Search Results (190)

Material selection is crucial to hard tissue regeneration, and matching scaffold properties to those of the target tissue can improve clinical outcomes. This study compared the physicochemical, mechanical, and biological performance of fibrous scaffolds fabricated from polycaprolactone (PCL), polydioxanone (PDO), and gelatin methacryloyl (GelMA) for hard tissue regeneration. Polymeric fibers were produced by electrospinning, and their morphological, physical, and mechanical properties were characterized by scanning electron microscopy (SEM, n = 2), swelling and degradation analyses (n = 8), water contact angle measurements (n = 16), and tensile testing (n = 8). In addition, periodontal ligament stem cells (PDLSCs), alveolar bone marrow stem cells (aBMSCs), and dental pulp stem cells (DPSCs) were seeded onto the scaffolds to evaluate cell spreading (n = 4), viability (n = 8), and mineralized matrix formation (n = 6). Data were analyzed using one- or two-way ANOVA followed by appropriate post hoc tests (α = 5%). All polymers formed homogeneous fibrous scaffolds, with diameters within the nanoscale range. PDO and GelMA showed higher swelling than PCL, while PCL retained approximately 95% of its initial mass after three months. PCL and PDO showed higher elongation at break, tensile strength, and Young’s modulus than GelMA. Both PDO and GelMA displayed contact angles below 90°, with GelMA showing the lowest values. In vitro, all polymers were cytocompatible: PDO and GelMA enhanced DPSC viability at 7 days, whereas GelMA produced the highest viability for PDLSCs and aBMSCs at that time point. GelMA also promoted the highest mineralized matrix formation for DPSCs and PDLSCs, with no significant differences among polymers for aBMSCs. Overall, GelMA scaffolds promoted greater cell viability and mineralized matrix formation, while PCL and PDO provided superior mechanical properties, highlighting the importance of balancing biological and mechanical requirements when designing scaffolds for hard tissue regeneration. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus and obesity, have recently attracted attention for their potential effects on periodontal tissues. This systematic review aimed to evaluate the current evidence regarding the relationship between GLP-1-based therapies and periodontal health, with particular emphasis on anti-inflammatory, osteogenic, and regenerative mechanisms. A comprehensive literature search of PubMed, Web of Science, and Embase databases identified 22 eligible studies, including in vitro, animal, and human investigations. The available evidence suggests that GLP-1RAs such as liraglutide and exendin-4 may attenuate periodontal inflammation, reduce alveolar bone loss, and enhance osteogenic differentiation of periodontal ligament and dental pulp stem cells through modulation of pathways including MAPK/ERK, Wnt/β-catenin, NF-κB, and PKCβ2. Clinical observations additionally indicate a bidirectional relationship between periodontitis and incretin signalling, with periodontal therapy associated with increased systemic GLP-1 levels. However, the current evidence remains heterogeneous and is largely limited to preclinical and observational studies. Randomised clinical trials are required to determine the clinical efficacy and therapeutic relevance of GLP-1-based therapies in periodontitis management. Full article

Background: Tooth root caries and periodontal tissue loss remain major challenges in elderly and periodontally compromised patients, while current restorative materials lack combined antibacterial and regenerative properties. Objective: The objective of this study was to develop a novel metformin-containing antibacterial composite for root cavity restorations to prevent recurrent caries and potentially promote periodontal tissue regeneration. Methods: Experimental composites contained 5% dimethylaminohexadecyl methacrylate (DMAHDM), varying metformin concentrations (2.5–15%), and glass fillers. Mechanical and antibacterial properties as well as cytocompatibility toward human periodontal ligament stem cells (hPDLSCs) were investigated. Results: The experimental composites achieved flexural strengths of 67.9 to 50.1 MPa (n = 6), significantly higher than (41.3 ± 3.4 MPa) of commercial control Vitremer (p < 0.05), while maintaining clinically acceptable elastic moduli of 3.7–3.1 GPa. Experimental composites achieved an 8-log reduction in Streptococcus mutans (S. mutans) biofilms and significantly reduced lactic acid production and metabolic activity compared to biofilms on commercial controls. The composite containing 15% metformin demonstrated acceptable cytocompatibility toward hPDLSCs under clinically relevant diluted conditions, matching commercial controls (p > 0.1). Conclusions: These findings suggest that this novel composite possesses potent antibacterial activity, acceptable cytocompatibility, and adequate mechanical properties, making it promising for multifunctional root caries restorations. Full article

Background/Objectives: Endodontic perforation repair requires biomaterials that balance sealing ability with minimal cellular injury. AH Plus (epoxy resin-based) remains widely used despite cytotoxicity concerns. CeraSeal (calcium silicate-based bioceramic) is a potentially more biocompatible alternative. However, comparative data on sealer-induced cytotoxicity and inflammatory responses remain limited. This study compared the cytotoxicity and inflammatory profiles of CeraSeal and AH Plus using in vitro and in vivo approaches. Methods: Human periodontal ligament stem cells (hPDLSCs) were exposed to sealer extracts (1:4 AH Plus, 1:8 CeraSeal) for 120 h. Cell death was assessed by MTT, Live/Dead, LDH release, and Annexin V/PI flow cytometry. Oxidative stress was quantified via ROS generation (DCFH-DA). In a rat furcation perforation model (n = 8 teeth/group), inflammatory markers (TNF-α, IL-1β, CD68), osteogenic activity (ALP), and osteoclasts (TRAP) were evaluated. Results: AH Plus was associated with significantly greater necrotic cell death (357.6 ± 47.6% LDH release vs. CeraSeal 128.8 ± 37.5%; p = 0.0079) and reduced hPDLSC viability at all time points (p < 0.0001). ROS generation was comparable between sealers (~32–35%, p > 0.05). In vivo, IL-1β was higher in AH Plus-treated tissues (52.25 vs. 24.88 cells/mm²; p = 0.0002), while TNF-α and CD68 were greater in CeraSeal (p ≤ 0.0011). ALP was higher in AH Plus (median 6.15 vs. 3.68; p = 0.0002), with no difference in TRAP-positive osteoclasts. Morphometric analysis showed superior cellular preservation with CeraSeal (p = 0.0079), while inflammatory infiltration was higher in CeraSeal (p = 0.0002). Conclusions: AH Plus was associated with a necrotic-inflammatory profile with elevated IL-1β and higher ALP expression. CeraSeal demonstrated better cellular preservation, lower LDH release, and a distinct inflammatory signature (higher TNF-α and CD68). These findings establish comparative response profiles for the two sealers and support CeraSeal as a potentially biocompatible alternative, though further mechanistic studies are warranted. Full article

Periodontal disease remains one of the leading causes of tooth loss worldwide, highlighting the need for effective regeneration of alveolar bone, periodontal ligament, and cementum. The structural complexity and unique biological behavior of these tissues have historically posed significant challenges for clinical regeneration strategies. The primary therapeutic approach used is guided bone regeneration; however, it has certain limitations, such as morbidity, low structural integrity and dimensional stability. Recent advances in 3-dimensional (3D) bioprinting have made it possible to fabricate customized scaffolds with precise architecture and spatial organization that closely mimic normal periodontal structures. The incorporation of multifunctional nanocomposite biomaterials and nanoparticles further enhances the performance of the scaffolds by increasing mechanical strength, bioactivity and controlling degradation rates. These advanced scaffolds function as dynamic microenvironments that support cell adhesion, proliferation and differentiation, ultimately promoting tissue regeneration. Furthermore, their multifunctional properties allow for the controlled release of growth factors, anti-inflammatory and antimicrobial agents, as well as the incorporation of stem cells and bioactive molecules that facilitate angiogenesis. This review investigates and critically evaluates modern approaches for the regeneration of periodontal tissues through scaffolds, biomaterials and 3D bioprinting technologies, as well as to assess their effectiveness compared to established clinical practices. Full article

GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes and obesity and are increasingly relevant in periodontal and implant practice. This review covers mechanisms, preclinical and early human evidence, and practical periodontal considerations; the structured database search is conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) and the International Committee of Medical Journal Editors (ICMJE) principles. Two pathways explain GLP-1RAs’ relevance: indirect effects from better glycemic control, weight loss, and reduced inflammation; and direct tissue effects involving GLP-1R signaling and the GLP-1/dipeptidyl peptidase-4 (DPP-4) axis. Preclinical studies show reduced inflammation, osteoclast activity, and alveolar bone loss, along with improved periodontal stem cell function under hyperglycemia or inflammation via Nuclear Factor-kappaB (NF-kappaB), Wingless-related integration site (Wnt)/beta-catenin, and Mitogen-Activated Protein Kinase (MAPK) pathways. Animal studies on implants and local delivery, including exendin-4 platforms, suggest osteometabolic benefits. Human data are limited and mostly observational, and confounders include metabolic status, smoking, medication, and nutrition. Oral side effects such as xerostomia and dehydration are also noted. At present, GLP-1RA therapy should be regarded as a contextual modifier of periodontal risk and healing capacity rather than as a stand-alone periodontal therapy. Full article

Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety. Full article

Periodontal ligament mesenchymal stem cells (PL-MSCs) are vital for both periodontal regeneration and alveolar bone maintenance, including their turnover during orthodontic therapy. Chronic periodontal inflammation, mainly caused by Gram-negative bacterial lipopolysaccharides (LPS), interferes with osteogenic differentiation and leads to bone loss. Increasing evidence indicates that long non-coding RNAs (lncRNAs) link inflammatory signaling to osteogenic regulation, but their specific role in LPS-driven modulation of PL-MSC osteogenesis is not well understood. The aim of this study was to assess the effects of LPS from two bacterial strains on PL-MSCs differentiation. Human PL-MSCs were cultured under standard stem cell or osteogenic conditions and treated with LPS from Escherichia coli or Porphyromonas gingivalis. Mineralization was assessed using Alizarin Red staining. Osteogenic differentiation was evaluated through immunocytochemical analysis of osteopontin, collagen type 1, osteocalcin, osteonectin, and dentin matrix protein-1 (DMP-1). Expression levels of lncRNAs growth arrest-specific transcript 5 (GAS5), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), maternally expressed gene 3 (MEG3) and Nuclear Enriched Abundant Transcript 1 (NEAT1) were measured by real-time PCR at 6, 24 and 48 h of LPS exposure. Exposure to E. coli LPS significantly inhibited extracellular matrix mineralization and decreased the expression of key osteogenic markers, indicating impaired osteoblast maturation. In contrast, P. gingivalis LPS caused a partial, dysregulated osteogenic response, marked by increased expression of osteopontin, osteonectin, and dentin matrix protein-1 (DMP-1), but without complete differentiation. LPS types altered lncRNA expression profiles, suggesting that non-coding regulatory networks are involved in inflammation-induced osteogenic dysregulation. Multivariate analyses showed decreased expression of GAS5, MEG3, and MALAT1 in the LPS vs. CTR comparison, decreased COL1A1 in LPS-PG vs. CTR, and increased OSTEOPONTIN in LPS vs. CTR. Differentiation was significantly associated with reduced expression of XIST and NEAT1. Time exerted significant effects on GAS5, MEG3, XIST, and MALAT1, with lower expression at 48 h compared with 6 h, and on COL1A1, which was significantly reduced at both 24 h and 48 h relative to 6 h. Bacterial LPS disrupt osteogenic differentiation of PL-MSCs depending on the species, affecting matrix formation, mineralization, and lncRNA expression. These findings highlight lncRNA-mediated communication between inflammatory signals and osteogenic pathways, providing new insights into the molecular mechanisms of inflammation-related bone remodeling in periodontal disease and orthodontic movements. Targeting lncRNA-regulated pathways could be a promising strategy to enhance periodontal regeneration during inflammation and also ensure optimum outcomes in orthodontic therapy. Full article

Orthodontic tooth movement (OTM) is driven by force-induced alveolar bone remodeling, yet the molecular mechanisms by which periodontal ligament stem cells (PDLSCs) sense and transduce mechanical signals remain incompletely understood. Here, we identify the epigenetic regulator HELLS as a compressive force-responsive gene and investigate its role as a mechanosensitive mediator in human PDLSCs (hPDLSCs). Compressive force downregulated HELLS expression both in vitro and in a mouse OTM model. Functionally, siRNA-mediated HELLS knockdown impaired osteogenic differentiation, as evidenced by reduced Alizarin Red S staining and alkaline phosphatase activity, and induced global transcriptomic changes indicative of altered mechanotransduction pathways. Moreover, HELLS knockdown increased YAP and RANKL expression and potentiated osteoclast differentiation of co-cultured RAW264.7 cells. Finally, we identified E2F1 as a candidate transcription factor mediating the force-induced downregulation of HELLS. Collectively, these findings establish HELLS as a potential mechano-epigenetic regulator in hPDLSCs, and suggest that its force-induced downregulation may contribute to alveolar bone remodeling during OTM by simultaneously attenuating osteogenesis and enhancing pro-osteoclastogenic signaling via transcriptional reprogramming. 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

Objectives: pH-responsive zeolite imidazolate framework-8 (ZIF-8) enables selective release of 5-fluorouracil (5-FU) within the acidic tumor microenvironment. However, the direct effects of ZIF-8 itself on cancer cells or surrounding tissues remain unclear. Since oral cancer involves interactions between epithelial tumor cells and stromal cells, comparing the effects of ZIF-8 on epithelial cancer cells and orofacial mesenchymal stem/stromal cells (OMSCs) is critical to understanding its broader biological impact. Methods: The effects of ZIF-8 on SCC7 epithelial cancer cells and OMSCs, including periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs), were evaluated using RNA sequencing, nuclear staining, live/dead assays, and immunocytochemistry. Cells were treated with 0, 1, 10, or 100 μg/mL ZIF-8. Based on nuclear staining results, live/dead viability assays were conducted on SCC7 and DPSCs treated with 0 or 100 μg/mL ZIF-8. Apoptosis-related markers (Bax, caspase-3, caspase-6, and caspase-10) were assessed following exposure to 100 μg/mL ZIF-8. Results: Transcriptomic analysis revealed that ZIF-8 not only facilitates selective 5-FU release but also directly induces apoptosis in SCC7 cells compared with 5-FU alone. At 100 μg/mL ZIF-8, SCC7 viability was significantly reduced, whereas OMSC viability was preserved. Nonviable SCC7 cells increased markedly compared with controls, while DPSCs showed no significant change. Apoptosis-related signaling was also elevated in SCC7 cells compared with DPSCs. Conclusions: ZIF-8 at 100 μg/mL selectively inhibits SCC7 growth while sparing OMSC viability and apoptosis. 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

Background: Despite extensive preclinical evidence that statins enhance osteogenesis and the widespread clinical use of platelet-rich fibrin (PRF), the clinical effectiveness of statin-incorporated PRF (SIM-PRF) in limiting peri-implant crestal bone loss remains insufficiently validated. Objectives: To address the mentioned gap, we integrated in vitro assays on human periodontal ligament stem cells (hPDLSCs) with a controlled clinical trial to test whether SIM-PRF reduces early and 12-month marginal bone loss versus PRF alone and PRF with bone graft. Methods: In vitro, cytotoxicity, migration and osteogenic differentiation were assessed, in addition to the effect on basal inflammatory markers. Clinically, 24 immediate-implant cases were randomized to receive PRF, PRF+SIM, or PRF+bone graft, with CBCT-based crestal bone change measured at 0–3, 3–6, and 6–12 months. Results: Flow cytometry confirmed the mesenchymal identity of the isolated hPDLSCs, which exhibited dose-dependent responses to SIM treatment. Lower SIM concentrations (0.1 μM) enhanced osteogenic differentiation, as evidenced by increased mineralization, alkaline phosphatase activity, and expression of osteogenic markers (RUNX2 and osteocalcin), while maintaining cell viability and migration. Both SIM concentrations (0.1 μM and 1 μM) significantly reduced basal pro-inflammatory cytokine expression (TNF-α and IL-6). Radiographic analysis revealed significantly reduced crestal bone loss (p < 0.001) in the PRF-SIM and PRF-Bone groups compared to PRF alone, particularly during early postoperative intervals (0–3 and 3–6 months). Notably, no significant difference was observed between the PRF-SIM and PRF-Bone groups (p > 0.05) in preserving the peri-implant bone. Conclusions: These findings highlight the potential of SIM-loaded PRF as an effective, biocompatible, and patient-friendly approach to enhance bone regeneration and implant success. Full article

Phosphatase and Tensin Homolog (PTEN) functions in numerous biological processes, encompassing cell proliferation, growth, self-renewal, and differentiation. This study examined the modulatory function of the PTEN inhibitor in periodontal ligament stem cells (PDLSCs). PDLSCs were treated with VO-OHpic at a concentration range from 0.625 to 5 μM. MTT assay and Coomassie Blue staining were conducted to determine cell viability and colony-forming unit ability, respectively. The scratch assay was employed to examine cell migration. Mineral deposition and intracellular lipid accumulation were assessed. The qRT-PCR and immunofluorescence were used to evaluate mRNA and protein expression, respectively. RNA sequencing was employed for transcriptomic analysis. VO-OHpic exposure showed no cytotoxic effects in PDLSCs; however, at 5 μM, it markedly decreased colony-forming efficiency and impaired cell migration. Under osteogenic induction conditions, 5 μM VO-OHpic markedly attenuated mineralisation and downregulated the osteogenic marker gene expression partly through ERK signalling. Indeed, VO-OHpic impaired intracellular lipid accumulation during adipogenic differentiation, as evidenced by reduced expression of adipogenic marker genes. RNA sequencing analysis revealed that VO-OHpic treatment upregulated genes in the TGF-β and calcium signalling pathways, suggesting a regulatory role in PDLSC differentiation. In conclusion, PTEN regulates PDLSC colony formation, migration, and differentiation, suggesting a pivotal role for PTEN in maintaining periodontal tissue homeostasis. 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