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The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effects of photobiomodulation therapy (PBMT) with 660 and 980 nm diode lasers on differentiation of periodontal ligament mesenchymal stem cells (PDLMSCs). In this in vitro, experimental study, PDLMSCs were obtained from the Iranian Genetic Bank and cultured in osteogenic medium. They were then subjected to irradiation of 660 and 980 nm diode lasers, and their viability was assessed after one, two, and three irradiation cycles using the methyl thiazolyl tetrazolium (MTT) assay. The cells also underwent DAPI staining, cell apoptosis assay by using the Annexin V/PI, Alizarin Red staining, and real-time polymerase chain reaction (PCR) for assessment of the expression of osteogenic genes. Data were analyzed by two-way ANOVA. The two laser groups had no significant difference in cell apoptosis according to the results of DAPI staining. Both laser groups showed higher cell viability in the MTT assay at 4 and 6 days compared with the control group. Annexin V/PI results showed higher cell viability in both laser groups at 4 days compared with the control group. Rate of early and late apoptosis was lower in both laser groups than the control group at 4 days. Necrosis had a lower frequency in 980 nm laser group than the control group on day 6. Alizarin Red staining showed higher cell differentiation in both laser groups after 3 irradiation cycles than the control group. The highest expression of osteopontin (OPN), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2) was noted in 660 nm laser group with 3 irradiation cycles at 14 days, compared with the control group. PBMT with 660 and 980 nm diode lasers decreased apoptosis and significantly increased PDLMSC differentiation after 3 irradiation cycles. [ABSTRACT FROM AUTHOR]

Background: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). Conclusions: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ. [ABSTRACT FROM AUTHOR]

Background: Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods: To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results: In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation. Conclusion: The xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

In the recent years, electroconductive scaffolds have shown promising capabilities in guided regeneration of electroactive tissues including nerve, heart muscle, bone, cartilage, and skin. Herein, the fabrication of a novel electroconductive poly (L‐lactic acid) (PLLA)/polyamidoamine (PAMAM) dendrimer nanofibrous scaffold containing graphene oxide (GO) nanosheets is described. The presence of PAMAM with amine terminal groups successfully aminolyzed PLLA. Interestingly, both PAMAM (5% w/w) and GO (0.5, 1, 2% w/w) not only contributed to reducing the fiber diameter, increasing the hydrophilicity and degradation rate, but also provided a nanocomposite scaffold with enhancement in electrical conductivity. By incorporating 1% w/w of GO, the nanocomposite scaffold exhibited optimized properties, including electrical conductivity (≈3.09 × 10−5 S m−1), crystallinity (≈ 47%), Young's modulus (≈16.95 MPa), as well as strength (≈1.58 MPa). This nanocomposite also demonstrated significant antibacterial activity of ≥ 90% against both gram‐positive and gram‐negative bacteria. Cellular assays confirmed acceptable cytocompatibility of the nanocomposite scaffolds containing GO and PAMAM, which can support the viability and proliferation of PC‐12 cells. In conclusion, the presence of GO nanosheets alongside PAMAM dendrimers can synergically promote the properties of the prepared nanofibrous mats which can be used as potential electroconductive scaffolds for guided tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: Guided bone regeneration (GBR) is a reliable technique used in vertical and horizontal bone defects. The posterior mandibular region is an area limited by anatomic constraints. The use of resorbable membranes with a cortical component could compensate for the lack of rigidity of resorbable membranes without the complications of non-resorbable membranes. The aim of this study was to evaluate the mean bone gains of a xenogeneic cortical membrane in horizontal and vertical bone defects in comparison with other membranes in the literature. Methods: A porcine cortical membrane was used to perform 7 GBR in the posterior mandibular region of five patients. Preoperative (T0) and six months postoperative (T1) cone beam computed tomography were superimposed to measure the horizontal and vertical bone gain. Implants were positioned at all sites, six months after GBR. Complications and bone resorption around the implants were also documented. Results: The mean horizontal and vertical bone gains were 3.83 ± 1.41 mm and 4.17 ± 1.86 mm, respectively. The analysis of repeatability was 0.997. As many as 40% of patients experienced pain refractory to analgesics. No exposure or infectious phenomenon was observed. Conclusions: This xenogeneic cortical membrane seemed to provide interesting results in the regeneration of horizontal and vertical bone defects. Comparative and prospective studies are necessary to validate the effectiveness of this membrane. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to retrospectively evaluate the 3-year radiographic outcomes of periodontal intrabony defects treated with non-surgical subgingival therapy (NST), assessing radiographic bone gain (RBG) through experimental digital software, named "Bone Defect Analysis (BDA)". Methods: The study included 17 intrabony defects in 14 patients. BDA software (version 1) was used on radiographs to calculate RBG (in %) and variations in defect angle (in °) between baseline (T0) and 3-year follow-up (T1). Soft tissue conditions were registered, reporting bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL). Defects were analyzed according to angles less (group A) or greater (group B) than 30°. Results: Nine and eight defects were, respectively, analyzed in groups A and B. Three years after treatment, an average RBG of 12.28% was found overall, with 13.25% and 10.11% for groups A and B, respectively (p = 0.28). Clinically, a mean CAL of 6.05 mm at T1 (from 10.94 mm at T0) was found, with 6.88 mm and 5.12 mm in groups A and B, respectively (p = 0.07). Conclusions: BDA software demonstrated predictability in the evaluation of bone variations after NST, revealing better clinical findings for intrabony defects with an initial smaller angle. [ABSTRACT FROM AUTHOR]

The periodontal tissue is made up of supporting tissues and among its functions, it promotes viscoelastic properties, proprioceptive sensors, and dental anchorage. Its progressive destruction by disease leads to the loss of bone and periodontal ligaments. For this reason, biomaterials are constantly being developed to restore tissue function. Various techniques are being used to promote regenerative dentistry, including 3D bioprinting with bioink formulations. This paper aims to review the different types of bioink formulations and 3D bioprinting techniques used in periodontal tissue regeneration. Different techniques have been formulated, and the addition of different materials into bioinks has been conducted, with the intention of improving the process and creating a bioink that supports cell viability, proliferation, differentiation, and stability for periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate alterations in the concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) within gingival crevicular fluid (GCF) extracted from the intrabony periodontal defect site before and after minimally invasive regenerative surgery, with or without supplemental laser application. The surgical procedure was performed using the modified minimally invasive surgical technique (M-MIST). Methods: Thirty-eight patients, each presenting with a single vertical defect, were randomly assigned to either the test (M-MIST + Er:YAG + Nd:YAG) or the control group (M-MIST). IL-8 and MMP-9 levels (primary outcomes of the study) were assessed prior to therapy, after 2 and 4 weeks, and 6 months following the surgical procedure by means of dedicated ELISA kits. Results: Both procedures were clinically effective as evidenced by probing depth (PD) reduction and clinical attachment level (CAL) gain at the 6-month follow-up. No statistical differences were observed in the levels of MMP-9 and IL-8 between the groups at any time point assessed. The changes in the level of MMP-9 and IL-8 over time were not statistically significant in any group. IL-8 was positively correlated with MMP-9 in the control group throughout the study and in the test group 2 weeks and 6 months post-op. Conclusions: Within the limitations of this study, the additional application of Er:YAG + Nd:YAG lasers alongside the M-MIST procedure did not enhance the clinical and biochemical treatment outcomes compared to M-MIST alone. [ABSTRACT FROM AUTHOR]

Objectives: Guided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences. Materials and Methods: Six commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real‐time polymerase chain reaction (PCR). Results: C. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real‐time PCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤.001) with the membranes having a textured surface exhibiting the highest count of 2680 × 104 cells/ml compared to the count of 707 × 104 cells/mL on those with a nontextured one (p ≤.001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 104 cells/ml (p ≤.05). Conclusion: The results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance. [ABSTRACT FROM AUTHOR]

Advanced periodontitis poses a significant threat to oral health, causing extensive damage and loss of both hard and soft periodontal tissues. While traditional therapies such as scaling and root planing can effectively halt the disease's progression, they often fail to fully restore the original architecture and function of periodontal tissues due to the limited capacity for spontaneous regeneration. To address this challenge, periodontal tissue engineering has emerged as a promising approach. This technology centers on the utilization of biomaterial scaffolds, which function as three-dimensional (3D) templates or frameworks, supporting and guiding the regeneration of periodontal tissues, including the periodontal ligament, cementum, alveolar bone, and gingival tissue. These scaffolds mimic the extracellular matrix (ECM) of native periodontal tissues, aiming to foster cell attachment, proliferation, differentiation, and, ultimately, the formation of new, functional periodontal structures. Despite the inherent challenges associated with preclinical testing, the intensification of research on biomaterial scaffolds, coupled with the continuous advancement of fabrication technology, leads us to anticipate a significant expansion in their application for periodontal tissue regeneration. This review comprehensively covers the recent advancements in biomaterial scaffolds engineered specifically for periodontal tissue regeneration, aiming to provide insights into the current state of the field and potential directions for future research. [ABSTRACT FROM AUTHOR]

Background: The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. Methods: D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn's test or the Bonferroni test for pairwise comparisons. Results: A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group. Conclusion: GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery. [ABSTRACT FROM AUTHOR]

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium. [ABSTRACT FROM AUTHOR]

The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL−1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram‐negative Porphyromonas gingivalis and Gram‐positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non‐inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near‐complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri‐implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation. [ABSTRACT FROM AUTHOR]

Introduction: Gingival recession is the exposure of the root surface of the tooth, characterised by the displacement of the gingival margin apically from the Cementoenamel Junction (CEJ). Various techniques have been suggested for treating recession, such as Free Gingival Graft (FGG), Connective tissue grafts, laterally or Coronally Advanced Flaps (CAF), and Guided Tissue Regeneration (GTR)-based procedures. Different membranes have been used for GTR, one of which is the amnion membrane. Aim: To evaluate root coverage using Coronally Advanced Flap (CAF) with and without amniotic membrane in the treatment of localised gingival recession. Materials and Methods: A randomised controlled trial was conducted at Pandit Deendayal Upadhyay Dental College and Hospital, Solapur, Maharashtra, India from March 2017 to February 2018. In this study, 30 teeth were treated, with 15 teeth undergoing CAF with amniotic membrane (Group IITest Group) and 15 teeth treated with CAF without amniotic membrane (Group I-Control Group). Probing Depth (PD), Clinical Attachment Level (CAL), Relative Attachment Level (RAL), Recession Width (RW), Recession Depth (RD), Width of Keratinised Gingiva (WKG), Width of Attached Gingiva (WAG), and gingival biotype were assessed between baseline and after three months. Statistical analysis was performed using paired t-test, independent t-test, and Mann-Whitney U-Test. Statistical Package for Social Sciences (SPSS) software version 20.0 was used for analysis. The α error of 5% (p-value=0.05) and β error of 20% were taken into consideration. Results: The mean age of the study population was 30.36±4.55 years, with 18 males and 12 females. There was a decrease in RD, RW, PD, and a gain in CAL and RAL in both groups after three months compared to the baseline values. Additionally, there was an increase in WKG, WAG, and a significant change in the thickness of the gingival biotype from thin to thick in both groups at the end of three months. On inter group comparison, the changes in PD (p-value=1.00), RD (p-value=1.00), RW (0.176), CAL (0.664), RAL (1.00), WKG (p-value=0.313) were not statistically significant at the end of three months. WAG was higher in Group II compared to Group I (p-value=0.014*), and the mean root coverage was greater in Group II (15.62%) than in the control group (11.642%) (p-value=0.005) at the end of three months. There was a statistically significant difference (p-value=0.005*) in Group II (15.62%) compared to the control group (11.642%). Conclusion: Amniotic membrane in combination with CAF proves to be a successful option for root coverage in localised recession defects. However, histological evidence and a greater number of future longitudinal studies are necessary to study the efficacy of this approach. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate, in vitro, the efficiency of a novel apparatus to test the adherence and penetration of bacteria on different membranes for guided regeneration. Methodology: To create the 3D device, Computer Aided Design/Computer Aided Manufacturing (CAD/CAM) systems were used. Three types of biomaterials were tested (n = 6): (DT) a collagen membrane; (DS) a polymer membrane; and (LP) a dense polytetrafluoroethylene barrier. The biomaterials were adapted to the apparatuses and challenged with two different monospecies bacterial culture of A. actinomycetemcomitans b and S. mutans. After 2 h, bacterial adherence and penetration were quantified by counting the number of colony-forming units (CFUs). Two specimens from each group were used for image analysis using Confocal Laser Scanning Microscopy. Statistical analysis was performed. Findings: The DS group had a higher adherence of S. mutans compared to A. actinomycetemcomitans b (p = 0.05). There was less adherence of A. actinomycetemcomitans b in the DS group, compared to the LP (p = 0.011) and DT (p < 0.001) groups. Only the membranes allowed penetration, which was blocked by barriers. The DT group allowed a greater penetration of S. mutans to occur compared to A. actinomycetemcomitans b (p = 0.009), which showed a higher penetration into the DS membranes compared to S. mutans (p = 0.016). The penetration of A. actinomycetemcomitans b through DS was higher compared to its penetration through DT and LP (p < 0.01 for both). DT and DS allowed a greater penetration of S. mutans to occur compared to LP, which prevented both bacterial species from penetrating. Conclusion: The apparatus allowed for the settlement and complete sealing of the biomaterials, enabling standardization. [ABSTRACT FROM AUTHOR]

(1) Introduction: Trust is a cornerstone of the patient–physician relationships. Unforeseen complications in the health care system could jeopardize patients' trust in their physicians. (2) Aim: This article presents a quantitative figure regarding foreseeing the necessity of a three-dimensional quantitative visualization of bone structure and concurrently preparing for an ancillary procedure by a dentist to successfully perform the surgery that could minimize unforeseen complications; (3) Materials and method: This retrospective study has been derived based on an analysis of 1134 patients who had received 4800 dental implants from January 2001 to August 2020, out of which 200 cases were randomly selected for this study. Each procedure during implant treatment was categorized as OPG (Orthopantomography) or OPG with CBCT as per all the procedures which included and were coded as follows, 1: Surgery & Restoration, 2: GBR (Guided Bone Regeneration), 3: GTR (Guided Tissue Regeneration), 4: Block Bone Graft, 5: Spreading, 6: Splitting, 7: Internal Sinus, 8: External Sinus, 9: PRF (Platelet Rich Fibrin). Any of the 200 cases in which implant placement could not have been performed for reasons related to a lack of CBCT were selected for this study. The surgery was aborted halfway through without implant placement in these cases due to a lack of bone quantity and/or lack of primary stability. These cases were registered for re-evaluation and statistical analysis; (4) Results: 7% of the cases that used OPG alone led the surgeon to unexpectedly abort in the middle of the surgery without implant placement. All (100%) of the patients who had CBCT during treatment planning were able to receive implants during the surgery. None of the patients left the surgery without receiving implants if CBCT was used (0%); (5) Discussion: Radiographic image quality is defined as the amount of information within the image that allows the radiologist to make a diagnostic decision with a particular level of certainty (Martin et al., 1999) and hence the importance of CBCT. The unexpected 7% of devastating situations for patients who started surgery but did not have implant placement led to [A] aborting the surgery, [B] procedural difficulties requiring an alternative treatment plan, [C] a negative impact on the patient's behavior, and [D] wanting to change doctor due to a lack of trust; (6) Conclusion: This study indicates that in implant dentistry patients' mistrust could be avoided by 7% if CBCT is obtained. It also shows the significance of cone-beam computed tomography as an adjunct to panoramic radiography during the diagnosis and treatment planning phase. The use of panoramic radiography alone can lead to a 7% likelihood of misdiagnosis. A lack of CBCT during treatment planning negatively affects the outcome of surgical procedures. [ABSTRACT FROM AUTHOR]

Introduction: Physical factors like stiffness and surface features are among the characteristics that affect the performance of barrier membranes and determine the results of regenerative processes. A perfect equilibrium between the membrane’s rigidity and mechanical stability guarantees effective periodontal regeneration. The study’s novelty lies in comparing the physical characteristics, namely morphology, tensile strength, wettability, and biological characteristics, namely biocompatibility and enzyme resistance properties, of the Fix-GideTM membrane against the gold standard membrane, Bio-Gide®. Aim: To explore the physical and biological properties of two commercially available barrier membranes in oral tissue regeneration. Materials and Methods: The present in-vitro study compared two commercially available membranes, namely Bio-Gide® and Fix-GideTM. Both membranes are bilayered resorbable membranes, with Bio-Gide composed of porcine dermis Type-I and III collagen and Fix-GideTM of bovine origin. The study was conducted at the Central Leather Research Institute, and the membranes were procured from Sri Ramachandra Institute of Higher Education and Research. Morphological characterisation was done using Scanning Electron Microscopy (SEM). Physical properties were evaluated using a tensile strength test, enzyme resistance test, and wettability measurement. Biocompatibility assessment was also performed. The Statistical Package for Social Sciences (SPSS) software was used to run the Mann-Whitney U test to analyse the statistical data obtained in the enzyme resistance test. Results: Biocompatibility assessment showed no cytotoxic profile of both membranes, portraying their biocompatible nature. Morphological analysis using SEM showed the surface of the Bio-Gide® membrane to be considerably smoother than the Fix-GideTM membrane. Both membranes, however, have fibrous and porous features on their inner surfaces. Tensile strength assessment found that the percentage of elongation was better with Bio-Gide (1.7±0.4 and 4.8±0.4) when compared to Fix-Gide (15.8±0.2 and 2.2±0.2) in both wet and dry states, respectively. The enzyme resistance test evaluated in dry and wet settings showed that the membranes, namely, Bio-Gide® membrane exhibited around 29±2% of degradation, whereas the Fix-GideTM exhibited only 18±2%. These mechanical profiles exhibited that the membranes has appreciable differences, although there wasn’t a statistically significant difference between them (p=0.68). According to wettability studies, Bio-Gide is hydrophilic, but Fix-GideTM is hydrophobic. Conclusion: The observations of the present study showed that Fix-Gide had comparable physio-biological properties to that of the Bio-Gide membrane. This supports the suitability of the use of both membranes for various oral tissue regeneration procedures.

Abstract Background The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. Methods D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn’s test or the Bonferroni test for pairwise comparisons. Results A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p

Di Wang,1,2 Qiqi Li,1,2 Chunsheng Xiao,2 Hao Wang,2 Shujun Dong1 1The First Outpatient Department, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Hao Wang, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Chaoyang District, Changchun, 130022, People’s Republic of China, Tel +86-431-85262110, Email wangh@ciac.ac.cn Shujun Dong, The First Outpatient Department, Hospital of Stomatology, Jilin University, Room 101, Building G5, Phase 3, China Resources Ziyun Mansion, the Intersection of Jinhu Road and Nanhu Middle Street, Nanguan District, Changchun, 130021, People’s Republic of China, Tel +86-431-80621155, Email dsj@jlu.edu.cnAbstract: Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis. Keywords: anti-inflammatory, antibacterial, guided tissue regeneration, nanofibers, hydrogel, films

Introduction: Gingival recession is the exposure of the root surface of the tooth, characterised by the displacement of the gingival margin apically from the Cementoenamel Junction (CEJ). Various techniques have been suggested for treating recession, such as Free Gingival Graft (FGG), Connective tissue grafts, laterally or Coronally Advanced Flaps (CAF), and Guided Tissue Regeneration (GTR)-based procedures. Different membranes have been used for GTR, one of which is the amnion membrane. Aim: To evaluate root coverage using Coronally Advanced Flap (CAF) with and without amniotic membrane in the treatment of localised gingival recession. Materials and Methods: A randomised controlled trial was conducted at Pandit Deendayal Upadhyay Dental College and Hospital, Solapur, Maharashtra, India from March 2017 to February 2018. In this study, 30 teeth were treated, with 15 teeth undergoing CAF with amniotic membrane (Group II-Test Group) and 15 teeth treated with CAF without amniotic membrane (Group I-Control Group). Probing Depth (PD), Clinical Attachment Level (CAL), Relative Attachment Level (RAL), Recession Width (RW), Recession Depth (RD), Width of Keratinised Gingiva (WKG), Width of Attached Gingiva (WAG), and gingival biotype were assessed between baseline and after three months. Statistical analysis was performed using paired t-test, independent t-test, and Mann-Whitney U-Test. Statistical Package for Social Sciences (SPSS) software version 20.0 was used for analysis. The α error of 5% (p-value=0.05) and β error of 20% were taken into consideration. Results: The mean age of the study population was 30.36±4.55 years, with 18 males and 12 females. There was a decrease in RD, RW, PD, and a gain in CAL and RAL in both groups after three months compared to the baseline values. Additionally, there was an increase in WKG, WAG, and a significant change in the thickness of the gingival biotype from thin to thick in both groups at the end of three months. On inter group comparison, the changes in PD (p-value=1.00), RD (p-value=1.00), RW (0.176), CAL (0.664), RAL (1.00), WKG (p-value=0.313) were not statistically significant at the end of three months. WAG was higher in Group II compared to Group I (p-value=0.014*), and the mean root coverage was greater in Group II (15.62%) than in the control group (11.642%) (p-value=0.005) at the end of three months. There was a statistically significant difference (p-value=0.005*) in Group II (15.62%) compared to the control group (11.642%). Conclusion: Amniotic membrane in combination with CAF proves to be a successful option for root coverage in localised recession defects. However, histological evidence and a greater number of future longitudinal studies are necessary to study the efficacy of this approach.

Guided tissue regeneration (GTR) has been widely used in the periodontal treatment of intrabony and furcation defects for nearly four decades. The treatment outcomes have shown effectiveness in reducing pocket depth, improving attachment gain and bone filling in periodontal tissue. Although applying GTR could reconstruct the periodontal tissue, the surgical indications are relatively narrow, and some complications and race ethic problems bring new challenges. Therefore, it is challenging to achieve a consensus concerning the clinical benefits of GTR. With the appearance of stem cell-based regenerative medicine, mesenchymal stem/stromal cells (MSCs) have been considered a promising cell resource for periodontal regeneration. In this review, we highlight preclinical and clinical periodontal regeneration using MSCs derived from distinct origins, including non-odontogenic and odontogenic tissues and induced pluripotent stem cells, and discuss the transplantation procedures, therapeutic mechanisms, and concerns to evaluate the effectiveness of MSCs.

Background. Applying autologous growth factors and diode laser in periodontal therapy enhances fibroblast-mediated new attachment and osteoblastic differentiation. Hence, this study compared and evaluated the effectiveness of concentrated growth factor (CGF) alone and with diode laser application in managing intrabony periodontal defects. Methods. Ten patients with stage III periodontitis were included in this study. All the patients underwent an open flap debridement (OFD) procedure followed by CGF membrane placement in the intrabony defect in site A, whereas, in site B, after OFD, all the patients underwent diode laser irradiation before CGF membrane placement. Plaque and gingival bleeding index (PI & GBI), PPD, and clinical attachment level (CAL) were evaluated at baseline and 3 and 6 months later. Bone fill (BF), BF%, bone crest changes (BCC), and BCC% were assessed radiographically at six months postoperatively. Results. Significant reductions in PI and GBI scores, probing pocket depth (PPD), and CAL gain were observed at both sites 3 and 6 months from baseline. A significant reduction in PPD and CAL gain was noted between sites, which were higher in site B than in site A with a mean difference of 0.70±0.05 mm and 1.30±0.18 mm, 0.90±1.89 mm at 3 and 6 months, respectively. Radiographic measurement showed better BF, BF%, BCC, and BCC% at both sites at six months, which were higher at site B than at site A but statistically insignificant. Conclusion. The combination of CGF and diode laser application has demonstrated successful and promising results in terms of regeneration, improving the clinical and radiographic parameters.

This case report exhibits a heavy smoker female patient with a localized stage III periodontitis who has been under cessation smoking program during the pre-surgical period, followed by a strict maintenance program for the past twelve years, after being treated with guided tissue regeneration techniques and restored with zirconia prosthetic crowns. A 50-year-old, heavy smoker (> 40 cigarettes per day), systemically healthy female patient presented complaining of mobility and pain in the upper right central incisor which was temporarily splinted to the left central incisor using resin composite. After clinical and radiographic examination, significant damage of the attachment apparatus, deep periodontal lesions extending the middle portion of the root, and severe infrabony defect were noted. Following the initial hygienic phase, a guided tissue regeneration surgery using xynograft bone substitute covered by a resorbable collagen membrane was performed. After six months of healing, four zirconia crowns were cemented on the central and lateral incisors based on patient esthetic compliance. During the 12-year follow-up period, neither residual pockets nor gingival recession were observed, and perfect marginal bone stability, and esthetic and functional results were noted. This case shows the predictability of a conservative surgical technique, the guided tissue regeneration, based on appropriate treatment planning and a strict maintenance program, it also demonstrates the importance of at least a 6-month healing period after such surgeries, allowing complete tissue maturation and a re-establishment of the supra osseous gingival tissues in order to locate the prosthetic margins without interfering with the soft tissues integrity.

Introduction: Recent studies have demonstrated a positive role of hyaluronic acid (HA) on periodontal clinical outcomes. This in-vitro study aimed to investigate the impact of four different HAs on interactions between periodontal biofilm and immune cells. Methods: The four HAs included: high-molecular-weight HA (HHA, non-crosslinked), low-molecular-weight HA (LHA), oligomers HA (OHA), and cross-linked high-molecular-weight HA (CHA). Serial experiments were conducted to verify the influence of HAs on: (i) 12-species periodontal biofilm (formation and preexisting); (ii) expression of inflammatory cytokines and HA receptors in monocytic (MONO-MAC-6) cells and periodontal ligament fibroblasts (PDLF) with or without exposure to periodontal biofilms; (iii) generation of reactive oxygen species (ROS) in MONO-MAC-6 cells and PDLF with presence of biofilm and HA. Results: The results indicated that HHA and CHA reduced the bacterial counts in a newly formed (4-h) biofilm and in a pre-existing five-day-old biofilm. Without biofilm challenge, OHA triggered inflammatory reaction by increasing IL-1b and IL-10 levels in MONO-MAC cells and IL-8 in PDLF in a time-dependent manner, whereas CHA suppressed this response by inhibiting the expression of IL-10 in MONO-MAC cells and IL-8 in PDLF. Under biofilm challenge, HA decreased the expression of IL-1b (most decreasing HHA) and increased IL-10 levels in MONOMAC-6 cells in a molecular weight dependent manner (most increasing CHA). The interaction between HA and both cells may occur via ICAM-1 receptor. Biofilm stimulus increased ROS levels in MONO-MAC-6 cells and PDLF, but only HHA slightly suppressed the high generation of ROS induced by biofilm stimulation in both cells. Conclusion: Overall, these results indicate that OHA induces inflammation, while HHA and CHA exhibit anti-biofilm, primarily anti-inflammatory, and antioxidant properties in the periodontal environment. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes. [ABSTRACT FROM AUTHOR]

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4–17) cm in length. After a mean follow-up of 71.84 (61–82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5–28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone. [ABSTRACT FROM AUTHOR]

This study aimed to determine the contribution of titanium prepared platelet-rich fibrin (T-PRF) with open flap debridement (OFD) on clinical, biochemical and radiographic measurements of periodontal regeneration. Twenty periodontitis patients with bilateral intrabony defects and stage III grade A periodontitis were included in the study. A total of 40 defects were randomly selected for OFD alone (control group, n = 20) or combined OFD+ T-PRF (test group, n = 20). Clinical and radiographic parameters (at baseline and nine months after surgery), and growth factor levels in gingival crevicular fluid (at baseline and at two, four, six, and twelve weeks after surgical treatment) were also evaluated. Considering the clinical parameters, alterations in probing pocket depth, gingival marginal level and clinical endpoint in the test regions treated with T-PRF significantly improved (P<0.05). Fibroblast growth factor-2 and platelet-derived growth factor-BB levels between the two groups in the second and fourth weeks were also significantly different (P<0.05). Furthermore, the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio between the groups was significantly different in the second, fourth, sixth, and twelfth weeks (P<0.05). The bone-filling rate was also significantly greater in the test group than in the control group (P <0.001). Compared with OFD alone, combining T-PRF with the procedure was more successful with regards to clinical, radiographic, and biochemical measurements of periodontal regeneration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Proposing the "developmental engineering" strategy in promoting cementum-PDL-alveolar bone complex formation in periodontium regeneration. • Discovering that tuning macrophage immune response can be effective to perform this developmental engineering strategy mediated by PDLCs. • Consideration of applying periodontal development engineering strategy in periodontal multi-tissue regeneration was shown. Periodontal regeneration, specifically the restoration of the cementum-periodontal ligament (PDL)-alveolar bone complex, remains a formidable challenge in the field of regenerative dentistry. In light of periodontal development, harnessing the multi-tissue developmental capabilities of periodontal ligament cells (PDLCs) and reinitiating the periodontal developmental process hold great promise as an effective strategy to foster the regeneration of the periodontal complex. This study aims to delve into the potential effects of the macrophage-mediated immune microenvironment on the "developmental engineering" regeneration strategy and its underlying molecular mechanisms. In this study, we conducted a comprehensive examination of the periodontium developmental process in the rat mandibular first molar using histological staining. Through the induction of diverse immune microenvironments in macrophages, we evaluated their potential effects on periodontal re-development events using a cytokine array. Additionally, we investigated PDLC-mediated periodontal re-development events under these distinct immune microenvironments through transcriptome sequencing and relevant functional assays. Furthermore, the underlying molecular mechanism was also performed. The activation of development-related functions in PDLCs proved challenging due to their declined activity. However, our findings suggest that modulating the macrophage immune response can effectively regulate PDLCs-mediated periodontium development-related events. The M1 type macrophage immune microenvironment was found to promote PDLC activities associated with epithelial-mesenchymal transition, fiber degradation, osteoclastogenesis, and inflammation through the Wnt, IL-17, and TNF signaling pathways. Conversely, the M2 type macrophage immune microenvironment demonstrated superiority in inducing epithelium induction, fibers formation, and mineralization performance of PDLCs by upregulating the TGFβ and PI3K-Akt signaling pathway. The results of this study could provide some favorable theoretical bases for applying periodontal development engineering strategy in resolving the difficulties in periodontal multi-tissue regeneration. [ABSTRACT FROM AUTHOR]

This case report exhibits a heavy smoker female patient with a localized stage III periodontitis who has been under the smoking cessation program during the pre-surgical period, followed by a strict maintenance program for the past twelve years, after being treated with guided tissue regeneration techniques and restored with zirconia prosthetic crowns. A 50-year-old, heavy smoker (> 40 cigarettes per day), systemically healthy female patient presented complaining of mobility and pain in the upper right central incisor, which was temporarily splinted to the left central incisor using resin composite. After clinical and radiographic examination, significant damage of the attachment apparatus, deep periodontal lesions extending the middle portion of the root, and severe infrabony defect were noted. Following the initial hygienic phase, a guided tissue regeneration surgery using xenograft bone substitute covered by a resorbable collagen membrane was performed. After six months of healing, four zirconia crowns were cemented on the central and lateral incisors based on patient esthetic compliance. During the 12-year follow-up period, neither residual pockets nor gingival recession were observed, and perfect marginal bone stability, and esthetic and functional results were noted. This case shows the predictability of a conservative surgical technique, the guided tissue regeneration, based on appropriate treatment planning and a strict maintenance program. It also demonstrates the importance of at least a 6-month healing period after such surgeries, allowing complete tissue maturation and a re-establishment of the supra osseous gingival tissues in order to locate the prosthetic margins without interfering with the soft tissues integrity. [ABSTRACT FROM AUTHOR]

Teeth with attachment loss involving the root apex are severely compromised and have a poor periodontal prognosis. In cases where periodontal regeneration is possible, current guidelines suggest that endodontic treatment is performed first. However, root canal treatment increases the overall treatment time and costs, has risks of endodontic complications, and could predispose teeth to mechanical failure. In this case report, two patients diagnosed with periodontitis stage III/IV grade C, no history of smoking or diabetes, and attachment loss involving the root apex of a tooth, were treated with guided tissue regeneration. These two cases are unique because successful periodontal regeneration was carried out without endodontic treatment, and the vitality of these teeth was maintained longitudinally. This report presents the management that led to this clinical outcome, and important guidelines for case selection are identified. Within the limitations of this study, vital teeth with radiographic bone loss involving the apex may be treated successfully with periodontal regeneration and remain vital at least in the short- to medium-term. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cells (MSCs) isolated from the periodontal ligament (hPDL-MSCs) have a high therapeutic potential, presumably due to their immunomodulatory properties. The interaction between hPDL-MSCs and immune cells is reciprocal and executed by diverse cytokine-triggered paracrine and direct cell-to-cell contact mechanisms. For the first time, this study aimed to directly compare the contribution of various mechanisms on this reciprocal interaction using different in vitro co-culture models at different inflammatory milieus. Methods: Three co-culture models were used: indirect with 0.4 μm-pored insert, and direct with or without insert. After five days of co-culturing mitogen-activated CD4+ T lymphocytes with untreated, interleukin (IL)-1β, or tumor necrosis factor (TNF)-α- treated hPDL-MSCs, the CD4+ T lymphocyte proliferation, viability, and cytokine secretion were investigated. The gene expression of soluble and membrane-bound immunomediators was investigated in the co-cultured hPDL-MSCs. Results: Untreated hPDL-MSCs decreased the CD4+ T lymphocyte proliferation and viability more effectively in the direct co-culture models. The direct co-culture model without inserts showed a strikingly higher CD4+ T lymphocyte cell death rate. Adding IL-1β to the co-culture models resulted in substantial CD4+ T lymphocyte response alterations, whereas adding TNF resulted in only moderate effects. The most changes in CD4+ T lymphocyte parameters upon the addition of IL-1β or TNF-α in a direct co-culture model without insert were qualitatively different from those observed in two other models. Additionally, the co-culture models caused variability in the immunomediator gene expression in untreated and cytokine-triggered hPDL-MSCs. Conclusion: These results suggest that both paracrine and cell-to-cell contact mechanisms contribute to the reciprocal interaction between hPDL-MSCs and CD4+ T lymphocytes. The inflammatory environment affects each of these mechanisms, which depends on the type of cytokines used for the activation of MSCs' immunomodulatory activities. This fact should be considered by comparing the outcomes of the different models. [ABSTRACT FROM AUTHOR]

The frontiers of antibacterial materials in the biomedical field are constantly evolving since infectious diseases are a continuous threat to human health. In this work, waste-wool-derived keratin electrospun nanofibers were blended with copper by an optimized impregnation procedure to fabricate antibacterial membranes with intrinsic biological activity, excellent degradability and good cytocompatibility. The keratin/copper complex electrospun nanofibers were multi-analytically characterized and the main differences in their physical–chemical features were related to the crosslinking effect caused by Cu2+. Indeed, copper ions modified the thermal profiles, improving the thermal stability (evaluated by differential scanning calorimetry and thermogravimetry), and changed the infrared vibrational features (determined by infrared spectroscopy) and the chemical composition (studied by an X-ray energy-dispersive spectroscopy probe and optical emission spectrometry). The copper impregnation process also affected the morphology, leading to partial nanofiber swelling, as evidenced by scanning electron microscopy analyses. Then, the membranes were successfully tested as antibacterial materials against gram-negative bacteria, Escherichia coli. Regarding cytocompatibility, in vitro assays performed with L929 cells showed good levels of cell adhesion and proliferation (XTT assay), and no significant cytotoxic effect, in comparison to bare keratin nanofibers. Given these results, the material described in this work can be suitable for use as antibiotic-free fibers for skin wound dressing or membranes for guided tissue regeneration. [ABSTRACT FROM AUTHOR]

The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell–extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL‐matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross‐linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster‐relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin–focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell–ECM interactions. In vivo experiments confirm that faster‐relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration. [ABSTRACT FROM AUTHOR]

Background: Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. Methods: The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. Results: The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. Conclusions: The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes in transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m6A MeRIP sequencing, RIP‐qPCR, and gene modulation techniques, it is demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated m6A RNA methylation to guide macrophages polarization for tissue regeneration. The biomimic chiral nanofibril hydrogels are fabricated using a self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro and in vivo studies indicated that the L‐nanofibrils exhibit a greater propensity to promote M2‐macrophage polarization than D‐nanofibrils, thereby favoring osteogenesis. Then, m6A‐MeRIP sequencing revealed a unique chirality‐dependent m6A methylation level in macrophages, which was gated by a competitive pair of CCM3‐FAK through enantioselectively integrin recognition. L‐nanofibrils considerably suppressed WTAP‐mediated m6A methylation by promoting Itgα3‐FAK expression and paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced WTAP‐mediated m6A methylation by favoring ItgαV‐CCM3 expression and suppressing mechanotransduction. Furthermore, the gain‐of‐function and loss‐of‐function experiments and RIP‐qPCR demonstrate that the WTAP expression could direct macrophage polarization via manipulating the functional molecule B7‐H3 (CD276). Thus, a mechano‐epigenetic mechanism of chirality‐mediated cell‐fate determination is unveiled, which holds remarkable promise in the realm of assisted regenerative material design. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the repair process in rat calvaria filled with synthetic biphasic bioceramics (Plenum® Osshp-70:30, HA:βTCP) or autogenous bone, covered with a polydioxanone membrane (PDO). A total of 48 rats were divided into two groups (n = 24): particulate autogenous bone + Plenum® Guide (AUTOPT+PG) or Plenum® Osshp + Plenum® Guide (PO+PG). A defect was created in the calvaria, filled with the grafts, and covered with a PDO membrane, and euthanasia took place at 7, 30, and 60 days. Micro-CT showed no statistical difference between the groups, but there was an increase in bone volume (56.26%), the number of trabeculae (2.76 mm), and intersection surface (26.76 mm2) and a decrease in total porosity (43.79%) in the PO+PG group, as well as higher values for the daily mineral apposition rate (7.16 µm/day). Histometric analysis presented material replacement and increased bone formation at 30 days compared to 7 days in both groups. Immunostaining showed a similar pattern between the groups, with an increase in proteins related to bone remodeling and formation. In conclusion, Plenum® Osshp + Plenum® Guide showed similar and sometimes superior results when compared to autogenous bone, making it a competent option as a bone substitute. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze the prognostic factors that influence the outcome of periapical surgery. A systematic search of the literature was carried out using PubMed and Scopus databases between January 2000 and December 2023 with no language limitations. The PICO question of the present systematic review was: What prognostic factors may influence the outcome of periapical surgery? The most relevant randomized controlled clinical trials (RCTs), prospective clinical trials, retrospective studies, and meta-analyses (n = 44) were selected from 134 articles. The reviewed literature evidenced that bone-lesion healing could significantly be improved by the absence of deep periodontal pockets (>4 mm), localization in anterior teeth, the absence of pain and/or preoperative symptoms, a size of bone lesion < 5 mm, the use of ultrasound, the correct placement of retrograde filling material, and the use of different biomimetic membranes for guided tissue regeneration (GTR). Some preoperative and intraoperative factors could significantly improve the prognosis of periapical surgery. However, these results were not conclusive, and further high-quality research is required. [ABSTRACT FROM AUTHOR]

Periodontal regeneration requires the re-attachment of oblique and perpendicular periodontal ligament (PDL) fibres to newly formed cementum and alveolar bone, which has proven elusive with existing approaches. In this study, multiple fibre-guiding biphasic tissue engineered constructs were fabricated by melt electrowriting. The biphasic scaffolds were 95 % porous and consisted of a pore size gradient bone compartment and periodontal compartment made of fibre-guiding channels with micro-architectural features ranging from 100 to 60 µm aimed to direct PDL fibre alignment and attachment. In vitro evaluations over 3 and 7 days demonstrated a marked improvement in collagen fibre orientation (over 60 % fully aligned) for scaffolds with micro-architecture ≤100 µm. The biphasic scaffolds were placed on a dentine slice and implanted ectopically, and this demonstrated that all micro-channels groups facilitated oblique and perpendicular alignment and attachment on the dentine with a mean nuclei angle and mean collagen fibre angle of approximately 60° resembling the native periodontal ligament attachment. A further in vivo testing using a surgically created rodent periodontal model highlighted the 80 µm micro-channel group's effectiveness, showing a significant increase in oblique PDL fibre attachment (72 %) and periodontal regeneration (56 %) when compared to all other groups onto the tooth root compared to control groups. Further to this, immunohistochemistry demonstrated the presence of periostin in the newly formed ligament indicating that functional regeneration occurred These findings suggest that scaffold micro-architectures of 100 µm or below can play a crucial role in directing periodontal tissue regeneration, potentially addressing a critical gap in periodontal therapy. Periodontal regeneration remains a significant clinical challenge. Essential to restoring dental health and function is the proper attachment of the periodontal ligament, which is functionally oriented, to regenerated bone and cementum. Our research presents an innovative biphasic scaffold, utilizing Melt Electrowriting to systematically guide tissue growth. Distinct from existing methods, our scaffold is highly porous, adaptable, and precisely guides periodontal ligament fibre attachment to the opposing tooth root and alveolar bone interfaces, a critical step for achieving periodontal functional regeneration. Our findings not only bridge a significant gap in biomaterial driven tissue guidance but also promise more predictable outcomes for patients, marking a transformative advancement in the field. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The study aims to assess the clinical efficacy of periosteal pedicle graft (PPG) as a barrier membrane in guided tissue regeneration (GTR) for gingival recession, intrabony, and furcation defects. Materials and Methods: Electronic and hand searches were performed to identify randomized controlled/clinical trials investigating GTR using PPG, with 6-month follow-up. Primary outcomes recorded: probing depth (PD), clinical attachment level (CAL), bone fill, recession depth (RD) reduction, percentage of mean root coverage, keratinized tissue width (KTW), and bone defect area (BDA). Results: Thirteen articles were selected; 6 for recession, 2 for furcation, and 5 for intrabony. Meta-analysis was performed whenever possible, results expressed as pooled standardized mean differences (SMDs). I n recession defects, the RD pooled SMD is 0.47 (95% confidence interval (CI) = [-0.50-1.44]), KTW pooled SMD is 1.30 (95% CI = [-0.30-2.91]), favoring PPG over the comparator. In furcation defects, PD pooled SMD is 1.12 (95% CI = [-2.77-0.52]), CAL pooled SMD is 0.71 (95% CI = [-1.09-2.50]), and bone fill pooled SMD is 0.67 (95% CI = [-3.34-4.69]) favoring PPG. In intrabony defects, PD pooled SMD is 0.54 (95% CI = [-2.12-1.04]), CAL pooled SMD is 0.23 (95% CI = [-1.13-0.68]), and BDA pooled SMD is 0.37 (95% CI = [-1.58-2.31]) favoring PPG. The results were not statistically significant. Conclusion: The current evidence indicates that PPG constitutes a valid and reliable alternative to collagen barrier membranes for successful GTR. [ABSTRACT FROM AUTHOR]

The present systematic review was performed to assess the application of orally derived stem cells in periodontal regenerative therapy, and because of this, the following PICO question was proposed: "In patients with periodontitis, can the adjunctive use of orally derived stem cells provide additional clinical and radiographic benefits for periodontal regeneration?". Randomized clinical studies were electronically and manually searched up until December 2023. Quantitative analyses were performed with the aim of evaluating the mean differences (MDs) between the treatment and control groups in terms of clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, gingival recession (GR), and radiographic bone gain (RBG) using random effect models. A total of seven studies were selected for the systematic review. Meta-analyses excluding studies with a high risk of bias highlighted a non-statistically significant result for the use of stem cells when compared to the control groups in terms of CAL gain [MD = 1.05; 95% CI (−0.88, 2.97) p = 0.29] and PPD reduction [MD = 1.32; 95% CI (−0.25, 2.88) p = 0.10]. The same also applied to GR [MD = −0.08; 95% CI (−0.79, 0.63) p = 0.83] and RBG [MD = 0.50; 95% CI (−0.88, 1.88) p = 0.48]. Based on the high heterogeneity, there is not enough evidence to consider the adjunctive application of orally derived mesenchymal stem cells as a preferential approach for periodontal regenerative treatment, as compared to standard procedures. [ABSTRACT FROM AUTHOR]

In cases of severe horizontal atrophy, implant placement requires bone reconstruction procedures. The aim of this randomized controlled trial is to compare the outcomes of bone augmentation with simultaneous implant placement using the shell technique to the outcomes of guided bone regeneration (GBR) in cases of severely horizontal bone atrophy. This study was designed as a monocentric, parallel-group, randomized controlled trial with a six-month follow-up. Among the primary outcomes of this study, peri-implant bone regeneration and peri-implant bone defect closure were selected. Forty-four patients were recruited and equally divided between two groups. In the GRB group, a horizontal regeneration of 2.31 ± 0.23 mm was observed opposed to a horizontal regeneration of 2.36 ± 0.17 mm in the shell group (p = 0.87). A volumetric increase was observed in both groups, with an increase of 0.30 ± 0.12 cm3 in the GBR group and an increase of 0.39 ± 0.09 cm3 in the shell group, highlighting a significant difference between the two groups (p = 0.02). In conclusion, bone augmentation with simultaneous implant placement using the shell technique or guided bone regeneration in horizontal bone atrophy are both predictable therapeutic options. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty-eight female rats were randomly divided into two groups: (O) ovariectomized and (S) placebo groups. After 45 days of osteoporosis induction, two critical-size defects (5 mm diameter) were created on the calvaria. The groups were subdivided according to the following treatment: (C) Clot, MLT, MLT associated with Bio-Oss® (MLTBO), and Bio-Oss® (BO). After 45 days, the defect samples were collected and processed for microtomography, histomorphometry, and biomolecular analysis (Col-I, BMP-2, and OPN). All animals had one femur harvested to confirm the osteoporosis. Microtomography analysis demonstrated a bone mineral density reduction in the O group. Regarding bone healing, the S group presented greater filling of the defects than the O group; however, in the O group, the defects treated with MLT showed higher mineral filling than the other treatments. There was no difference between the treatments performed in the S group (p = 0.05). Otherwise, O-MLT had neoformed bone higher than in the other groups (p = 0.05). The groups that did not receive biomaterial demonstrated lower levels of Col-I secretion; S-MLT and S-MLTBO presented higher levels of OPN, while O-C presented statistically lower results (p < 0.05); O-BO showed greater BMP-2 secretion (p < 0.05). In the presence of ovariectomy-induced osteoporosis, MLT treatment increased the newly formed bone area, regulated the inflammatory response, and increased OPN expression. [ABSTRACT FROM AUTHOR]

Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients. [ABSTRACT FROM AUTHOR]

Background: Decellularized extracellular matrix (dECM) from several tissue sources has been proposed as a promising alternative to conventional scaffolds used in regenerative endodontic procedures (REPs). This systematic review aimed to evaluate the histological outcomes of studies utilizing dECM-derived scaffolds for REPs and to analyse the contributing factors that might influence the nature of regenerated tissues. Methods: The PRISMA 2020 guidelines were used. A search of articles published until April 2024 was conducted in Google Scholar, Scopus, PubMed and Web of Science databases. Additional records were manually searched in major endodontic journals. Original articles including histological results of dECM in REPs and in-vivo studies were included while reviews, in-vitro studies and clinical trials were excluded. The quality assessment of the included studies was analysed using the ARRIVE guidelines. Risk of Bias assessment was done using the (SYRCLE) risk of bias tool. Results: Out of the 387 studies obtained, 17 studies were included for analysis. In most studies, when used as scaffolds with or without exogenous cells, dECM showed the potential to enhance angiogenesis, dentinogenesis and to regenerate pulp-like and dentin-like tissues. However, the included studies showed heterogeneity of decellularization methods, animal models, scaffold source, form and delivery, as well as high risk of bias and average quality of evidence. Discussion: Decellularized ECM-derived scaffolds could offer a potential off-the-shelf scaffold for dentin-pulp regeneration in REPs. However, due to the methodological heterogeneity and the average quality of the studies included in this review, the overall effectiveness of decellularized ECM-derived scaffolds is still unclear. More standardized preclinical research is needed as well as well-constructed clinical trials to prove the efficacy of these scaffolds for clinical translation. Other: The protocol was registered in PROSPERO database #CRD42023433026. This review was funded by the Science, Technology and Innovation Funding Authority (STDF) under grant number (44426). [ABSTRACT FROM AUTHOR]

Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability‐ in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti‐inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro‐assembly under pre‐programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS‐containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS‐containing porous layer delivers dual bio‐signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine. [ABSTRACT FROM AUTHOR]

The relevance of this study is conditioned by the widespread use of stem cells in veterinary medicine, a wide range of studies and ambiguous data on the oncoprotective properties of stem cells of different origins. In this regard, the purpose of this study was to investigate the course of the tumour process in Lewis lung carcinoma and the specific features of the effect of allogeneic mesenchymal stem cells of red bone marrow culture on it. The leading approach to investigating this problem was the method of modelling Lewis lung carcinoma in C57BL6 mice and the use of stem cells. The use of allogeneic mesenchymal stem cells from the bone marrow culture of C57BL6 mice with transplanted epidermoid metastatic carcinoma of the Lewis lung contributed to the activation of the tumour process. Under the influence of allogeneic mesenchymal stem cells of red bone marrow culture from Day 14 to Day 24 of the study, the body weight of mice decreased by 7.0-12.1% (P < 0.05) compared to the control, the diameter of the primary tumour increased by 1.43-1.51 times (P < 0.05), which is conditioned by the activation of primary tumour growth. The number of lymphocytes as producers of vascular growth factor in primary tumour tissue under the influence of allogeneic mesenchymal stem cells of red bone marrow culture significantly increased by 1.47 and 1.52 times on Day 18 of the experiment compared to animals of the control group and placebo (P < 0.05), respectively. This promoted angiogenesis in the primary tumour node and metastasis through the circulatory system. After administration allogeneic mesenchymal cells of red bone marrow culture to mice, a larger volume of lung metastases was recorded, which was 41.52 ± 7.9 mm3 compared to the values in the control and placebo groups, respectively, 17.94 ± 6.59 and 16.43 ± 5.32 mm3. The morphological picture of the histological sections of the primary tumour of Lewis lung carcinoma confirms all the signs of qualitative and quantitative indicators of its progression. The findings obtained are of both theoretical and practical value for clinical veterinary medicine on the use of allogeneic bone marrow mesenchymal stem cells in tumour processes. [ABSTRACT FROM AUTHOR]

A thorough cleaning and shaping of root canals is one of the primary objectives of root canal treatment. For that the clinician needs to be aware of different variations in root canal configurations. The purpose of this article is to report the successful treatment of middle distal canal with type VIII vertucci's root canal configuration. Treatment plan included the non surgical root canal treatment of right mandibular first molar with five canals followed by periodontal management of mesial bony defect. Re-examination at 6 months after the periodontal surgery revealed reduction in PD (from 13 to 5 mm) and with no sign of bleeding on probing. Radiographic follow up showed bone formation in the periodontal intrabony defect. A progressive bony healing appeared radiographically and all signs and symptoms absent after 6 months of thorough root canal treatment with periodontal management of mesial bony defect of right manidibular first molar. [ABSTRACT FROM AUTHOR]