Search Results (113)

Calcium silicate-based repair materials are widely used in endodontics, and bioinspired polymeric biomodification may influence their cellular response. However, the cytotoxicity profile of mineral trioxide aggregate (MTA) modified with Octenisept^® or with an acetic acid-based chitosan vehicle has not been specifically evaluated in a controlled design comparing chitosan-modified MTA groups under parallel MTA extract and direct solution exposure conditions, although biomodifier effects may differ when tested alone and when incorporated into an MTA matrix. This in vitro study evaluated the MTT-based cytotoxicity profile of MTA subjected to bioinspired chitosan-based biomodification in human periodontal ligament fibroblasts (hPDLFs), using Octenisept^® as an antiseptic comparator biomodifier and 1% acetic acid as the vehicle control. Extracts of unmodified-MTA, MTA + 1% acetic acid, MTA + 1% chitosan, MTA + 3% chitosan and MTA + Octenisept^® were tested at 100%, 50% and 25% concentrations. The corresponding solutions were tested under direct exposure at 100%, 50%, 25% and 12.5%. Cell viability was assessed after 24 and 72 h using the MTT assay, and values below 70% were considered cytotoxic according to ISO 10993-5. Direct solution exposure produced stronger cytotoxicity, particularly for Octenisept^®. Among the MTA extract groups, only MTA + 1% chitosan maintained non-cytotoxic cell viability at 72 h under undiluted extract conditions. Full article

Objectives: This scoping review summarized the evidence on the biocompatibility of pit and fissure sealants, focusing on cytotoxicity, genotoxicity, and overall biological safety of commercial and experimental materials evaluated in vitro and in vivo. Methods: Following the PRISMA-ScR guidelines, eligibility was defined using the Population, Concept, and Context (PCC) framework: the population comprised cell cultures, animal models, or human participants exposed to sealants; the concept was biocompatibility, including cytotoxicity, genotoxicity, and inflammatory or tissue response; and the context encompassed commercial and experimental pit and fissure sealants used in preventive dentistry, particularly in pediatric populations. PubMed and Scopus platforms were searched without restrictions on publication year or language. Studies assessing biocompatibility (cytotoxicity, genotoxicity, inflammatory or tissue response) in cell cultures, animal models, or humans were eligible; those evaluating only clinical efficacy were excluded. Two reviewers independently performed study selection and data extraction. Results: Of 406 records (291 after deduplication), 10 studies were included—nine in vitro and one in vivo. Resin-based sealants predominated, mainly assessing residual monomers (TEGDMA, Bis-GMA) and their effects on fibroblasts, keratinocytes, periodontal ligament cells, and buccal epithelial cells. TEGDMA was released most frequently, whereas Bis-GMA showed the highest cytotoxicity. Experimental sealants containing nano-calcium fluoride, calcium phosphate, bioactive glass, or antibacterial monomers generally showed favorable biocompatibility, although high additive concentrations reduced cell viability. The single in vivo study reported good biocompatibility without significant genotoxicity. Conclusions: Pit and fissure sealants generally show acceptable biocompatibility and remain safe for caries prevention, although the biological response depends on composition, degree of polymerization, and residual monomer release. Further standardized long-term in vivo research is needed, particularly in pediatric populations. Full article

Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as α3β1 and α6β4 support barrier integrity, whereas α5β1 may facilitate microbial interaction and inflammatory signaling. β2 integrins and α4β1 contribute to leukocyte recruitment and inflammatory amplification, whereas increased α9β1-associated signaling and reduced αvβ6-mediated regulation of transforming growth factor β (TGF-β) may promote inflammatory persistence. Matrix-associated integrins, including α2β1 and α11β1, support extracellular matrix (ECM) organization and mechanotransduction, whereas αvβ3 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired β1 integrin-dependent signaling and potentially reduced αvβ5-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades. Full article

Background/Objectives: Autophagy is a key degradative pathway involved in orthodontic tooth movement. DNA damage-regulated autophagy modulator 1 (DRAM1), a protein that plays a central role in the degradation of autophagic cargo, exhibits differential regulation in human periodontal ligament (hPDL) fibroblasts under compressive force. Single-nucleotide polymorphisms (SNPs) may influence force-induced gene expression. Therefore, this study investigated the impact of DRAM1 SNPs on its expression in hPDL fibroblasts under compression force. Methods: The hPDL sample comprised cells of 59 patients. A physiological compressive strain of 2 g/cm³ was used to simulate orthodontic tooth movement. Total RNA from hPDL fibroblasts was isolated to determine DRAM1 relative gene expression under loaded conditions and in a physiological control. Furthermore, a genotyping analysis of six SNPs within the DRAM1 gene (rs756534 (G/T), rs2138257 (C/T), rs2176092 (C/T), rs4622329 (A/G), rs10860812 (A/G), and rs4764657 (A/G)) was performed using real-time polymerase chain reaction. DRAM1 expression was com-pared among genotypes of each SNP using an alpha of 5%. Linear regression analysis was then employed to evaluate SNP-SNP interaction. Results: The relative DRAM1 gene expression was not statistically significantly different (p > 0.05) according to the geno-types. The SNP-SNP interaction did not demonstrate any statistically significant associ-ation either. Conclusions: DRAM1 gene expression in hPDL fibroblasts under orthodontic compression may not be regulated by the studied intronic SNPs in the gene encoding DRAM1. Full article

Background/Objectives: Peri-implant diseases, encompassing peri-implant mucositis and peri-implantitis, affect 43% and 18.8–23% of implant-bearing patients, respectively, representing significant clinical challenges in implant dentistry. While mechanical debridement remains foundational, biologically active materials offer promising adjunctive regenerative strategies. This narrative review synthesises current evidence regarding five biologically active materials: enamel matrix derivative (EMD), platelet-rich fibrin (PRF), fibroblast growth factor-2 (FGF-2), recombinant human platelet-derived growth factor-BB (rhPDGF-BB/GEM 21S^®), and polynucleotide–hyaluronic acid combinations (Regenfast^®). Methods: The relevant literature was identified using electronic databases, including MEDLINE, PubMed, Scopus, and Google Scholar. This review focused on clinical studies and randomised controlled trials with a minimum follow-up of six months investigating biologically active materials in peri-implant disease management. Material mechanisms, clinical efficacy, therapeutic limitations, and evidence quality were systematically evaluated. Attention was directed toward identifying genuine biological distinctions between peri-implant and periodontal disease contexts. Results: EMD demonstrates efficacy exclusively within multimodal surgical protocols, with isolated application yielding limited benefits. rhPDGF-BB shows superior periodontal regenerative capacity; however, dedicated peri-implantitis trials remain absent. FGF-2 exhibits paradoxical osteogenic suppression despite bone fill achievement, limiting peri-implant applicability. PRF and Regenfast^® demonstrate a mechanistically sound rationale yet lack substantive peri-implant disease validation. The critical findings revealed that peri-implant regeneration fundamentally differs from periodontal regeneration: implants lack periodontal ligament anatomy, rendering ligamentogenic differentiation-promoting agents biologically inappropriate. Conclusions: Contemporary biologically active materials demonstrate compelling periodontal efficacy yet remain inadequately validated for peri-implantitis management. This disparity reflects authentic biological distinctions rather than insufficient investigation. Until multicentre randomised controlled trials stratify efficacy across distinct peri-implant disease presentations, practitioners must prioritise evidence-based surgical fundamentals—meticulous decontamination, strategic grafting, and optimised wound healing—integrating biologically active materials judiciously within comprehensive, anatomy-respecting treatment protocols. Full article

Periodontal disease represents a major global health burden, beginning with gingivitis and progressing to periodontitis, which causes connective tissue breakdown, alveolar bone resorption, and eventual tooth loss. Beyond local pathology, periodontitis is a chronic inflammatory condition with systemic associations, including cardiovascular disease, diabetes, and metabolic disorders. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have emerged as promising candidates for periodontal regeneration. This review aimed to map the current evidence on MSC-derived EVs (MSC-EVs) in periodontal regeneration, focusing on their mechanisms of action, therapeutic potential, and translational challenges. A comprehensive literature search was conducted across a major biomedical database (PubMed) to identify preclinical and clinical studies investigating MSC-EVs in the context of periodontitis. Data were charted on EV cargo composition, biological functions, regenerative outcomes, and reported limitations. Evidence indicates that MSC-EVs encapsulate bioactive molecules—including antimicrobial peptides, proteins, lipids, and microRNAs—that modulate immune responses, suppress pro-inflammatory signaling, and promote angiogenesis and tissue repair. In periodontal models, MSC-EVs attenuate osteoclast activity, enhance fibroblast proliferation, and stimulate extracellular matrix remodeling, supporting regeneration of periodontal ligament and alveolar bone. Exosome-based approaches demonstrate advantages such as reduced immunogenicity, improved safety, and feasibility for storage and standardization. However, most findings remain preclinical, with limited human data available. To bridge the translational gap, well-designed clinical trials are needed to confirm efficacy and safety while addressing regulatory challenges, GMP standards, and outcome measures. Harnessing their regenerative capacity while mitigating side effects may guide precision-targeted therapies, and continued mechanistic studies with standardized production will be key to advancing MSC-EVs into clinical practice. Full article

Background/Objectives: Many products that claim to have anti-aging effects have been reported, but their relative potency is not clear. In this study, the in vitro replicative lifespan extension (RLE) activity of various groups of physiologically active substances was compared by using the updated “overlay method”. Methods: Human dermal and periodontal ligament fibroblasts (HDFa, HPLF) were inoculated into the inner 60 wells of 96-well microplate, surround by sterile water to prevent the water evaporation. At Day 1 and Day 8, the cells were overlayed with wide ranges of concentrations (0.01–100 µM) of samples without medium change. Viable cell number was measured by the MTT method at Day 15 and then corrected for the variation in cell growth due to the location of inoculated cells. The RLE value was calculated as the maximum cell proliferation rate relative to the control. Results: Cell density of HDFa and HPLFs at subculture decreased with the passage number, and their growth was stopped at 56 or 85 population doubling levels (PDLs), respectively. Hydrocortisone showed the highest RLE values among six hormones, followed by three plant extracts, sodium ascorbate and quercetin. On the other hand, other antioxidants, chlorogenic acid, phenylpropanoids, vanilloids, and bacterial products showed little or no RLE effects. However, for HPLF cells, hydrocortisone did not show RLE effects while oxytocin showed slight stimulation. Conclusions: When differences in proliferation due to cell seeding position were corrected, the biphasic dose response curve of most of the compounds significantly reduced. The present study suggests the significant role of hormones for the regulation of the long-term aging process. To confirm systemic or clinical anti-aging effects, further in vitro and in vivo experiments are needed. Full article

Zirconium is a widely used material in the field of dentistry, employed for implants and their components as well as for the creation of crowns and veneers. Given that its biocompatibility has been studied and demonstrated in various fields of application, it is necessary to analyze how surface modification of this material influences its properties. The purpose of this study was to analyze the biocompatibility, initial adhesion (48 h), and morphology of periodontal ligament stem cells (PDLSCs) seeded on different zirconium surfaces treated with laser micropatterning, as well as plastic coverslips as a control. The Neubauer chamber was used to count the cells adhered to each of the sets, and confocal and scanning electron microscopy were employed to examine the adhesion and morphology of periodontal ligament stem cells on each of the zirconium surfaces studied. Results: Statistically significant differences were found in terms of primary cell adhesion, with sets 3 (grid topography) and 4 (channel topography) showing the most favorable characteristics for fibroblast adhesion. It was concluded that regular and moderately rough surfaces promoted better cell proliferation and development. Full article

Periodontal disease is a chronic inflammatory condition that destroys tooth-supporting tissues, particularly the alveolar bone and the periodontal ligament, and effective regenerative therapies remain limited. While the role of metabolic–epigenomic crosstalk in determining cell fate is well established, the specific mechanism by which a tricarboxylic acid (TCA) cycle metabolite can modulate chromatin regulation to promote periodontal regeneration remains to be elucidated. The impact of one TCA cycle metabolite, alpha-ketoglutarate (α-KG), was examined in human periodontal ligament fibroblasts cultured under osteogenic induction and profiled by ALP assays, RT-qPCR, analyses of multiple histone modifications, ATAC-seq, and RNA-seq. α-KG increased ALP activity and upregulated genes associated with osteogenesis and the extracellular matrix (ECM). ATAC-seq revealed minimal genome-wide accessibility changes, whereas histone analyses showed reduced H3K27me3, consistent with an epigenetic mechanism that does not require extensive chromatin opening. The RNA-seq identified 14 upregulated α-KG-induced genes, including multiple components of the OGN-OMD-PLAP1/ASPN-ECM2 loci, supporting an osteogenic/ECM transcriptional program. In a mouse periodontal regeneration model, oral administration of α-KG enhanced alveolar bone regeneration and reduced H3K27me3 signals and collagen-rich tissue organization within the periodontal ligament space. These findings identify α-KG as a metabolite-driven epigenetic modulator that alleviates H3K27me3-mediated repression and supports periodontal regeneration. Full article

The biological compatibility of endodontic sealers is a key determinant of periapical tissue healing. This in vitro study investigated the cytotoxic, pro-inflammatory, and redox-related effects of eight endodontic sealers on human periodontal ligament fibroblasts (HPdLFs): Biopulp (Chema-Elektromet), AH Plus (Dentsply Sirona), MTA Fillapex (Angelus), EndoSeal MTA (Maruchi), GuttaFlow (Coltène), AH Plus Bioceramic (Dentsply Sirona), TotalFill BC (FKG Dentaire SA), and BioRoot TM (Septodont). Cells were exposed for 24 h to 10-fold-diluted sealer extracts prepared in accordance with the manufacturers’ instructions, while control samples underwent identical procedures without sealer contact. Oxidative stress biomarkers, antioxidant defense parameters, protein oxidation indices, apoptotic activity (caspase-3), pro-inflammatory cytokines (IL-1, IL-6), and cell viability (MTT assay) were assessed. Under the applied conditions, all materials induced only limited global oxidative stress, with most alterations reflecting selective protein and glycoxidative modifications. Nevertheless, AH Plus, MTA Fillapex, and the calcium hydroxide-based Biopulp exhibited a less favorable redox profile and greater protein oxidation compared with calcium silicate-based sealers. AH Plus and EndoSeal MTA were associated with increased IL-6 release, whereas EndoSeal MTA moderately elevated IL-1 levels. BioRoot TM demonstrated the lowest cytokine expression, and TotalFill BC preserved high cell viability. Caspase-3 activity remained comparable across all experimental groups, indicating minimal induction of apoptosis. Full article

Objectives: Combining mechanical plaque control, the physical removal of oral biofilm, with chemical plaque control, the use of agents to inhibit biofilm formation, is effective in preventing periodontal disease. Chlorogenic acid (CGA) found in coffee beans has medicinal effects, such as anti-inflammatory and antibacterial properties. Periodontal pathogens are difficult to reach in certain areas with traditional self-care tools, such as toothbrushes. Additionally, the viscous biofilm is difficult to remove using mechanical plaque control alone. Therefore, this study aimed to evaluate the efficacy of CGA in chemical plaque control. Methods: The mRNA and protein expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPDLs) in the presence of CGA were analyzed using reverse transcription-qPCR and enzyme-linked immunosorbent assay. Additionally, the proliferation levels of oral bacteria in the presence of CGA were evaluated. Results: CGA suppressed mRNA and protein expression levels of the inflammatory cytokines, interleukin (IL)-1β and IL-8, in HGFs and HPDLs stimulated with Porphyromonas gingivalis LPS. Furthermore, CGA inhibited bacterial proliferation of Streptococcus mutans, Aggregatibacter actinomycetemcomitans, P. gingivalis, and Fusobacterium nucleatum. Conclusions: This study demonstrated that CGA exhibits anti-inflammatory effects on gingiva and periodontal ligaments, and antibacterial effects against oral bacteria. These results indicate the potential application of CGA in chemical plaque control and suggest its use in preventing periodontal disease progression. Full article

Background: Periodontitis is a disease characterized by the destruction of periodontal tissue and tooth loss. The molecular mechanisms behind this disease, however, are not clearly understood. Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death that seems to play a role in periodontal pathogenesis by increasing oxidative stress and reducing tissue regeneration. Objective: The current narrative review aims to summarize current knowledge of the involvement of ferroptosis in periodontal tissue destruction and potentially to identify new targets of therapy. Methods: A comprehensive search of PubMed, Embase, and Web of Science databases was conducted. Original human, animal, and in vitro studies published in English were selected. Data on experimental models, molecular markers, and key outcomes were extracted and synthesized in the review. Results: After screening, four studies were identified and selected. Ferroptosis activation in periodontal ligament fibroblasts, stem cells, and gingival tissues was associated with increased ACSL4 and decreased GPX4 expression, iron accumulation, and oxidative stress. The administration of Ferrostatin-1 or antioxidants like curcumin seemed to reduce inflammation and alveolar bone loss in vivo. Transcriptomic analyses further revealed immune-related ferroptosis gene signatures in human periodontitis tissues. Conclusions: Ferroptosis represents a crucial mechanism in periodontal tissue destruction through not yet completely understood. Understanding these molecular pathways could be the key to developing new therapeutic strategies for periodontal treatment. Full article

Vitamin D₃ is a fat-soluble steroid essential for bone metabolism, immune modulation, and inflammation control, all critical for periodontal health. Its active form, 1,25-dihydroxyvitamin D₃, binds to the vitamin D receptor (VDR) in periodontal cells, including periodontal ligament stromal cells, fibroblasts, osteoblasts, and macrophages, enhancing osteogenesis, antimicrobial defenses, and anti-inflammatory responses. Clinical and experimental evidence demonstrates that adequate systemic vitamin D₃ levels and local activation in gingival tissues improve outcomes of nonsurgical and surgical periodontal therapies, reducing probing pocket depth (PPD), clinical attachment loss (CAL), and gingival inflammation. Dose-dependent supplementation shows greater clinical efficacy, and emerging evidence supports potential topical applications. This review integrates molecular mechanisms with clinical findings, highlighting the therapeutic potential of vitamin D₃ in periodontal disease management. Full article

Background/Objectives: Peri-implantitis is a chronic inflammatory condition affecting tissues surrounding dental implants and is characterized by progressive marginal bone loss that can ultimately lead to implant failure. Reduced vascularization and impaired immune clearance in peri-implant tissues contribute to persistent inflammation and limited therapeutic efficacy. MicroRNAs (miRNAs), particularly miR-21, have emerged as key regulators of inflammatory responses and bone remodeling. The objective of this study was to develop a bioactive dental implant coating capable of locally delivering miR-21 to modulate inflammation and promote peri-implant tissue regeneration, thereby preventing peri-implantitis. Methods: Cationic nanoparticles were synthesized using lecithin and low-molecular-weight polyethylenimine (PEI) as a non-viral delivery system for miR-21. Lecithin was employed to enhance biocompatibility, while PEI functionalization provided a positive surface charge to improve miRNA complexation and cellular uptake. The resulting lecithin–PEI nanoparticles (LEC–PEI NPs) were incorporated into a chitosan-based coating and applied to titanium implant surfaces to obtain a sustained miR-21–releasing system (miR21-implant). Transfection efficiency and biological activity were evaluated in human periodontal ligament fibroblasts (hPDLFs) and compared with a commercial transfection reagent (Lipofectamine). Release kinetics and long-term activity of miR-21 from the coating were also assessed. Results: MiR-21-loaded LEC–PEI nanoparticles demonstrated significantly higher transfection efficiency than Lipofectamine and retained marked biological activity in hPDLFs relevant to peri-implantitis prevention. The chitosan-based nanoparticle coating enabled controlled and sustained miR-21 release over time, supporting prolonged modulation of inflammatory and osteogenic signaling pathways involved in peri-implant tissue homeostasis. Conclusions: The miR21-implant system, based on lecithin–PEI nanoparticles incorporated into a chitosan coating, represents a promising therapeutic strategy for peri-implantitis prevention. By enabling sustained local delivery of miR-21, this approach has the potential to preserve peri-implant bone architecture, modulate chronic inflammation, and enhance the osseointegration of titanium dental implants. Full article

Matrix metallopeptidases (MMPs) are enzymes that, in balance with their inhibitors, play a vital role in extracellular matrix remodelling, particularly during orthodontic tooth movement (OTM). Despite growing interest, significant research is still required to fully comprehend the mechanisms and signalling pathways involved in periodontal ligament remodelling and OTM, particularly those mediated by MMPs. This review explores recent in vitro and in vivo evidence on how specific MMPs—namely, MMP-1, -2, -3, -8, -9, -12, -13, and -14—respond to compressive and tensile forces, regulate collagen degradation, and influence periodontal ligament fibroblast and osteoblast behaviour, ultimately shaping tissue resorption and formation. We also summarize the roles of periodontal ligament cells, hypoxia, the neurovascular and immune systems, and well-known molecules—including receptor activator of nuclear factor kappa β, receptor activator of nuclear factor kappa β ligand, osteoprotegerin, macrophage colony-stimulating factor, tumour necrosis factor α, transforming growth factor, and interleukins—in orchestrating these responses. Finally, we address the clinical relevance of these pathways, highlighting the potential for therapeutic strategies targeting MMPs activity. Overall, this review underscores the pivotal contribution of MMPs to extracellular matrix turnover and tissue adaptation during OTM and suggests that modulating the MMPs/tissue inhibitors of matrix metallopeptidase (TIMPs) balance may enhance orthodontic outcomes. Full article