Search Results (352)

Orthodontic tooth movement (OTM), a complex biological process driven by orchestrated bone remodeling, involves osteoclastic bone resorption and osteoblastic bone formation in response to mechanical force. Traditionally, OTM-related cell death has been discussed in terms of apoptosis and necrosis. However, recent advances in cell death research have revealed various forms of regulated cell death (RCD) beyond these conventional categories. This review summarizes the current understanding of the diverse RCD pathways and their roles in various cell populations during OTM. It delineates the involvement of distinct RCD mechanisms, including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis. On the compression side, these RCD pathways in periodontal ligament (PDL) cells, cementoblasts, cementocytes, and bone-related cells actively drive inflammatory responses, promote bone resorption, and contribute to root resorption. Conversely, on the tension side, specific RCD pathways, notably autophagy in the PDL and osteocytes, play crucial roles in promoting osteogenesis and tissue repair. Collectively, cell death is not merely a passive elimination of cells but actively functions as a critical switch for alveolar bone remodeling during OTM. Understanding these multifaceted RCD mechanisms provides novel insights into the biological regulation of tooth movement and identifies potential therapeutic targets for enhancing tooth movement efficiency and mitigating adverse effects. Full article

Mechanical loading is a central cue in periodontal tissues, where compression of the periodontal ligament guides remodeling and orthodontic tooth movement (OTM). However, most mechanobiology studies have used two-dimensional cultures with poorly defined loading, and the role of autophagy under realistic three-dimensional compression remains unclear. In this study, we constructed a three-dimensional static compression model by encapsulating human periodontal ligament cells in collagen–alginate–CaSO₄ hydrogels, whose swelling, degradation, and viscoelasticity approximate those of native matrix. When exposed to a controlled static compressive stress, the cells exhibited an early autophagic response with increased ATG7, Beclin1, and LC3-II/LC3-I; accumulation of LC3-positive puncta; and reduced p62 expression between 4 and 8 h. Pharmacological modulation showed that activation of AKT-mTOR signaling suppressed this response, whereas its inhibition further augmented autophagy, identifying AKT-mTOR as a negative regulator of compression-induced autophagy. Together, these findings demonstrate that moderate static compression drives AKT-mTOR-dependent autophagy in periodontal ligament cells and establish a simple hydrogel platform for quantitative studies of periodontal remodeling. 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

Objectives: The purpose of this study is to compare the differences between lemon-derived exosome-like nanovesicles (LELNs) stored at −80 °C, −20 °C, and 4 °C for one month and freshly isolated LELNs, in terms of characterization and anti-inflammatory effects on periodontal ligament cells, aiming to identify suitable storage conditions for LELNs. Methods: Nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and micro bicinchoninic acid assay (BCA) were conducted to access the characterization differences. LPS-induced human periodontal ligament cells were used as an in vitro inflammatory model, and the changes in biological functions were examined by qRT-PCR and ELISA. Results: LELNs stored at −80 °C retained the highest particle and protein concentration and showed the least aggregation and heterogeneity in size on TEM images, while the average particle sizes shown by NTA were similar. And LELNs exhibited similar anti-inflammatory effects on periodontal ligament cells after one month of storage at −80 °C, −20 °C, and 4 °C. Conclusions: We found that LELNs can maintain in vitro anti-inflammatory ability when stored at either −80 °C, −20 °C, or 4 °C for one month, while storing at −80 °C maintains the concentration and uniform particle size best. Full article

Magnetite (Fe₃O₄) nanoparticles are biocompatible, non-toxic, and easily functionalized. Coating them with mesoporous silica (mSiO₂) offers high surface area, pore volume, and tunable surface chemistry for drug loading. In this study, Fe₃O₄ magnetic nanoparticles were synthesized and coated with mSiO₂ shells enriched with calcium ions (Ca²⁺), aiming to enhance bioactivity for bone regeneration and tissue engineering. Different synthesis routes were tested to optimize shell formation Their characterization confirmed the presence of a crystalline Fe₃O₄ core with partial conversion to maghemite (Fe₂O₃) post-coating. The silica shell was mostly amorphous and the optimized samples exhibited mesoporous structure (type IVb). Calcium incorporation slightly altered the magnetic properties without significantly affecting core crystallinity or particle size (11.68–13.56 nm). VSM analysis displayed symmetric hysteresis loops and decreased saturation magnetization after coating and Ca²⁺ addition. TEM showed spherical morphology with some agglomeration. MTT assays confirmed overall non-toxicity, except for mild cytotoxicity at high concentrations in the Ca²⁺-enriched sample synthesized by a modified Stöber method. Their capacity to induce human periodontal ligament cell osteogenic differentiation, further supports the potential of Fe₃O₄/mSiO₂/Ca²⁺ core–shell nanoparticles as promising candidates for bone-related biomedical applications due to their favorable magnetic, structural, and biological properties. Full article

Objectives: Periodontitis is a multifactorial inflammatory disease initiated by pathogenic bacteria, such as Porphyromonas gingivalis. Resolvin D1 (RvD1) plays a pivotal role in inflammation resolution. This study aimed to identify the mechanism of the regulatory effects of RvD1 on the inflammatory response of human periodontal ligament cells (hPDLCs). Methods: To investigate the mechanism of RvD1’s impact on the hPDLCs, RNA-sequencing (RNA-seq) was used and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to assess the signaling pathways in which NF-κB and MAPK were determined to play a significant role. Alterations in NF-κB and MAPK pathways were verified by immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), and Western blotting (WB). The expression of RvD1 and lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) was assessed by IF and WB. Inflammatory cytokine interleukin (IL) 6 and IL-1β release was measured by ELISA. Results: GO and KEGG analyses indicated that RvD1 regulates the inflammatory process in PDLCs primarily via TLR4-MyD88-mediated NF-κB and MAPK signaling. RvD1 suppressed lipopolysaccharide (LPS)-induced TLR4 and MyD88 expression, inhibited phosphorylation of NF-κB p65 and its inhibitor IKBKB, and attenuated phosphorylation of p38 MAPK, ERK, and JNK. ALX/FPR2 was expressed on hPDLCs and was further upregulated upon treatment with RvD1. RvD1 significantly down-regulated the IL-6 and IL-1β levels in LPS-stimulated hPDLCs. Conclusions: RvD1 regulates the inflammatory response of LPS-stimulated hPDLCs by the TLR4-MyD88-MAPK and TLR4-MyD88-NF-κB signaling pathways, suggesting the potential role of RvD1 in restoring periodontal tissue homeostasis by regulating PDLC response to inflammatory and infectious stimuli. Full article

Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., “long-COVID,” “post-acute sequelae of SARS-CoV-2 infection,” “PASC,” “post-COVID-19,” “long-haul COVID”) and oral/periodontal diseases (e.g., “periodontal disease,” “periodontitis,” “gingiva,” “oral disease,” “dental”), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein–Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships. Full article

Background and Objectives: The use of proanthocyanidins (PACNs) alongside standard periodontal treatment procedures can improve periodontal and peri-implant tissue healing. The present study aimed to evaluate the effect of different concentrations of Pelargonium sidoides root extract (PSRE) on periodontal tissue proliferation in comparison with chlorhexidine digluconate (CHX). Materials and Methods: A cell culture study was performed using human gingival fibroblast (HGF-1) and human periodontal ligament fibroblast (HPDLF) lines. The HGF-1 cell line was exposed to CHX (the gold standard treatment in periodontal diseases) and PSRE at concentrations of up to 800 μg/mL, which were compared with negative controls. HGF-1 viability and proliferation were evaluated using fluorescence tests and the PrestoBlue assay, respectively. In addition, the cell proliferation induction ability of PSRE was evaluated by treating HGF-1 and HPDLF cells with PSRE at 25 and 50 μg/mL concentrations and measuring the TGFβ-1 levels using TGFβ-1 ELISA. Results: When comparing the effects of the 25 μg/mL PSRE treatment to the control, a statistically significant difference in HGF-1 cell growth was observed (0.297 ± 0.048 (mean ± SE) and 0.203 ± 0.01, respectively; p = 0.006). The strongest cytotoxic effect on HGF-1 cells was observed with CHX (0.007 ± 0.006, p < 0.001 vs. control). The HGF-1 and HPDLF cells showed statistically significant increases in TGFβ-1 levels when treated with PSRE at 25 and 50 μg/mL compared with the control (352.38 ± 31.32 (mean ± SE) and 330.99 ± 26.53 versus 161.07 ± 15.11 in HGF-1 cells; 397.53 ± 18.1 and 399.91 ± 27.61 versus 137.7 ± 16.54 in HPDLF cells, p < 0.001). Additionally, no negative effects were detected at low PSRE concentrations (less than 100 μg/mL). Conclusions: The results of this study suggested that PACNs may promote HGF-1 and HPDLF cell proliferation. In contrast, CHX showed cytotoxic effects. Full article

Polylactic acid (PLA) and its composites with hydroxyapatite (HA) have been studied in the field of bone repair applications. The objective of this study was to evaluate the biocompatibility of PLA/HA at different concentrations and to analyze early adhesion of periodontal ligament stem cells (PDLSCs). Cells were seeded in two 24-well plates, each containing six disk-shaped samples of PLA/HA (10%, 15% and 20%) and six control samples and then examined using scanning electron microscopy. Twelve 96-well plates were prepared with different elution concentrations (1/1, 1/2, 1/4, and 1/8) to assess biocompatibility using MTT cell viability and Hoechst 33342 assays at 24, 48, and 72 h. PLA/HA 20% showed the highest early adhesion (p = 0.0057), with cells adopting a more elongated morphology. The MTT assay revealed no differences in viability between concentrations (p = 0.6196), whereas the Hoechst assay demonstrated the highest viability for PLA/HA 20% (p < 0.0001). Overall, PLA promoted cell adhesion, with the 20% formulation providing the greatest adhesion. All concentrations maintained high viability, and longer culture time enhanced both adhesion and viability. Full article

Periodontitis is a prevalent chronic inflammatory disease that leads to the progressive destruction of periodontal tissues and remains the primary cause of tooth loss worldwide. Despite advances in regenerative approaches—including stem cell therapy, scaffold-based tissue engineering, and guided tissue regeneration—the complete and functional restoration of the periodontal ligament remains a major clinical challenge. Stem-cell-based therapies and advanced biomaterials have emerged as promising strategies in regenerative medicine, offering potential for restoring periodontal structure and function. Among cells, periodontal-ligament-derived stem cells (PDLSCs) show exceptional regenerative potential due to their ability to differentiate into cementoblasts, osteoblasts, and other cell types essential for periodontal repair. In recent years, a variety of biomaterials with distinct specifications and properties have been utilized to repair periodontal damage. In addition to the inherent properties of biomaterials, the morphology and structural characteristics of these materials as bioequivalents for periodontal regeneration are also critical considerations. Furthermore, recent studies emphasize that mechanical stimulation plays a considerable role in directing stem cell differentiation, gene expression, matrix organization, and modulating inflammatory responses in periodontal regeneration. Canonical parameter ranges for systematic analysis indicate that cyclic stretch strain of 1–20% at 0.1–0.5 Hz (6–30 cycles/min) typically increases the expression of osteogenic markers (RUNX2, ALP, OCN) and matrix components (Col1) in PDLSCs. Conversely, higher values (>15%) often bias the response toward inflammatory pathways (IL-6, PGE2). Static compression above 2 g/cm² consistently stimulates the secretion of pro-inflammatory cytokines (IL-6, IL-8) and alters the RANKL/OPG balance in favor of osteoclastogenesis. Significant heterogeneity in response across studies will be analyzed by examining key methodological variables, including specific loading regimens (duration, frequency patterns) and culture conditions (e.g., serum/osteogenic supplements), which critically modulate mechanotransduction outcomes. This review summarizes current progress in periodontal regenerative medicine, emphasizing cellular and biomaterial considerations, as well as biofabrication techniques, with a particular focus on the influence of mechanical forces on PDLSCs. We discuss cellular responses to mechanical stimuli, including changes in gene expression, cytoskeletal organization, proliferation, and differentiation. Combining biological knowledge with advances in bioprinting and the study of mechanobiology, we finally discuss promising opportunities for improving periodontal regeneration that can be applied in the future in clinical practice. Full article

Hydrogels are versatile biomaterials for controlled drug delivery and tissue regeneration due to their biocompatibility and tunable degradation. Hydrogel was synthesized with a gelatin type A/polyvinyl alcohol functionalized with aqueous extract of roasted green tea (10% w/v) and evaluated its physiobiological performance in vitro. Degradation was assessed under enzymatic (collagenase II, trypsin) and hydrolytic conditions; swelling was performed with distilled water, cytocompatibility was tested on human periodontal ligament stem cells by MTT; antibacterial activity was measured against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The hydrogel showed complete hydrolytic degradation within 60 min and enzymatic degradation within 70 min, the hydrogel increased its mass by approximately 6.3 times relative weight, reached its maximum swelling in the range of 478–537%, (19% for the experimental group), while maintaining PDLSC viability (>80%). It exhibited significant antibacterial activity (inhibition: S. aureus 78.6%, S. mutans 67.4%, E. coli 73.2%). Importantly, in osteogenic medium, the hydrogel enhanced osteogenic differentiation of PDLSCs, evidenced by increased calcium deposition and positive Alizarin Red staining versus controls. These data position the gelatin/PVA/roasted green tea hydrogel as a bioactive, resorbable candidate for dental applications—particularly as an antimicrobial dressing and adjunct for periodontal bone regeneration material. Full article

Periodontal regeneration remains one of the most demanding challenges in oral bioengineering due to the structural complexity of the periodontium and the inflammatory microenvironment accompanying disease. Conventional surgical and pharmacological therapies often fail to achieve full restoration of bone, ligament and cementum, prompting the development of cell-based and biomaterial-assisted approaches. This review summarizes current advances in cellular technologies for periodontal regeneration, emphasizing the biological rationale, material design and delivery methods shaping next-generation treatments. We discuss stem-cell-based strategies employing periodontal ligament, dental pulp and mesenchymal stem cells, their paracrine and immunomodulatory roles, and how their therapeutic potential is enhanced through integration into engineered scaffolds. Recent progress in hydrogel systems, microspheres, decellularized matrices and 3D bioprinting is analyzed, highlighting how structural cues, bioactive nanoparticles and gene-modified cells enable multi-tissue regeneration. Emerging delivery and biofabrication techniques, from manual seeding to automated and in situ printing, are reviewed as key determinants of clinical translation. The convergence of bioprinting precision, immune-responsive biomaterials and personalized cellular constructs positions periodontal bioengineering as a rapidly maturing field with strong prospects for functional restoration of diseased oral tissues. Full article

Periodontal ligament stem cells (PDLSCs) represent a promising cell source for true periodontal regeneration due to their ability to form bone, cementum, and functional ligament. This review critically synthesised twelve in vivo studies (rats = 5, pigs = 2, dogs = 2, sheep = 2, one human trial) evaluating PDLSC transplantation for periodontal defects. A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library (to May 2025) identified 358 records, of which 12 met predefined inclusion criteria. Data extraction encompassed cell source, scaffold, dose, follow-up, and quantitative regenerative outcomes. Nine studies reported cell doses (5 × 10⁵–2 × 10⁷ cells) and six PDLSC regeneration rates (33–100%). After normalisation for host mass, effective delivery ranged from 10⁵ to 10⁶ cells·kg⁻¹, with optimal outcomes typically above 10⁵ cells·kg⁻¹. PDLSC transplantation consistently enhanced alveolar bone, cementum, and periodontal-ligament regeneration compared with scaffold-alone or untreated controls, with the highest outcomes obtained using biocompatible scaffolds such as Hydroxyapatite/Tricalcium Phosphate (HA/TCP), Gelfoam, or amniotic membrane. Both autologous and allogeneic PDLSC achieved equivalent performance and excellent safety, while xenogeneic models confirmed immune tolerance. Despite encouraging results, the evidence remains preliminary—most studies were short-term and small-scale, and only one randomised human trial has been published. Standardisation of cell preparation, scaffold selection, dosing (absolute and mass-normalised), and follow-up is urgently needed. Future research should include Good Manufacturing Practice (GMP)-compliant clinical trials and mechanistic studies on PDLSC differentiation, paracrine signalling, and exosome-mediated effects to consolidate their translational potential for predictable periodontal regeneration. Full article

Background/Objectives: The optimal healing process following root canal treatment involves biological apical sealing through new cementum formation. Bone morphogenetic protein 7 (BMP-7) has recently gained attention as a potential regulator of cementoblast differentiation and periodontal regeneration. However, its effects on periodontal ligament fibroblasts (PDLFs) and the underlying mechanisms remain incompletely understood. This study aimed to investigate whether BMP-7 induces cementoblast-like differentiation of PDLFs both in vivo and in vitro via the BMP-SMAD signaling pathway. Methods: In a rat pulpectomy model, root canals were treated with or without BMP-7 and examined histologically and immunohistochemically for F-spondin (Spon1) expression. In vitro, human PDLFs were stimulated with BMP-7, and analyses of mineralization, cementoblast marker expression, alkaline phosphatase activity, and SMAD-1/5/9 phosphorylation were conducted. Results: Immunohistochemical analysis revealed that Spon1-positive regions increased around the apical area following BMP-7 treatment, suggesting the induction of cementoblast-like differentiation. In vitro, BMP-7 enhanced the expression of cementoblast-associated genes and mineral deposition while activating SMAD-1/5/9 signaling. Phosphorylation was suppressed by the BMP receptor inhibitor LDN-193189, indicating canonical BMP-SMAD pathway involvement. Conclusions: Although the specific concentration range of maximal activity remains to be determined, the findings collectively suggest that BMP-7 can promote cementoblast-like differentiation of PDLFs and may contribute to apical healing through cementum-related mechanisms. These results provide mechanistic and biological insights that support the potential of BMP-7 as a modulator for biologically favorable periapical tissue regeneration following root canal therapy. Full article

Periodontitis is a chronic inflammatory condition of the periodontal tissues, ultimately leading to their destruction. The periodontal ligament is a key structure that not only secures the teeth within the alveolus but can also act as a source of numerous mediators involved in the development of inflammation in periodontal tissues. The aim of this study was to investigate the effect of leptin on periodontal ligament cells and their secretion of selected pro-inflammatory mediators that may contribute to the pathogenesis of periodontal disease. The study was conducted on cultured periodontal ligament cells stimulated with leptin. The effect of leptin was assessed on the expression of selected cytokines implicated in the pathogenesis of periodontal disease (IL-1, IL-6, IL-8, IL-10, IL-17, IL-18, and tumour necrosis factor-alpha [TNF-α]) at the mRNA level, as well as on the protein concentrations of these cytokines in culture supernatants. Assessments were carried out after 12, 24, and 48 h of leptin stimulation. The results showed a statistically significant effect of leptin on IL-6 and IL-8 expression at both the mRNA and protein levels. For IL-1, a transient increase in mRNA expression and protein concentration was observed, persisting up to 24 h. A decrease in IL-10 mRNA expression was noted after 48 h of leptin stimulation, with no corresponding effect on IL-10 protein concentration. No significant effect of leptin was found on IL-17 or IL-18 protein concentrations in periodontal ligament cell cultures. These findings suggest that leptin may contribute to the pathogenesis of periodontitis by modulating the expression of certain pro-inflammatory cytokines in periodontal ligament cells. Full article