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Annals of Periodontology Dec 2003Regeneration of tooth-supporting structures destroyed by periodontitis is a major goal of periodontal therapy. Periodontal tissue engineering utilizing growth and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Regeneration of tooth-supporting structures destroyed by periodontitis is a major goal of periodontal therapy. Periodontal tissue engineering utilizing growth and amelogenin-like factors (GAFs) applies advances in materials science and biology to regenerate alveolar bone, periodontal ligament, and cementum. Amelogenin-like factors (e.g., enamel matrix derivative [EMD]) and growth factors (e.g., platelet-derived growth factor [PDGF] and bone morphogenetic proteins [BMPs, also considered morphogens]) have demonstrated pleotrophic effects on the stimulation of several key events required for tissue regeneration including DNA synthesis, chemotaxis, differentiation, and matrix synthesis.
RATIONALE
GAFs have been used for the treatment of periodontal disease as shown in preclinical and clinical studies. This systematic review evaluates the evidence to support the utilization of EMD and growth factors (GFs) for periodontal repair and regeneration associated with natural teeth.
FOCUSED QUESTION
In patients with periodontal osseous defects, what is the effect of GAFs compared with controls on clinical, radiographic, histologic, adverse, and patient-centered outcomes?
SEARCH PROTOCOL
Two investigators searched MEDLINE, pre-MEDLINE, and the Cochrane Oral Health Group trials register for clinical and preclinical studies published in English. Hand searches were performed on the International Journal of Periodontics and Restorative Dentistry, Journal of Clinical Periodontology, Journal of Dental Research, Journal of Periodontology, and Journal of Periodontal Research. Searches were performed for articles published through April 2002. In addition, investigators contacted manufacturers of GAF products for related unpublished data and studies in progress.
INCLUSION CRITERIA
Randomized controlled clinical trials (RCTs), cohort studies, case-control studies, case reports, and preclinical (animal) randomized controlled investigations that included a cohort population diagnosed with periodontal disease and presenting data on intrabony/interproximal defects and/or furcation defects were screened.
EXCLUSION CRITERIA
In vitro studies or those that did not include quantifiable data with respect to clinical or bone measures were not included.
DATA COLLECTION AND ANALYSIS
Meta-analyses were performed for studies that fulfilled the eligibility criteria for the following continuous variables: clinical attachment level (CAL), probing depth (PD), or bone level (radiographic, re-entry, or histologic). Heterogeneity was assessed to determine whether the differences among therapies were due to systematic confounding factors (as noted in study quality assessments).
MAIN RESULTS
1. Eight studies, representing 7 RCTs and 1 quasi-experimental study, representing a total population of 511 subjects were analyzed with respect to EMD. 2. The majority of the remaining papers had a low evidence rating. 3. Most reports were case studies or case series without controls. 4. There were insufficient data to conduct a meta-analysis on the effect of growth factors used in periodontal repair around teeth.
REVIEWERS' CONCLUSIONS
1. There is evidence supporting the use of EMD for periodontal osseous defects to improve CAL and reduce PD, although long-term benefits have not been established. 2. EMD has demonstrated notable consistency among the studies investigated in terms of superiority to controls (in general compared to open flap debridement [OFD]). 3. EMD appears to be safe for single and multiple administrations in terms of lack of elicitation of antibody responses or other local/systemic inflammatory events. 4. Preclinical and initial clinical data for growth factors appear promising but are insufficient to draw definitive conclusions at this time.
Topics: Alveolar Bone Loss; Amelogenin; Animals; Bone Morphogenetic Proteins; Consensus; Dental Enamel Proteins; Fibroblast Growth Factor 2; Furcation Defects; Growth Substances; Humans; Periodontium; Platelet-Derived Growth Factor; Wound Healing
PubMed: 14971254
DOI: 10.1902/annals.2003.8.1.193 -
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 -
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 -
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 -
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 -
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