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Journal of Tissue Engineering and... Dec 2021The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in... (Meta-Analysis)
Meta-Analysis
The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human-derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta-analysis of pre-clinical studies. The systematic review and network meta-analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre-clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm ), bone volume density (g/cm ) and bone height (mm) data was extracted. The analysis was carried out using network meta-analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP-2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF-5/TCP ranked best in the bone area (mm2), rhPDGF-BB/Equine ranked best in bone height (mm), rhBMP-2 ranked best in the percentage of new bone fill, rhBMP-2/ACS ranked best in new cementum formation, and rhGDF-5/b- TCP/PLGA ranked best in connective tissue attachment and junctional epithelium. There were no adverse effects identified in the literature that could affect the different outcomes for regeneration in intrabony defects. Various recombinant factors are effective in promoting the regeneration of both soft and hard tissue supporting structures of the periodontium. However, when considering different outcomes, different agents, associated or not with biomaterials, ranked best. Keeping into account the limited transferability of results from animal studies to the clinical setting, the choice of the most appropriate formulation of bioactive agents may depend on clinical needs and purpose.
Topics: Animals; Becaplermin; Bone Morphogenetic Protein 2; Bone Regeneration; Horses; Humans; Periodontium; Recombinant Proteins; Transforming Growth Factor beta
PubMed: 34585856
DOI: 10.1002/term.3250 -
Journal of Applied Biomaterials &... 2023Polycaprolactone (PCL) is a highly recognized synthetic polymer for its biocompatibility, ease of fabrication and mechanical strength in bone tissue engineering. Its...
BACKGROUND
Polycaprolactone (PCL) is a highly recognized synthetic polymer for its biocompatibility, ease of fabrication and mechanical strength in bone tissue engineering. Its applications have extended broadly, including regeneration of oral and maxillofacial lost tissues. Its usefulness has brought attention of researchers to regenerate periodontal lost tissues, including alveolar bone, periodontal ligament and cementum. The aim of this systematic review was to obtain an updated analysis of the contribution of PCL-based scaffolds in the alveolar bone regeneration process.
METHODS
This review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews. A computerized search of the PubMed, EBSCO, Scielo and Web of Science databases was performed, restricting literature search to published studies in English or Spanish between January 2002 and March 2023. Database search returned 248 studies which were screened based on title, author names and publication dates.
RESULTS
Data from 17 studies were reviewed and tabulated. All studies combined PCL with other biomaterials (such as Alginate, hydroxyapatite, bioactive glass, poly (lactic-co-glycolic acid)), growth factors (BMP-2, rhCEMP1), and/or mesenchymal stromal cells (adipose-derived, bone marrow, periodontal ligament or gingiva mesenchymal stromal cells). PCL scaffolds showed higher cell viability and osteoinductive potential when combined with bioactive agents. Complementary, its degradation rates were affected by the addition or exposure to specific substances, such as: Dopamine, Cerium Oxide, PLGA and hydrogen peroxide.
CONCLUSIONS
PCL is an effective biomaterial for alveolar bone regeneration in periodontally affected teeth. It could be part of a new generation of biomaterials with improved regenerative potential.
Topics: Biocompatible Materials; Bone Regeneration; Guided Tissue Regeneration; Tissue Engineering; Tissue Scaffolds
PubMed: 37978859
DOI: 10.1177/22808000231211416 -
Biomolecules Apr 2022Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs... (Review)
Review
Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs are associated with insulin resistance and poor glycemic control. Recently, inflamed periodontal tissues and certain oral bacteria were observed to increase the local and systemic AGE levels in both normoglycemic and hyperglycemic individuals. Although hyperglycemia induced AGE and its effect on the periodontal tissues is known, periodontitis as an endogenous source of AGE formation is not well explored. Hence, this systematic review is aimed to explore, for the first time, whether inflamed periodontal tissues and periodontal pathogens have the capacity to modulate AGE levels in individuals with or without T2DM and how this affects the glycemic load. Six electronic databases were searched using the following keywords: (Periodontitis OR Periodontal disease OR Periodontal Inflammation) AND (Diabetes mellitus OR Hyperglycemia OR Insulin resistance) AND Advanced glycation end products. The results yielded 1140 articles, of which 13 articles were included for the review. The results showed that the mean AGE levels in gingival crevicular fluid was higher in individuals with diabetes mellitus and periodontitis (521.9 pg/mL) compared to healthy individuals with periodontitis (234.84 pg/mL). The serum AGE levels in normoglycemic subjects having periodontitis was higher compared to those without periodontitis (15.91 ng/mL vs. 6.60 ng/mL). Tannerella forsythia, a common gram-negative anaerobe periodontal pathogen in the oral biofilm, was observed to produce methylglyoxal (precursor of AGE) in the gingival tissues. Increased AGE deposition and activate of AGE receptors was noted in the presence of periodontitis in both normoglycemic and hyperglycemic individuals. Hence, it can be concluded that periodontitis can modulate the local and systemic levels of AGE levels even in absence of hyperglycemia. This explains the bidirectional relationship between periodontitis and development of prediabetes, incident diabetes, poor glycemic control, and insulin resistance.
Topics: Diabetes Mellitus; Humans; Hyperglycemia; Insulin Resistance; Periodontitis; Periodontium
PubMed: 35625570
DOI: 10.3390/biom12050642 -
Frontiers in Bioengineering and... 2021Orthodontic tooth movement is based on the remodeling of tooth-surrounding tissues in response to mechanical stimuli. During this process, human periodontal ligament...
Orthodontic tooth movement is based on the remodeling of tooth-surrounding tissues in response to mechanical stimuli. During this process, human periodontal ligament cells (hPDLCs) play a central role in mechanosensing and mechanotransduction. Various models have been introduced to investigate the effect of tension on hPDLCs. They provide a valuable body of knowledge on how tension influences relevant genes, proteins, and metabolites. However, no systematic review summarizing these findings has been conducted so far. Aim of this systematic review was to identify all related studies reporting tension application on hPDLCs and summarize their findings regarding force parameters, including magnitude, frequency and duration. Expression data of genes, proteins, and metabolites was extracted and summarized. Studies' risk of bias was assessed using tailored risk of bias tools. Signaling pathways were identified by protein-protein interaction (PPI) networks using STRING and GeneAnalytics. According to our results, Flexcell Strain Unit and other silicone-plate or elastic membrane-based apparatuses were mainly adopted. Frequencies of 0.1 and 0.5 Hz were predominantly applied for dynamic equibiaxial and uniaxial tension, respectively. Magnitudes of 10 and 12% were mostly employed for dynamic tension and 2.5% for static tension. The 10 most commonly investigated genes, proteins and metabolites identified, were mainly involved in osteogenesis, osteoclastogenesis or inflammation. Gene-set enrichment analysis and PPI networks gave deeper insight into the involved signaling pathways. This review represents a brief summary of the massive body of knowledge in this field, and will also provide suggestions for future researches on this topic.
PubMed: 34513810
DOI: 10.3389/fbioe.2021.695053 -
Healthcare (Basel, Switzerland) May 2021(1) Background: Menopause is a physiological condition typified by drastic hormonal changes, and the effects of this transition have long-term significant clinical... (Review)
Review
(1) Background: Menopause is a physiological condition typified by drastic hormonal changes, and the effects of this transition have long-term significant clinical implications on the general health, including symptoms or physical changes. In menopausal women, the periodontium can be affected directly or through neural mechanism by oestrogen (E2) deficiency. The majority of the biological effects of E2 are modulated via both oestrogen receptor-α (ERα) and oestrogen receptor- β (ERβ). There is evidence that hypoestrogenism has a substantial impact on the aetiology, manifestation and severity of periodontitis, via the regulation of the expression of osteoprogesterin and RANKL in human periodontal ligament cells through ERβ. However, the mechanistic understanding of oestrogen in periodontal status has been partially clarified. The aim of this paper was to synopsize the recent scientific evidence concerning the link between the menopause and periodontitis, through the investigation of physio-pathological impact of the oestrogen deficiency on osteogenic differentiation of PDLSCs and PDLSC, as well as the dynamic change of ERα and ERβ. (2) Methods: Search was conducted for significant studies by exploring electronic PubMed and EMBASE databases, and it was independently performed by two researchers. All studies on the impact of oestrogen level on alveolar bone resorption were searched from 2005 to July 2020. Data selection was in concordance with PRISMA guidelines. (3) Results: Eight studies met the criteria and were included in this systematic review. All studies reported that oestrogen deficiency impairs the osteogenic and osteoblastic differentiation of PDL cells and oestrogen affects the bone formation capacity of cells. Seven studies were conducted on animal samples, divided into two groups: the OVX animals and animals who received the sham operation. (4) Conclusions: There is a multitude of data available showing the influence of menopause on periodontal status. However, the evidence of this line to investigation needs more research and could help explain the physiological linkage between menopause state and periodontal disease.
PubMed: 34066107
DOI: 10.3390/healthcare9050572 -
BMC Oral Health Jun 2021Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical...
BACKGROUND
Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical and systemic application of tetracyclines on pulpal and periodontal healing after tooth replantation.
METHODS
A comprehensive electronic search was conducted in six databases. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
After exclusion of 246 irrelevant papers, 14 animal studies and one human study were included in this review. The human study showed that avulsed permanent teeth treated with doxycycline did not show a better clinical outcome for pulp and periodontal healing compared with treatment with normal saline. As for animal studies, significant more pulpal healing was observed in immature teeth treated with topical doxycycline in two researches, while another one study showed that there is no difference between teeth treated with normal saline and teeth treated with doxycycline. Systemic doxycycline exerted no significant effect on pulpal revascularization illustrated by one research. Only one out of four articles illustrated the positive effect of systemic tetracyclines on periodontal healing. One paper reported that intracanal application of demeclocycline promoted favorable periodontal healing. Two articles showed topical doxycycline contributed to favorable periodontal healing, while five studies showed no significant effect of topical tetracyclines on periodontal healing.
CONCLUSIONS
As a result of data heterogeneity and limitations of the studies, the effect of topical or systemic application of tetracyclines on pulpal and periodontal healing is inconclusive. More studies are required to get more clinically significant conclusions.
Topics: Animals; Dental Pulp; Humans; Periodontal Ligament; Tetracyclines; Tooth Avulsion; Tooth Replantation; Wound Healing
PubMed: 34090399
DOI: 10.1186/s12903-021-01615-y -
Dentistry Journal May 2024the purpose of this systematic review was to assess the clinical and radiographic effect of subgingival-administered statins as an adjunct periodontal treatment in... (Review)
Review
BACKGROUND
the purpose of this systematic review was to assess the clinical and radiographic effect of subgingival-administered statins as an adjunct periodontal treatment in patients with periodontitis.
METHODS
Electronic literature searches in Medline/PubMed and the Cochrane Library were conducted to identify all relevant articles. Eligibility was based on inclusion criteria which included Randomized Controlled Trials (RCTs) published after 2010, where the periodontal variables were assessed before and after periodontal treatment in combination with a statin administration. The risk of bias was assessed with the ROBINS-2 tool. The outcome variables were probing depth, clinical attachment level, bleeding on probing, and bone fill in systematically healthy patients, patients with type 2 diabetes, and smokers.
RESULTS
Out of 119 potentially eligible articles, 18 randomized controlled trials were included with a total of 1171 participants. The data retrieved from the meta-analysis showed the positive effect that statins have as an adjunctive periodontal disease treatment. When comparing the different types of statins, the PD reduction in the Simvastatin group was significantly higher than the Atorvastatin group at 6 months and at 9 months, while no differences between statins were found for the rest of the outcomes. Over 66% of the articles presented an overall risk of bias with some concerns, making this a limitation of this present RCT.
CONCLUSIONS
The adjunct administration of statins has proven to have a positive effect on the periodontium by improving both clinical and radiographic parameters by a considerable margin.
PubMed: 38920851
DOI: 10.3390/dj12060150 -
Clinical Oral Investigations Mar 2022The aim of this study was to systematically update the evidence for associations between host genetic variants and subgingival microbial detection and counts.
OBJECTIVE
The aim of this study was to systematically update the evidence for associations between host genetic variants and subgingival microbial detection and counts.
MATERIALS AND METHODS
Following a previous systematic review (Nibali et al. J Clin Periodontol 43(11): 889-900, 15), an update of a systematic search of the literature was conducted in Ovid Medline, Embase, LILACS, and Cochrane Library for studies reporting data on host genetic variants and detection of microbes subgingivally published in the last 6 years.
RESULTS
A total of 19 studies were included in the review, from an initial search of 2797 titles. Studies consisted mainly of candidate gene studies and of one genome-wide analysis. A total of 62 studies were considered for summary findings, including 43 identified in the previous systematic review of studies published up to 2015. Meta-analyses were done when appropriate including both papers in the original review and in the update. Meta-analyses revealed lack of associations between IL1 composite genotype and subgingival detection of Aggregatibacter acinomycetemcomitans, Poprhyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Prevotella intermedia. Promising evidence is emerging from other genetic variants and from sub-analyses of data from genome-association studies. Among other studies with candidate-gene, target SNPs were mainly within the IL10, IL6, IL4, IL8, IL17A, and VDR gene.
CONCLUSIONS
IL1 composite genotype does not seem to be associated with subgingival microbial detection. Promising associations should be pursued by future studies, including studies employing -OMICS technologies.
CLINICAL RELEVANCE
A better knowledge of which host genetic variant predispose to subgingival microbial colonization and to the development of progression of periodontal disease could potentially help to better understand periodontal disease pathogenesis and help with its management.
Topics: Genotype; Gingiva; Gram-Negative Bacteria; Host Microbial Interactions; Humans; Interleukin-1
PubMed: 35122548
DOI: 10.1007/s00784-021-04233-8 -
Tissue Engineering and Regenerative... Jun 2022Platelet rich fibrin (PRF) has shown great potential in osteogenesis; however, some studies still question utilizing it as a grafting material. Thus, the aim of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Platelet rich fibrin (PRF) has shown great potential in osteogenesis; however, some studies still question utilizing it as a grafting material. Thus, the aim of this review is to evaluate the effect of PRF when used in socket and ridge preservation procedures.
METHODS
Electronic searches through MEDLINE, EMBASE, and Cochrane, Science Citation Index Expanded databases and manual searches of unpublished data, academic theses, and journals were conducted up until July 2021. The outcomes were to assess the ability of PRF as a graft material to preserve bone width, height, and density after tooth extraction.
RESULTS
Twelve studies were included in the review, using PRF showed significant results in all three outcomes when compared to no grafting at all, however when compared to other commonly used grafting materials it showed a lesser effect. On the other hand, most studies included reported mixing PRF with a graft material showed the best result. The meta-analysis also revealed the significant results in using PRF on the three outcomes.
CONCLUSION
The meta-analysis of the studies included proved the beneficial effect of PRF in socket preservation surgeries alone or in combination with other graft materials, but further individual multi-centre randomized controlled studies with appropriate sample size are still needed to further confirm our findings.
Topics: Osteogenesis; Platelet-Rich Fibrin; Tooth Extraction; Tooth Socket
PubMed: 35334092
DOI: 10.1007/s13770-021-00428-y -
Periodontology 2000 Feb 2023The aim of this study was to compare patient-reported outcome measures (PROMs) of soft tissue substitutes versus autogenous grafts for soft tissue augmentation... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to compare patient-reported outcome measures (PROMs) of soft tissue substitutes versus autogenous grafts for soft tissue augmentation procedures at implant sites. Comprehensive and systematic literature searches were performed until December 2021. A focused question was formulated based on the Population, Intervention, Comparison and Outcome criteria (PICO): In patients with dental implants undergoing soft tissue augmentation (P), do soft tissue substitutes (I) compared to autogenous soft tissue graft (SCTG [subepithelial connective tissue graft]) (C) limit the post-operative morbidity and other patient reported-outcomes measures (O). Randomized controlled clinical trials, prospective-, retrospective- and case-series studies were included. Meta-analyses were performed whenever possible and the results were expressed as weighted mean differences (WMD). A total of 29 clinical studies were included. For mucosal thickness gain, soft tissue substitutes significantly reduced the pain perception compared to SCTG (n = 4; WMD = 14.91 Visual Analog Scale [VAS] units; 95% confidence interval [CI] 6.42-23.40; P < .0006) based on a 0-100 VAS scale. Based on a 0-10 VAS scale, a borderline significance of pain reduction was found when soft tissue substitutes were applied (n = 4; WMD = 1.62 VAS units; 95% CI 0.01-3.23; P = .05). For keratinized tissue gain, soft tissue substitutes significantly reduced the pain perception after keratinized tissue augmentation compared to SCTG based on a 0-100 VAS scale (n = 2; WMD = 21.43 VAS units; 95% CI 12.58-30.28; P < .0001). Based on the 0-10 VAS scale, soft tissue substitutes significantly reduced the pain as compared to SCTG (n = 4; WMD = 1.65 VAS units; 95% CI 0.66-2.64; P = .001). Regarding pain medication, soft tissue substitutes required less painkillers (n = 6; WMD = 1.56 tablets; 95% CI 1.22-1.91; P < .00001) after soft tissue augmentation. The surgery time was significantly reduced when soft tissue substitutes were used (n = 5; WMD = 10.9 minutes; 95% CI 4.60-17.19; P < .00001). There were no significant differences in satisfaction, aesthetics, and quality of life (OHIP-14) between soft tissue substitutes and autogenous grafts following soft tissue augmentation at implants sites. Soft tissue substitutes, compared to autogenous grafts, significantly improve PROMs following soft tissue augmentation at implant sites. Soft tissue substitutes can reduce pain perception, amounts of painkillers and surgery time while achieving similar levels of patient´s satisfaction as autogenous grafts without impairing the clinical outcomes. The current evidence indicates that they constitute a valid and reliable alternative to minimize the invasiveness in soft tissue augmentation procedures at implant sites.
Topics: Humans; Dental Implants; Gingiva; Collagen; Connective Tissue; Prospective Studies; Quality of Life; Retrospective Studies; Pain
PubMed: 35950734
DOI: 10.1111/prd.12465