, and various BG procedures for the treatment of intrabony defects.
SEARCH METHODS
The Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE were searched. Several dental journals were hand searched. No language restrictions were applied. Authors of randomised controlled trials (RCTs) identified, personal contacts and the manufacturer were contacted to identify unpublished trials. The last electronic search was conducted on 4 February 2009.
SELECTION CRITERIA
RCTs on patients affected by periodontitis having intrabony defects of at least 3 mm treated with EMD compared with open flap debridement, GTR and various BG procedures with at least 1 year of follow-up. The outcome measures considered were: tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), bone levels from the bottom of the defects on intraoral radiographs, aesthetics and adverse events. The following time points were to be evaluated: 1, 5 and 10 years.
DATA COLLECTION AND ANALYSIS
Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by at least two authors. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). It was decided not to investigate heterogeneity, but a sensitivity analysis for the risk of bias of the trials was performed.
RESULTS
A total of 13 trials were included out of 35 potentially eligible trials. No included trial presented data after 5 years of follow-up, therefore all data refer to the 1-year time point. A meta-analysis including nine trials showed that EMD treated sites displayed statistically significant PAL improvements (mean difference 1.1 mm, 95% CI 0.61 to 1.55) and PPD reduction (0.9 mm, 95% CI 0.44 to 1.31) when compared to placebo or control treated sites, though a high degree of heterogeneity was found. Significantly more sites had < 2 mm PAL gain in the control group, with RR 0.53 (95% CI 0.34 to 0.82). Approximately nine patients needed to be treated (NNT) to have one patient gaining 2 mm or more PAL over the control group, based on a prevalence in the control group of 25%. No differences in tooth loss or aesthetic appearance as judged by the patients were observed. When evaluating only trials at a low risk of bias in a sensitivity analysis (four trials), the effect size for PAL was 0.62 mm (95% CI 0.28 to 0.96), which was less than 1.1 mm for the overall result. Comparing EMD with GTR (five trials), GTR showed significantly more post-operative complications (three trials, RR 0.12, 95% CI 0.02 to 0.85) and more REC (0.4 mm 95% CI 0.15 to 0.66). The only trial comparing EMD with a bioactive ceramic filler found statistically significantly more REC (-1.60 mm, 95% CI -2.74 to - 0.46) at the EMD treated sites.
CONCLUSIONS
One year after its application, EMD significantly improved PAL levels (1.1 mm) and reduced PPD (0.9 mm) when compared to a placebo or control, however, the high degree of heterogeneity observed among trials suggests that the results have to be interpreted with great caution. In addition, a sensitivity analysis indicated that the overall treatment effect might be overestimated. The actual clinical advantages of using EMD are unknown. With the exception of significantly more postoperative complications in the GTR group, there was no evidence of clinically important differences between GTR and EMD. Bone substitutes may be associated with less REC than EMD.
Topics: Aggressive Periodontitis; Alveolar Bone Loss; Bias; Bone Regeneration; Bone Transplantation; Chronic Periodontitis; Dental Enamel Proteins; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Randomized Controlled Trials as Topic; Regression Analysis; Tooth Loss; Treatment Outcome
PubMed: 20467602
DOI: No ID Found