Periodontal Regeneration Research Articles

Optimizing collagen-based biomaterials for periodontal regeneration: clinical opportunities and challenges

Optimizing collagen-based biomaterials for periodontal regeneration: clinical opportunities and challenges

H2S-Scavenging Hydrogel Alleviating Mitochondria Damage to Control Periodontitis.

H2S, as a typical metabolite of periodontal pathogens, exhibits a clear positive correlation with the occurrence and development of periodontitis. H2S at physiological concentrations can regulate many biological processes. However, excess H2S in the periodontal pocket can trigger secretion of proinflammatory cytokines, cause oxidative stress, and result in mitochondrial damage and cell death in human gingival fibroblasts, exacerbating periodontitis development and periodontal tissue destruction. Worse, H2S facilitates bacteria survival and proliferation by maintaining bacterial redox balance and enhancing antibiotic resistance. Unfortunately, scavenging H2S during periodontitis treatment is usually ignored. Herein, a kind of hyaluronic acid methacryloyl/ZnO (HMZ) composite hydrogel with an H2S-scavenging ability was prepared to enhance periodontitis treatment. The HMZ hydrogel possessed good injectability and cytocompatibility and was able to remove H2S by a reaction with ZnO. As a result, the HMZ hydrogel was able to increase cell viability from 13% to 120% for human gingival fibroblasts and 22% to 94% for human periodontal ligament fibroblasts at 48 h, restore mitochondrial homeostasis, and alleviate cGAS-STING signaling pathway-mediated inflammation. Meanwhile, the HMZ hydrogel showed satisfactory antibacterial properties and efficiency of plaque biofilm removal. The in vivo results further confirmed that HMZ hydrogel decreased the concentration of H2S within the periodontal pocket from 0.7 to 0.8 mM to the normal level (0.3 to 0.4 mM), killed the bacteria in the periodontal tissues, inhibited osteoclast activity, relieved excess inflammation, and decreased the vertical distance between the cementoenamel junction and the alveolar bone crest from 1,175 µm to 798 µm on the 7th day and from 1,075 µm to 693 µm on the 14th day, achieving efficient periodontal bone regeneration. In brief, an H2S scavenging-based promising strategy was developed to enhance the therapeutic efficiency of periodontitis.

Thermosensitive Hydrogels for Periodontal Regeneration: A Systematic Review of the Evidence.

Thermosensitive hydrogels are now among the most commonly used biomaterials in tissue engineering. Due to their unique characteristics, this review aimed to evaluate the suitability of thermosensitive hydrogels in periodontal regeneration. PubMed, Scopus, and Web of Science databases were searched until March 25, 2024, to retrieve relevant articles. The eligibility criteria for the included studies were determined by the designed PICO elements. Results from each included study were extracted, focusing on the three main areas: thermosensitivity, cellular characteristics, and in vivo characteristics. Nineteen studies were included in our study. The thermosensitivity assessment of the hydrogels indicated a range of sol-gel transition times from 40 s to 20 min based on the type of polymers and the fabrication process. The cellular characterization was assessed based on three main cellular behaviors: cellular viability/proliferation, differentiation, and migration. The in vivo characterization was performed based on two main approaches: radiographic and histologic evaluation. The results indicated that the addition of bioactive agents could enhance the in vivo efficacy of thermosensitive hydrogels in periodontal regeneration through three main areas: antimicrobial, anti-inflammatory, and regenerative effects.

Dental Resin for Periodontal and Tooth Root Regeneration via Metformin to Enhance Osteogenic and Cementogenic Differentiation of Human Periodontal Ligament Stem Cells

ObjectivesThis study developed a novel dental resin incorporating metformin to repair root caries and periodontitis defects. The objectives were to: (1) Develop a novel dental resin with metformin release to fulfill the clinical requirements for mechanical properties; and (2) investigate the metformin release pattern and the effects on osteogenic and cementogenic differentiation of human periodontal ligament stem cells (hPDLSCs). MethodsResin specimens with different concentrations of metformin were fabricated. Metformin release was measured using high-performance liquid chromatography. Cellular growth and proliferation on resin were assessed. Alizarin red S staining and an alkaline phosphatase (ALP) activity were determined. Quantitative real-time reverse transcription PCR was employed to determine osteogenic and cementogenic differentiation. ResultsThe resin with 7.5% metformin had mechanical properties comparable to those of a commercial control, thus satisfying the clinical requirements (mean ± SD; n = 10). hPDLSCs showed robust growth and proliferation on resin. At 14 days, the number of hPDLSCs increased by four-fold (p > 0.1). ALP activity in the metformin group was 1.8 times higher than that of control (p < 0.05). At 21 days, the metformin group showed a significant increase in mineral synthesis. Metformin group had cementogenic and osteogenic differentiation values that were 2.5 and 2.3 times higher, respectively, than control without metformin (p < 0.05). SignificanceA metformin-resin was formulated that greatly promoted both cementogenic and osteogenic differentiation for the first time. This resin was mechanically strong and supported hPDLSC adhesion, growth and proliferation. This resin substantially enhanced hPDLSC osteogenic and cementogenic differentiation, yielding mineral synthesis of hPDLSCs more than 2-fold that of control without metformin. This new metformin-resin shows promise for the restoration of tooth root caries and the regeneration of periodontal tissues including alveolar bone and cementum.

Gingival Mesenchymal Stem Cells: A Periodontal Regenerative Substitute.

Gingival mesenchymal stem cells (GMSCs) are distinctive homogenous subset of mesenchymal stem cells (MSCs), which has its development from neural ectomesenchyme along with contributions from the perifollicular mesenchyme and the dental follicle proper. GMSCs stand apart from other dental MSCs owing to their ease of accessibility and availability with incredible long culture sustainability without any tumorigenic capability, and stable telomerase activity. Their capacity to differentiate into various cell lineages and inherent therapeutic effect in chronic inflammatory diseases like colitis, rheumatoid arthritis, systemic lupus erythematous (SLE) and diabetes makes them immensely valuable. The immunomodulatory and anti-inflammatory properties aid its usage in auto immune diseases and graft versus host disease. However, the differentiation, immunomodulatory and anti-inflammatory effects of GMSCs in periodontal tissue regeneration are less explored. In this review article, we have comprehensively compiled and described several reports on GMSCs till date, including their basic properties and isolation protocols, subpopulations, spheroid GMSCs, gingiva-derived IPSCsinduced pluripotent stem cells (iPSCs), their characterization, multilineage differentiation, and immunomodulatory properties along with precise applications in periodontal regeneration and peri-implantitis. Though the studies on GMSCs in periodontal regeneration lack superior quality random clinical trials, this review article still strengthens the view that GMSCs can be a newer source in periodontal tissue reconstruction/regeneration.

Effectiveness of amine plasma-functionalized 3D PLGA scaffolds immobilized with Fibroblast Growth Factor in periodontal tissue regeneration

Polylactic-co-glycolic acid (PLGA) has widely been used as a biodegradable material for three-dimensional (3D) printed scaffolds. However, the lack of surface chemicals and poor wettability limit the application of the polymer. Therefore, we modified the 3D scaffold surface using plasma surface modifications and evaluated its biocompatibility. To introduce amine functional groups on the 3D PLGA scaffold surface, amine plasma-polymerization was performed using 1, 2-diaminocyclohexane (DACH) monomers. Then, Fibroblast Growth Factor (FGF) was immobilized on the amine-functionalized 3D PLGA scaffold surface using a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. Human Gingival Fibroblast (HGF-1) cell behaviors were evaluated through cell adhesion, migration, proliferation, and western blot. The results showed that DACH plasma-polymerization provided the amine-functionalized surface which is capable of immobilizing FGF bioactive molecules on the 3D PLGA scaffold. Cell adhesion, proliferation, and migration on plasma surface-modified scaffolds have greatly improved compared to pristine 3D PLGA scaffolds. Notably, FGF-immobilized groups demonstrated the highest proliferation. These results suggest that the FGF-immobilized scaffold surface had a significant effect on accelerating oral gingival cell proliferation. In the future, 3D PLGA scaffolds with surface functionalized by plasma-polymerization and biomolecule immobilization can be used as a good alternative to autogenous soft tissue grafts for damaged soft tissue restoration.

Comparative Evaluation of Cone Beam Computed Tomography and Surgical Measurements of Periodontal Bone Defects in Periodontitis Patients: An In Vivo Study.

The present study aimed to evaluate the accuracy of noninvasive cone beam computed tomography (CBCT) in the estimation of periodontal bone defects and compare it with that of measurements obtained by invasive surgical exploration using open flap debridement procedure for the evaluation of bony topography. Bone defects in 384 sites with moderate-to-severe periodontitis from eight patients were considered. Probing depth was measured in the following six sites in the selected teeth: mesiobuccal (MB), mesiopalatal (MP)/mesiolingual (ML), buccal (B), palatal (P)/lingual (L), distobuccal (DB) and distopalatal (DP)/distolingual (DL). The bone defects were measured from CBCT images followed by surgical intervention at all six sites. Data were recorded and statistically analyzed. There was no significant difference observed between CBCT and surgical intervention. However, surgical intervention was found to have higher mean values than the CBCT measurements. The Pearson correlation showed a significantly positive correlation (p < 0.05) between CBCT and surgical intervention in all sites except L/P site. Additionally, there were negative correlations observed for all sites except B and L/P sites; however, these were not statistically significant. Moreover, there were significant differences (p < 0.05) observed between anterior and posterior sites measured via CBCT except for the MB site. On the other hand, a comparison between anterior and posterior teeth measured via surgical interventions showed significant differences (p = 0.0001) in all measured sites. A significant correlation has been observed between measurements acquired from CBCT and surgical intervention for the anterior teeth. On the contrary, no significant correlation was observed for the posterior teeth. Overlapping and the absence of 3D information are two of traditional radiography's main drawbacks. Surgerical exposure can yield precise information, but it gives less time to plan the kind of periodontal regeneration that will be needed. The accuracy and feasibility of CBCT have been established. How to cite this article: Alzahrani E, Soman C, Alasqah M, et al. Comparative Evaluation of Cone Beam Computed Tomography and Surgical Measurements of Periodontal Bone Defects in Periodontitis Patients: An In Vivo Study. J Contemp Dent Pract 2024;25(8):772-777.

KDM6B-Mediated HADHA Demethylation/Lactylation Regulates Cementogenesis.

Cementum, a bone-like tissue, is an essential component of periodontium, and periodontitis can lead to degenerative changes in the cementum, eventually resulting in tooth loss. The therapeutic strategy for advanced periodontitis is to achieve periodontal regeneration, of which cementum regeneration is a key criterion. Cementoblasts are responsible for cementogenesis, and their mineralization counts in cementum regeneration. However, research is still limited. Thus, novel treatment targets are required. The expression levels of lysine (K)-specific demethylase 6B (KDM6B), fatty acid oxidation (FAO), and cementogenic markers were detected by quantitative polymerase chain reaction, Western blot, immunofluorescence, and immunohistochemical assays. FAO levels were analyzed by assay kit. In vivo, injection of GSK-J4 into mice detected the influence of KDM6B on cementum formation. Chromatin immunoprecipitation sequencing, transcriptomic RNA sequencing, subsequent chromatin immunoprecipitation-quantitative polymerase chain reaction and overexpression of HADHA (hydroxyacyl-coA dehydrogenase trifunctional multienzyme complex subunit alpha) elucidated the KDM6B-Hadha axis. Global lactylation was detected by Western blot. Lactylation proteomics clarified the modified sites of HADHA. Mutating these sites and applying coimmunoprecipitation confirmed their significance. Knockdown of Kdm6b was utilized to assess its regulation on the lactylation of HADHA, FAO, and mineralization levels. FAO and KDM6B expression was elevated during cementoblast mineralization. KDM6B targeted Hadha and activated its transcription, thereby increasing FAO levels and promoting mineralization. Lactylation occurred in the process of mineralization, and KDM6B could regulate the lactylation of HADHA to promote FAO and mineralization. Overexpression of Hadha and the addition of lactate sodium could rescue the inhibition of mineralization by knockdown of Kdm6b. In summary, during cementoblast mineralization, KDM6B regulates HADHA by mediating histone demethylation and lactylation, thereby upregulating FAO and thus promoting mineralization.

Impact of Hyaluronic Acid and Other Re-Epithelializing Agents in Periodontal Regeneration: A Molecular Perspective.

This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms.

Prospective and challenges of locally applied repurposed pharmaceuticals for periodontal tissue regeneration.

Periodontitis is a persistent inflammatory condition that causes periodontal ligament degradation, periodontal pocket development, and alveolar bone destruction, all of which lead to the breakdown of the teeth's supporting system. Periodontitis is triggered by the accumulation of various microflora (especially anaerobes) in the pockets, which release toxic substances and digestive enzymes and stimulate the immune system. Periodontitis can be efficiently treated using a variety of techniques, both regional and systemic. Effective therapy is dependent on lowering microbial biofilm, minimizing or eradicating pockets. Nowadays, using local drug delivery systems (LDDSs) as an adjuvant therapy to phase I periodontal therapy is an attractive option since it controls drug release, resulting in improved efficacy and lesser adverse reactions. Choosing the right bioactive agent and mode of delivery is the foundation of an efficient periodontal disease management approach. The objective of this paper is to shed light on the issue of successful periodontal regeneration, the drawbacks of currently implemented interventions, and describe the potential of locally delivered repurposed drugs in periodontal tissue regeneration. Because of the multiple etiology of periodontitis, patients must get customized treatment with the primary goal of infection control. Yet, it is not always successful to replace the lost tissues, and it becomes more challenging as the defect gets worse. Pharmaceutical repurposing offers a viable, economical, and safe alternative for non-invasive, and predictable periodontal regeneration. This article clears the way in front of researchers, decision-makers, and pharmaceutical companies to explore the potential, effectiveness, and efficiency of the repurposed pharmaceuticals to generate more economical, effective, and safe topical pharmaceutical preparations for periodontal tissue regeneration.

The Effect of Platelet-Rich Fibrin (PRF) in Accelerating Periodontal Regeneration: A Randomized Controlled Clinical Trial

ABSTRACT Background: Regeneration of periodontal tissues is an essential component in treating periodontal disease, and there is an increasing focus on biological agents that might improve the healing process. Materials and Methods: The randomized controlled clinical study included a cohort of 60 individuals diagnosed with chronic periodontitis. Each participant was randomly allocated to one of two groups: the experimental group (n = 30), which underwent PRF in combination with traditional open flap debridement (OFD), and the control group (n = 30), which received OFD alone. Clinical criteria such as probing pocket depth (PPD), clinical attachment level (CAL), and bone fill percentage were assessed at baseline and after 6 months. Furthermore, cone-beam computed tomography (CBCT) was used to evaluate bone regrowth radiographically. Results: Following a period of 6 months, the experimental group had a notable decrease in postpartum depression (mean decrease of 4.2 mm) and an increase in central artery ligation (mean increase of 3.5 mm) compared to the control group, which had a mean decrease in postpartum depression of 2.8 mm and a mean increase in central artery ligation of 2.1 mm. The test group had a notably greater proportion of bone fill (45%) in comparison to the control group (30%). Further radiographic study verified enhanced bone regeneration in the areas treated with PRF. Conclusion: The use of Platelet-Rich Fibrin (PRF) in combination with traditional periodontal surgery greatly expedites the process of periodontal regeneration, as shown by notable enhancements in clinical indicators and bone regeneration.

ApoEVs Transfer Mitochondrial Component to Modulate Macrophages in Periodontal Regeneration.

Macrophages are key players in the host immune response to periodontal pathogens and tissue repair. The aim of this study was to explore the potential of apoptotic cell-derived extracellular vesicles (ApoEVs) in modulating the mitochondrial function of macrophages as a mean to enhance periodontal tissue regeneration. ApoEVs were extracted from periodontal ligament stem cells (PDLSCs) and characterized to observe their effects on macrophage function. Invivo experiments, ApoEVs were mixed with hyaluronic acid and injected into the periodontal pockets of rats with periodontitis to observe their impact on periodontal tissue regeneration and the immune microenvironment. Functional assays were conducted to confirm whether ApoEVs contained mitochondrial components and which specific components were transferred to regulate macrophage function. The experimental findings showed that treatment of ApoEVs efficiently restored the homeostasis of macrophage and improved tissue regeneration in a periodontitis rat model. Mechanism investigation demonstrated that the efferocytosis of ApoEVs resulted in the transfer of mitochondrial components from PDLSCs to macrophage. The increased mitochondrial components within macrophages improved mitochondrial function and polarization of macrophages towards the anti-inflammatory M2 phenotype, resulting in the improvement of inflammatory environment in periodontal tissues. ApoEVs can transfer mtDNA to enhance mitochondrial function in macrophages, fostering their transition to an anti-inflammatory phenotype. Ultimately, this process improves the immune microenvironment in periodontitis and promotes periodontal tissue regeneration.

Plasma Rich in Growth Factors Compared to Xenogenic Bone Graft in Treatment of Periodontal Intra-Osseous Defects-A Prospective, Comparative Clinical Study.

Periodontal intra-bony defects are challenging conditions in dental practice, often requiring regenerative approaches for successful treatment. This clinical study aimed to compare the effectiveness of plasma rich in growth factors (PRGF) versus xenogenic bone graft (BXG) in addressing intra-bony defects. Forty patients aged between 30 and 50 years presenting with generalized periodontitis were included. The study assessed various parameters, including relative attachment level (RAL); probing pocket depth (PPD); gingival marginal level (GML); intra-bony defect depth (IBDD) at baseline, 3, and 6 months; and level of pain, post-operative bleeding, and swelling, as patient-reported outcomes during the first seven days post operation. The results revealed that both PRGF and BXG treatments led to significant reductions in IBDD over the 6-month study period. PRGF demonstrated significant advantages in GML enhancement and post-operative pain management during the initial post-treatment days. However, BXG showed a significantly greater reduction in IBDD compared to PRGF. Post-operative bleeding and swelling levels were comparable between the two treatments. These findings underscore the efficacy of both PRGF and BXG in periodontal regeneration, with treatment decisions guided by patient-specific factors and clinical goals.

Enamel matrix derivative in the treatment of tooth replantation: from a biological basis to clinical application

Background An efficient therapeutic strategy for patients with replanted teeth has been extremely challenging because complete displacement of the teeth is inevitably accompanied by severe damage to periodontal tissue. Enamel matrix derivative (EMD) shows promise for periodontal regeneration, but its effects on replanted teeth remain unknown. This study systematically summarized the biological basis of EMD in replantation dental therapy and assessed its effect on clinical prognosis. Methods Potential studies were searched via the Cochrane Library, Web of Science and PubMed databases from inception to November 23, 2023. Results A total of 329 patients with 375 replanted teeth met the inclusion criteria. Our pooling results indicated that EMD did not provide a numerical advantage for restoring normal PDL healing in replanted teeth (RR=0.38, P=0.161). A significantly lower extraction risk was observed in EMD-treated group than non-EMD-treated group (RR=0.47, P=0.001). Moreover, the survival rate of replanted teeth with root resorption was significantly increased by the application of EMD (RR=2.21, P=0.017). Although the pooled outcomes suggested increased incidence of surface resorption (RR=1.19, P=0.730) and decreased risk of inflammation resorption (RR=0.68, P=0.560) among replanted teeth with resorption in the EMD-treated group, neither difference was statistically significant. Conclusion For patients with replanted teeth, EMD treatment may not result in a numerical increase in normal PDL healing. However, as a biological regulator, EMD may arrest the progression of resorption, thus reducing the risk of extraction in the early stage. Well-designed randomized trials are required to validate these results due to the poor quality of evidence.

Establishment of Periodontal Ligament Stem Cell-like Cells Derived from Feeder-Free Cultured Induced Pluripotent Stem Cells.

The periodontal ligament (PDL) is a fibrous connective tissue that connects the cementum of the root to the alveolar bone. PDL stem cells (PDLSCs) contained in the PDL can differentiate into cementoblasts, osteoblasts, and PDL fibroblasts, with essential roles in periodontal tissue regeneration. Therefore, PDLSCs are expected to be useful in periodontal tissue regeneration therapy. In a previous study, we differentiated induced pluripotent stem cells (iPSCs) into PDLSC-like cells (iPDLSCs), which expressed PDL-related markers and mesenchymal stem cell (MSC) markers; they also exhibited high proliferation and multipotency. However, the iPSCs used in this differentiation method were cultured on mouse embryonic fibroblasts; thus, they constituted on-feeder iPSCs (OF-iPSCs). Considering the risk of contamination with feeder cell-derived components, iPDLSCs differentiated from OF-iPSCs (ie, OF-iPDLSCs) are unsuitable for clinical applications. In this study, we aimed to obtain PDLSC-like cells from feeder-free iPSCs (FF-iPSCs) using OF-iPDLSC differentiation method. First, we differentiated FF-iPSCs into neural crest cell-like cells (FF-iNCCs) and confirmed that FF-iNCCs expressed NCC markers (eg, Nestin and p75NTR). Then, we cultured FF-iNCCs on human primary PDL cell-derived extracellular matrix for 2 weeks; the resulting cells were named FF-iPDLSCs. FF-iPDLSCs exhibited higher expression of PDL-related and MSC markers compared with OF-iPDLSCs. FF-iPDLSCs also demonstrated proliferation and multipotency in vitro. Finally, we analyzed the ability of FF-iPDLSCs to form periodontal tissue invivo upon subcutaneous transplantation with β-tricalcium phosphate scaffolds into dorsal tissues of immunodeficient mice. Eight weeks after transplantation, FF-iPDLSCs had formed osteocalcin-positive bone/cementum-like tissues and collagen 1-positive PDL-like fibers. These results suggested that we successfully obtained PDLSC-like cells from FF-iPSCs. Our findings will contribute to the development of novel periodontal regeneration therapies.

A Pt@ZIF-8/ALN-ac/GelMA composite hydrogel with antibacterial, antioxidant, and osteogenesis for periodontitis

Periodontitis is a chronic inflammatory disease caused by oral pathogens, and the osteogenic potential of human periodontal ligament stem cells (hPDLSCs) is severely impaired under the inflammatory environment. Current clinical periodontitis treatment strategies such as surgical interventions and antibiotic delivery still suffer from poor antibacterial efficacy, difficulty in ameliorating excessive inflammatory responses and slow periodontal tissue regeneration. Here, we have innovatively developed a non-surgical treatment strategy based on a functional composite hydrogel. A composite hydrogel system (Pt@ZIF-8/ALN-ac/Gel) containing bioactive zeolite imidazolate framework-8 (ZIF-8) integrated with platinum nanoparticles (Pt@ZIF-8) and alendronate acrylamide (ALN-ac) was constructed on the basis of gelatin methacryloyl (GelMA) to achieve enhanced antibacterial effect and reactive oxygen species (ROS) scavenging ability while promoting the osteogenic potential of hPDLSCs. We confirmed that Pt@ZIF-8/ALN-ac/Gel was able to continuously release Zn2+ and exerted an obvious antibacterial effect against Porphyromonas gingivalis. In vitro experiments proved that Pt@ZIF-8/ALN-ac/Gel had good biocompatibility, while efficiently featuring excellent reactive oxygen species (ROS) scavenging capacity, increasing alkaline phosphatase activity, and promoting extracellular matrix mineralization by hPDLSCs. In vivo, Pt@ZIF-8/ALN-ac/Gel significantly inhibited the alveolar bone deterioration and reduced osteoclast activation and inflammation, thereby promoting the regeneration of damaged tissues. These findings demonstrated superior therapeutic efficacy in the reported clinical periodontitis treatment, exhibiting great potential for application.

The efficacy of infrared diode laser in enhancing the regenerative potential of human periodontal ligament stem cells (hPDLSCs)

BackgroundThe present study aimed to investigate the effects of infrared diode laser irradiation on the proliferation and differentiation capacity of periodontal ligament stem cells (hPDLSCs), which are optimal cell sources for periodontal regeneration.MethodshPDLSCs were isolated and characterized by flow cytometric analysis of mesenchymal stem cell markers, and their trilineage differentiation capacity was tested. hPDLSCs were then cultured and irradiated with infrared diode laser (970 nm) at a power of 200 mW and a fluence of 4 J/cm2 for 3 s. MTT assay was performed to assess cellular proliferation. Cell cycle analysis was performed, and the impact of infrared diode laser irradiation on the stemness and osteogenic differentiation potential of hPDLSCs was evaluated via RT‒PCR.ResultsInfrared diode laser application enhanced the stemness, viability, proliferation, and differentiation of PDLSCs. Stem cell markers (OCT4, SOX2, and NANOG) were significantly upregulated in hPDLSCs exposed to laser irradiation. There was significant overexpression of RUNX2, ALP, OPN, and OCN on day 14 after laser application.ConclusionsThese findings provide valuable insights into the specific applications of infrared diode lasers to effectively regenerate periodontal tissues. The results can aid in the development of precise clinical protocols aimed at enhancing osseointegration and promoting tissue regeneration. Ultimately, the combination of infrared diode laser with hPDLSCs is promising for stimulating periodontal regeneration.

Preclinical Evaluation of a Poly (Lactic Acid/Caprolactone) Bilayer Membrane and a Carbonate Apatite for Periodontal Regeneration: A Canine One-Wall Intrabony Defect Model.

This preclinical study aimed to evaluate the periodontal tissue regenerative capacities of poly (lactic acid/caprolactone) (PLCL) bilayer membrane in one-wall intrabony defects in dogs. No study has assessed the efficacy of PLCL bilayer membrane for periodontal regeneration therapy despite the fact that PLCL bilayer membrane has proved efficient for bone regeneration. In five beagle dogs, the bilateral mandibular second and fourth premolars were extracted 8 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 6 mm in width) were surgically created on the mesial and distal roots of the bilateral third premolars in the mandible. The test groups were set up as follows: (i) carbonate apatite (CO3Ap) + PLCL, (ii) CO3Ap, (iii) xenograft (DBBM) + collagen membrane (CM), and (iv) DBBM. The control group was left empty. Radiological, histologic and histomorphometric characteristics were compared 8 weeks after surgery. No infectious complications were detected at any of the tested sites. The test groups exhibited a greater height and volume of the newly formed bone than the control group. They also showed a greater height of the newly formed cementum than the control group. However, the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the test groups. The combined use of PLCL bilayer membrane and CO3Ap demonstrated comparable performance for periodontal tissue regeneration in one-wall intrabony defects compared to conventional therapies.

Synthetic Periodontal Guided Tissue Regeneration Membrane with Self-Assembling Biphasic Structure and Temperature-Sensitive Shape Maintenance.

Periodontal disease poses significant challenges to the long-term stability of oral health by destroying the supporting structures of teeth. Guided tissue regeneration techniques, particularly barrier membranes, enable local regeneration by providing an isolated, protected compartment for osseous wound healing while excluding epithelial tissue. Here, this study reports on a thermosensitive periodontal membrane (TSPM) technology designed to overcome the mechanical limitations of current membranes through a semi-interpenetrating network of high molecular weight poly(L-lactic acid) (PLLA) and in situ-polymerized mesh of poly(ε-caprolactone)diacrylate (PCL-DA), and poly lactide-co-glycolide diacrylate (PLGA-DA). An optimized composition allows facile reshaping at greater than 52 °C and rigid shape maintenance at physiological temperature. Its unique bilayer morphology is achieved through self-assembly and thermally-induced phase separation, resulting in distinct yet continuous smooth and nanofibrous compartments adequate for epithelial occlusion and regeneration. Incorporating PLGA-DA enhances the membrane's hydrophilicity and degradation properties, facilitating a more rapid and controlled degradation and therapeutic delivery. This study demonstrates its ability to promote local regeneration by serving as a barrier membrane and simultaneously as a scaffolding matrix in a rat orthotopic periodontal defect model. The TSPM outperformed a clinically available material (Epi-Guide) to facilitate robust alveolar bone and periodontal ligament regeneration at 4 and 8 weeks.

Polyphenol-mediated redox-active hydrogel with H2S gaseous-bioelectric coupling for periodontal bone healing in diabetes.

Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabeticperiodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. Theslow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.