Periodontal Regeneration Research Articles

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.

Autogenous platelet concentrates for treatment of intrabony defects-A systematic review with meta-analysis.

To provide an overview of the use of autogenous platelet concentrates (APCs) in periodontal regeneration and to conduct a systematic review (SR) of the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) compared with other commonly utilized modalities. The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 21 categories and into five different groups as follows: Group I (1) open flap debridement (OFD) alone versus OFD/PRF, (2) OFD versus Titanium-PRF (T-PRF) Group II, (3) Comparative PRF protocols (PRF vs. T-PRF), Group III (Comparative Studies to PRF): (4) OFD/PRP versus OFD/PRF, (5) OFD/bone graft(BG)/PRGF versus OFD/BG/PRF, (6) OFD/EMD versus OFD/PRF, (7) OFD/BG/EMD versus OFD/BG/PRF, (8) OFD/collagen membrane (CM) versus OFD/PRF, (9) OFD/BG/BM versus OFD/BG/PRF, (10) OFD/BG versus OFD/PRF, Group IV (Addition of PRF to treatment groups) (11) OFD/BG versus OFD/BG/PRF, (12) OFD/GTR versus OFD/GTR + PRF (13) OFD/EMD versus OFD/EMD/PRF (14) OFD/BG/BM versus OFD/BG/BM/PRF, Group V (Addition of Biomaterial/Biomolecule to PRF): OFD/PRF versus … (15) OFD/PRF/BG, (16) OFD/PRF/antibiotic, (17) OFD/PRF/Metformin, (18) OFD/PRF/Bisphosphonates, (19) OFD/PRF/Statins, (20) OFD/BG/PRF versus OFD/BG/PRF/Statins, and (21) OFD/PRF/low-level laser therapy (LLLT). Weighted means and forest plots were calculated for probing pocket depth (PPD), clinical attachment level (CAL), and radiographic bone fill (RBF). From 596 records identified, 55 RCTs were included. Group I: The use of OFD/PRF statistically significantly reduced PPD and improved CAL and RBF when compared to OFD. Group II: A significant difference between various PRF protocols was only observed for PPD. Group III: No significant advantage was found when comparing OFD/PRF to the following groups: OFD/PRP, OFD/EMD, OFD/BM, or OFD/BG. Group IV: The addition of PRF to OFD/BG led to significant improvements in PPD, CAL and RBF compared with OFD/BG alone. Group V: The addition of either a BG as well as three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements in PPD, CAL, and/or RBF when compared to OFD/PRF alone. The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone. Similar results were observed when OFD/PRF was compared with OFD/BG, OFD/EMD, OFD/PRP, and OFD/BM. The addition of PRF to a bone grafting material as well as the addition of various small biomolecules to PRF may offer additional clinical advantages, thus warranting further investigations. Future research investigating various protocols of PRF, longer-term outcomes, as well as PRF at the human histological level remains needed.

A Contemporary Approach: Presentation of 4 Cases with the Entire Papilla Preservation (EPP) Technique

Regeneration of periodontal tissue is a primary goal of periodontal treatment. Periodontal regeneration approaches are widely used in the treatment of intraosseous defects. However, the success of these techniques depends on many factors, including surgical considerations. Failures in wound closure in the interdental region, which are surgical factors, have led to the development of papilla preservation techniques. The entire papilla preservation technique (EPP) maintains the integrity of the papilla associated with the defect. This technique stabilizes the blood clot with intact gingiva, preventing wound exposure and contamination. EPP is performed in intra-osseous defects through a short buccal vertical incision, without incising the papilla of the involved tooth. A full-thickness buccal flap is lifted from the incision to the relevant papilla and a tunnel extending under the papilla is prepared. The papilla is also lifted to full thickness. The defect is cleaned of granulation tissue and the wound is closed primarily with or without biomaterial application. In this report, we present 4 cases, 3 in the anterior maxilla and 1 in the mandibular premolar region, undergoing periodontal surgery with EPP with biomaterial application with a 3-month follow-up. In all cases, soft tissue healing was uncomplicated and radiographs showed bone filling at 3 months. EPP has a high success rate in periodontal regeneration by providing complete nutrition of the interdental papilla through natural, continuous vascular support in intraosseous defects.

Stem Cells: Present Understanding and Prospects for Regenerative Dentistry.

Regenerative medicine in dentistry focuses on repairing damaged oral tissues using advanced tools like stem cells, biomaterials, and tissue engineering (TE). Mesenchymal stem cells (MSCs) from dental sources, such as dental pulp and periodontal ligament, show significant potential for tissue regeneration due to their proliferative and differentiative abilities. This systematic review, following PRISMA guidelines, evaluated fifteen studies and identified effective strategies for improving dental, periodontal, and bone tissue regeneration through scaffolds, secretomes, and bioengineering methods. Key advancements include the use of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) to boost cell viability and manage inflammation. Additionally, pharmacological agents like matrine and surface modifications on biomaterials improve stem cell adhesion and promote osteogenic differentiation. By integrating these approaches, regenerative medicine and TE can optimize dental therapies and enhance patient outcomes. This review highlights the potential and challenges in this field, providing a critical assessment of current research and future directions.

Response of a Blood Clot Adherent to Bone, Oral Mucosa and Hard Dental Tissues to a Uniaxial Tensile Test: An In Vitro Study.

Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such as tooth root, mucosa and bone needs to be stable, which is a reason why the treatment of non-containing periodontal bone defects, in which the clot may undergo displacement, is challenging. The gingival soft tissue, properly sutured, may act as a wall for blood clot stabilization. Knowledge on the response of the blood clot to stress and how it might vary according to the characteristics of the tissues it gets in contact with might be deepened. The aim of this study was to investigate in vitro, by means of a micro-loading device, the response of the complex formed by a blood clot and diverse tissues, simulating those involved in periodontal regeneration, to a displacing tensile test. Materials and Methods: Experimental samples made of two layers of either hard dental tissues, cancellous bone or oral mucosa, between which fresh blood was interposed, underwent a debonding experiment by means of a micro-loading device that measured their response to uniaxial tensile stress. Results: The peak of tensile stress and the overall work needed for the complete rupture of the clot's fibrin filaments were significantly higher for hard dental tissues than for other tissues. However, mucosa sustained the highest maximal strain in terms of relative displacement between the plates of the micro-loading device to accomplish the complete rupture of the fibrin filaments compared to the other tissues, suggesting that the mucosa might act as a stable interface with the clot and be able to sustain tensile stresses. Conclusions: This in vitro study seems to support the use of mucosa to act as a wall for regenerative procedures of suprabony periodontal defects given its capability to form a stable interface with the clot.

Periodontal ligament stem cell tissue engineering scaffolds can guide and promote canine periodontal tissue regeneration.

The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect. In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained. The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site. New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.

The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials.

Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.

Mesenchymal stem cell-derived protein extract induces periodontal regeneration: MSC-protein induces periodontal regeneration

BackgroundPeriodontal disease is characterized by chronic inflammation and destruction of supporting periodontal tissues, ultimately leading to tooth loss. In recent years, “cell-free treatment” without stem cell transplantation has attracted considerable attention for tissue regeneration. This study investigated the effects of extracts of mesenchymal stem cells (MSC-extract) and their protein components (MSC-protein) on the proliferation and migration of periodontal ligament (PDL) cells and whether MSC-protein can induce periodontal regeneration. MethodsMSC-extract and MSC-protein were obtained by subjecting mesenchymal stem cells (MSCs) to freeze–thaw cycles and acetone precipitation. Cell proliferation was examined using a WST-8 assay and Ki67 immunostaining, and cell migration was examined using Boyden chambers. The MSC-protein content was analyzed using liquid chromatography-mass spectrometry, protein arrays, and enzyme-linked immunosorbent assays (ELISAs). Gene expression in MSC-protein-treated PDL cells was examined using RNA-sequencing and Gene Ontology analyses. The regenerative potential of MSC-protein was examined using micro-computer tomography (CT) and histological analyses after transplantation into a rat periodontal defect model. ResultsMSC-extract and MSC-protein promoted the proliferation and migration of PDL cells. Protein array and ELISA revealed that MSC-protein contained high concentrations of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Exogenous bFGF promoted the proliferation and migration of PDL cells. Furthermore, the transplantation of MSC-protein enhanced periodontal tissue regeneration with the formation of new alveolar bone and PDLs. ConclusionsThese results indicate that the MSC-protein promotes the proliferation and migration of PDL cells and induces significant periodontal tissue regeneration, suggesting that the MSC-protein could be used as a new cell-free treatment for periodontal disease.

Hierarchically structured nanofibrous scaffolds spatiotemporally mediate the osteoimmune micro-environment and promote osteogenesis for periodontitis-related alveolar bone regeneration

Periodontitis suffer from inflammation-induced destruction of periodontal tissues, resulting in the serious loss of alveolar bone. Controlling inflammation and promoting bone regeneration are two crucial aspects for periodontitis-related alveolar bone defect treatment. Herein, we developed a hierarchically structured nanofibrous scaffold with a nano-embossed sheath and a bone morphogenetic protein 2-loaded core to match the periodontitis-specific features that spatiotemporally modulated the osteoimmune environment and promoted periodontal bone regeneration. We investigated the potential of this unique scaffold to treat periodontitis-related alveolar bone defects in vivo and in vitro. The results demonstrated that the hierarchically structured scaffold effectively reduced the inflammatory levels in macrophages and enhanced the osteogenic potential of bone mesenchymal stem cells in an inflammatory microenvironment. Moreover, in vivo experiments revealed that the hierarchically structured scaffold significantly ameliorated inflammation in the periodontium and inhibited alveolar bone resorption. Notably, the hierarchically structured scaffold also exhibited a prolonged effect on promoting alveolar bone regeneration. These findings highlight the significant therapeutic potential of hierarchically structured nanofibrous scaffolds for the treatment of periodontitis, and their promising role in the field of periodontal tissue regeneration. Statement of Significance: We present a novel hierarchically structured nanofibrous scaffold of coupling topological and biomolecular signals for precise spatiotemporal modulation of the osteoimmune micro-environment. Specifically, the scaffold was engineered via coaxial electrospinning of the poly(ε-caprolactone) sheath and a BMP-2/polyvinyl alcohol core, followed by surface-directed epitaxial crystallization to generate cyclic nano-lamellar embossment on the sheath. With this unique hierarchical structure, the cyclic nano-lamellar sheath provided a direct nano-topographical cue to alleviate the osteoimmune environment, and the stepwise release of BMP-2 from the core provided a biological cue for bone regeneration. This research underscores the potential of hierarchically structured nanofibrous scaffolds as a promising therapeutic approach for periodontal tissue regeneration and highlights their role in advancing periodontal tissue engineering.

Development and characterization of nitazoxanide-loaded poly(ε-caprolactone) membrane for GTR/GBR applications

ObjectiveGuided tissue/guided bone regeneration (GTR/GBR) membranes are widely used for periodontal bone regeneration, but their success depends on a bacteria-free environment. Systemic antibiotic treatment often proves inadequate, moreover, the increasing prevalence of antibiotic resistance in oral infections exacerbates this challenge. This study aimed to fabricate antibacterial membranes using a new class of antibiotics for local drug delivery, to eradicate infections and promote tissue regeneration. MethodsMembranes loaded with nitazoxanide (NTZ) were fabricated via electrospinning using poly(ε-caprolactone) (PCL) with varying concentrations of NTZ (0 %, 2.5 %, and 5 % w/w) relative to the polymer weight. Morphochemical of NTZ-loaded membranes were assessed using scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and Fourier Transform Infrared spectroscopy (FTIR). Mechanical properties were evaluated using universal testing machine and NTZ release profile from membranes was determined by spectrophotometer (λmax = 444) for 14 days. Antimicrobial efficacy against periodontal pathogens, cell compatibility and mineralization were evaluated using periodontal ligament stem cells (PDLSCs). ResultsOptimized spinning parameter maintained a uniform fiber diameter and successful loading of NTZ was confirmed by SEM-EDS and FTIR. NTZ incorporation did not significantly affect mechanical properties, whereas the drug release kinetics showed an initial burst, followed by sustained release over 14 days. NTZ-loaded membranes demonstrated antibacterial activity against Aggregatibacter actinomycetemcomitans (Aa) and Fusobacterium nucleatum (Fn). Importantly, the presence of NTZ showed minimal cell toxicity; however, it reduced the mineralization potential compared with that of the pure PCL membrane, which increased over time. SignificanceTaken together, these findings established that NTZ-loaded membranes could be promising barrier membrane to counteract microbial environment and aid periodontal bone regeneration.

Impact of Polydeoxyribonucleotides on the Morphology, Viability, and Osteogenic Differentiation of Gingiva-Derived Stem Cell Spheroids

Background and Objectives: Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods: Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results: The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions: In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations.

Low-energy red light-emitting diode irradiation enhances osteogenic differentiation of periodontal ligament stem cells by regulating miR-146a-5p.

The study aimed to investigate the role of miR-146a-5p in osteogenesis of hPDLSCs irradiated with low-energy red LEDs. After irradiation with 5 J/cm2 red LED, miR-146a-5p expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and osteogenic markers expression was determined by RT-qPCR and Western blotting. Alkaline phosphatase (ALP) activity was assessed by ALP staining, and mineralization was assessed by Alizarin Red staining, respectively. Lentiviral vectors were designed to regulate miR-146a-5p expression. Dual-luciferase reporter assay was performed to confirm the targeted relationship between miR-146a-5p and MAPK1. Short hairpin RNA (shRNA) was used to regulate MAPK1 expression. RT-qPCR and western blotting revealed that 5 J/cm2 irradiation elevated the levels of the osteogenic markers osterix (OSX) and bone sialoprotein (BSP) in hPDLSCs. miR-146a-5p is downregulated in hPDLSCs under the low-energy red LED light irradiation. miR-146a-5p underexpression markedly promoted the osteogenic potential of hPDLSCs. miR-146a-5p targeted MAPK1. 5 J/cm2 red LED irradiation rescued the inhibitory effects of upregulated miR-146a-5p on osteogenic differentiation, and the positive influence of red LED irradiation could be reversed by downregulated MAPK1. These findings confirm that miR-146a-5p is involved in the effect of LED irradiation on the osteogenic differentiation of hPDLSCs by targeting MAPK1. Red LED irradiation may be a potential clinical adjunct therapy for periodontal regeneration.

Success of Periodontal Regeneration in Molars with Intrabony Defect

Success of Periodontal Regeneration in Molars with Intrabony Defect

Papillary Coronal Anchorage Technique for Periodontal Reconstruction of Infrabony Defect and Interdental Papilla: A Case Report.

Esthetic issues and phonetic disturbances frequently occur after periodontal regeneration of the anterior teeth, even if treatment is supposed to be successful. Conventional regenerative techniques are predominantly targeted at infrabony defects and often inadequately address the loss of the interdental papilla. This study introduces the papillary coronal anchorage technique, a novel modified tunnel surgical procedure, to facilitate the reconstruction of the interdental papilla. This method allows for coronal movement of the entire interdental papilla without incisions at the papilla to facilitate primary wound healing. Using a combination of bone grafts and recombinant human fibroblast growth factor 2 and anchoring the tunnel-like flap coronally using sutures, we successfully achieved a reconstruction of the infrabony defects as well as the interdental papilla. The papillary coronal anchorage technique is effective as it enables the simultaneous reconstruction of both the infrabony defect and the interdental papilla.

Periodontal Regenerative Treatment of Hopeless Tooth with Wall Technique

Periodontal Regenerative Treatment of Hopeless Tooth with Wall Technique

Self-cascade ROS-trapping bioreaction system reverses stem cell oxidative stress fate for osteogenesis

eactive oxygen species (ROS) scavenging is essential for periodontal regeneration. However, the dynamic change of the applied materials within the ROS-rich environment and the residual oxidation products in the host highly impact periodontal regeneration. This study successfully constructs a bioreaction system via thiol-ene click chemistry, leveraging the high affinity of glutathione (GSH) for ROS to attract excess ROS to the crosslinking points. Two minutes after hydrogen peroxide (H2O2) treatment, the ROS level in the G8-0 hydrogel acutely decreases, reaching a 4.4% reduction within 10minutes, confirming the ROS-trapping efficacy. Through a ‘bait switch-on’ mechanism, hexagonal boron nitride (hBN) takes over the captured ROS and the oxidation products of pectin further drive the reduction reaction, ultimately restoring the extracellular environment. The self-cascade products, oxidized hBN, reshape the intracellular oxidative stress (OS) environment, achieving a synergistic extra- and intra-cellular treatment. The significantly high reduced to oxidized glutathione (GSH/GSSG) ratio in G8-10 hydrogel (~80%) illustrates a reversal of oxidative stress in bone marrow stem cells (BMSCs). On a molecular level, the bioreaction system inhibits the NF-κB pathway, promoting the expression of key antioxidant genes (Nqo1 and Nrf2) and osteogenic molecules (ALP and OCN), thereby reversing the detrimental effects of OS on BMSCs. In vivo application demonstrated the system’s strong redox-balancing and osteogenic capabilities in the periodontal inflammation environment. This novel antioxidant bioreaction system, characterized by self-cascade ROS-trapping and product utilization, offers innovative treatment strategies for tissue regeneration under conditions of excessive OS.

Hypoxia-inducible Factor 1α Contributes to Matrix Metalloproteinases 2/9 and Inflammatory Responses in Periodontitis.

Periodontitis is a prevalent condition characterized by inflammation and tissue destruction within the periodontium, with hypoxia emerging as a contributing factor to its pathogenesis. Hypoxia-inducible factor 1α (HIF-1α) has a crucial role in orchestrating adaptive responses to hypoxic microenvironments and has been implicated in various inflammatory-related diseases. Understanding the interplay between HIF-1α, matrix metalloproteinases (MMPs), and inflammatory responses in periodontitis could provide insights into its molecular mechanisms. We investigated the relationship between HIF-1α, MMP2, and MMP9 in gingival crevicular fluid (GCF) and periodontal ligament stem cells (PDLSCs) from periodontitis patients. The expression levels of HIF-1α, MMP2, MMP9, and inflammatory factors (IL-6, IL-1β, TNF-α) were assessed using enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Additionally, osteogenic differentiation of PDLSCs was identified by alkaline phosphatase activity. Significantly elevated levels of HIF-1α, MMP2, and MMP9 were observed in GCF of periodontitis patients compared to controls. Positive correlations were found between HIF-1α and MMP2/MMP9, as well as with IL-6, IL-1β, and TNF-α. Modulation of HIF-1α expression in PDLSCs revealed its involvement in MMP2/9 secretion and inflammatory responses, with inhibition of HIF-1α mitigating these effects. Furthermore, HIF-1α inhibition alleviated the reduction in osteogenic differentiation induced by inflammatory stimuli. Our findings elucidate the regulatory role of HIF-1α in MMP expression, inflammatory responses, and osteogenic differentiation in periodontitis. In conclusion, targeting HIF-1α signaling pathways may offer therapeutic opportunities for managing periodontitis and promoting periodontal tissue regeneration.

Antibacterial periodontal ligament stem cells enhance periodontal regeneration and regulate the oral microbiome

BackgroundThe transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration.MethodsWe isolated human PDLSCs from periodontal ligament of extracted teeth. Rats’ periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro.ResultsMicrobiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37.ConclusionsOur findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.