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Periodontal Disease and Periodontal Tissue Regeneration—Second Edition

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 12344

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Dr. Irina-Georgeta Sufaru

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Department of Periodontology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania
Interests: periodontitis etiopathogeny; periodontal medicine; periodontal surgery; periodontal adjunctive treatment
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Prof. Dr. Sorina Mihaela Solomon

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Odontology-Periodontology and Fixed Prosthodontics Department, Faculty of Dental Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
Interests: periodontal risk factors; periodontal non-surgical therapy; periodontal surgical therapy; periodontal adjunctive treatment
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Special Issue Information

Dear Colleagues,

We cordially extend an invitation for you to submit a manuscript for our forthcoming Special Issue on “Periodontal Disease and Periodontal Tissue Regeneration—Second Edition”.

Further clarification is needed regarding the onset and evolutionary mechanisms of periodontal disease to ensure appropriate treatment. It is imperative that there is a clear understanding of the underlying causes and factors contributing to the disease. This understanding will facilitate the development of effective treatment plans tailored to individual patients’ needs, ultimately improving patient outcomes.

Advancing our understanding of periodontal tissue regeneration is imperative to enhance the quality of life for patients affected by periodontal diseases. Innovations in periodontal tissue engineering hold the promise of revolutionizing dental healthcare, emphasizing the urgency of ongoing research.

All review articles, research articles, and techniques on advanced technologies and methods for periodontal diagnosis and the surgical approach for periodontal tissue regeneration are of interest to this Special Issue. Your contribution to this topic would be greatly appreciated and could potentially provide valuable insights into this area of research. We look forward to receiving your submission and are confident that your work will be of great interest to our readers.

Dr. Irina-Georgeta Sufaru
Prof. Dr. Sorina Mihaela Solomon
Guest Editors

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Keywords

periodontal diagnosis
periodontal immunology
periodontal microbiology
periodontal tissue regeneration
tissue engineering

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Related Special Issue

Periodontal Disease and Periodontal Tissue Regeneration in Biomedicines (10 articles)

Published Papers (9 papers)

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Research

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27 pages, 1846 KB

Open AccessArticle

Salivary NETosis-Related and Oxidative Stress Biomarkers Define a Conventional Cigarette Smoking-Associated Inflammatory Phenotype in Periodontitis: A Cross-Sectional Observational Study

by Irina-Georgeta Sufaru, Luminita Lazar, Alexandra Cornelia Teodorescu, Norina Consuela Forna, Doriana Agop-Forna, Ana Petra Lazar, Maria Iacob, Teofana Amarie and Sorina Mihaela Solomon

Biomedicines 2026, 14(6), 1272; https://doi.org/10.3390/biomedicines14061272 - 2 Jun 2026

Viewed by 230

Abstract

Background/Objectives: Cigarette smoking is a major risk factor for periodontitis, but the salivary host-response profile associated with smoking-related periodontal inflammation remains incompletely characterized. This study compared salivary NETosis-related and oxidative-inflammatory biomarkers among current smokers, former smokers, and never-smokers with periodontitis. Methods: This cross-sectional study included 159 systemically healthy adults with periodontitis (53 per group: current smokers, former smokers, never-smokers). Individuals with systemic diseases or concomitant medications that could interfere were excluded. Unstimulated whole saliva was analyzed for NETosis-related biomarkers (MPO-DNA complexes, citrullinated histone H3, neutrophil elastase, cell-free DNA) and oxidative-inflammatory markers (MMP-8, IL-1β, IL-6, TNF-α, 8-OHdG, total antioxidant capacity). Results: Salivary MPO-DNA complexes differed significantly among groups (current smokers 33.52 ± 9.96, former smokers 26.90 ± 8.38, never-smokers 19.20 ± 7.50 ng/mL; p < 0.001, η² = 0.317). The composite NETosis score (η² = 0.702) and oxidative-inflammatory score (η² = 0.718) showed the same graded pattern. Biochemical verification confirmed clear group separation (salivary cotinine: current smokers 312.3 ± 77.0, former smokers 9.7 ± 5.1, never-smokers 3.2 ± 1.4 ng/mL). Smoking exposure was positively correlated with biomarker levels and the severity of periodontal disease. Smoking status remained independently associated with MPO-DNA complexes and the NETosis score after covariate adjustment. Conclusions: Current smoking was associated with an enhanced salivary NETosis-related and oxidative-inflammatory phenotype. Former smokers displayed an intermediate profile. Salivary MPO-DNA complexes and composite biomarker scores warrant further investigation as candidate non-invasive indicators of smoking-associated periodontal inflammatory burden, pending diagnostic performance analyses and prospective validation. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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28 pages, 10888 KB

Open AccessArticle

Diacerein Downregulates Nfkb, Induces ALP Activity and Inhibits Osteoblast Apoptosis in Alveolar Bone of Rats with Periodontitis

by Paulo Sérgio Cerri, Lucas de Andrade Rodrigues, Lays Cristina Gouvea, Gabriella de Oliveira and Estela Sasso-Cerri

Biomedicines 2026, 14(2), 306; https://doi.org/10.3390/biomedicines14020306 - 29 Jan 2026

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Objectives: We evaluated the effect of diacerein, an anti-inflammatory drug, on the activity and survival of alveolar bone osteoblasts in rats with periodontitis. Methods: The rats with periodontitis received diacerein (PDG) or saline solution (PSG) for 7, 15 and 30 days. In gingiva samples, Nfkb1 and Bmp2 gene expressions were evaluated, and maxillae were processed for light and transmission electron microscopy. Results: In PDG, the tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) immunoexpression decreased in parallel with the increase in alkaline phosphatase (ALP) and bone area over time. At 15 and 30 days, Nfkb1 expression decreased in PDG compared to PSG, whereas at 30 days, the Bmp2 expression was greater in PDG than in PSG. Immunofluorescence for IL-10, an anti-inflammatory cytokine, was greater in PDG than in PSG at 15 and 30 days. In PSG, the significant increase in the number of TUNEL-positive osteoblasts was accompanied by the presence of osteoblasts with condensed chromatin nuclei or caspase-3-immunolabelled osteoblasts. In contrast, the number of TUNEL-positive osteoblasts was significantly lower in PDG than in PSG specimens at all time points. Conclusions: Therefore, the diacerein-induced TNF-α and IL-1β inhibitory effect caused Nfkb1 downregulation and, hence, prevented apoptosis in osteoblasts. The increased ALP activity and IL-10 in PDG indicate that diacerein mitigates periodontitis impact on alveolar bone in rat molars. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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22 pages, 2245 KB

Open AccessArticle

Comparative Evaluation of Injectable Platelet-Rich Fibrin with and Without Microneedling in Periodontal Regeneration: A Prospective Split-Mouth Clinical Study

by Iulia Muntean, Alexandra Roi, Lavinia Cosmina Ardelean and Laura-Cristina Rusu

Biomedicines 2026, 14(1), 135; https://doi.org/10.3390/biomedicines14010135 - 9 Jan 2026

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Background/Objectives: Periodontal disease is a prevalent chronic inflammatory condition that often progresses to irreversible tissue destruction. This study aimed to evaluate the clinical efficacy of a combined minimally invasive periodontal therapeutic protocol scaling and root planing (SRP) with injectable platelet-rich fibrin (i-PRF) and microneedling (MN) compared to conventional SRP with i-PRF alone in patients with stage II–III periodontitis. Methods: A prospective split-mouth clinical study was conducted on 54 patients diagnosed according to the 2018 EFP/AAP classification. Each participant received SRP + i-PRF in the upper arch (control) and SRP + i-PRF + MN in the lower arch (test). Periodontal parameters clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) were measured at baseline, 1, 3, and 6 months. Data were analyzed using Friedman and Wilcoxon tests with Bonferroni correction. Results: Both treatment protocols produced significant longitudinal improvements in CAL, BOP, and PI (p < 0.001). The most pronounced BOP reduction occurred within the first month, while CAL improvement was progressive and stabilized after six months. The Combined protocol achieved slightly greater CAL gain at 6 months (mean difference ≈ 0.46 mm; p = 0.0013), indicating a modest yet statistically significant advantage in attachment recovery. Correlation analyses confirmed a coherent healing trajectory characterized by early inflammation resolution, plaque control, and later tissue stabilization. Conclusions: Both i-PRF-based regenerative approaches significantly improved periodontal parameters. The addition of MN enhanced CAL recovery and may favor early vascularization and collagen remodeling. Although the clinical difference was limited, the biological plausibility and sustained improvement suggest that MN could represent a valuable adjunct to non-surgical regenerative periodontal therapy. Longer-term studies are warranted to assess the durability of these effects. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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12 pages, 2606 KB

Open AccessArticle

Characterization and Anti-Inflammatory Effects on Periodontal Ligament Cells of Citrus limon-Derived Exosome-like Nanovesicles Under Different Storage Temperatures

by Yiming Ma, Chenhao Yu, Guojing Liu, Jia Liu and Qingxian Luan

Biomedicines 2026, 14(1), 99; https://doi.org/10.3390/biomedicines14010099 - 3 Jan 2026

Cited by 1 | Viewed by 1011

Abstract

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

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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14 pages, 889 KB

Open AccessArticle

Autogenous Tooth Bone Grafts with Enamel Matrix Derivates in Non-Contained Intrabony Periodontal Defects—A Case Series Study

by Eleonora Solyom, Kristóf Forgó, Kristof Somodi, Daniel Palkovics, Szilard Vancsa, Peter Windisch, Balint Molnar and Reka Fazekas

Biomedicines 2026, 14(1), 56; https://doi.org/10.3390/biomedicines14010056 - 26 Dec 2025

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Abstract

Background: The predictability of regenerative outcomes in non-contained intrabony periodontal defects remains limited. Autogenous tooth bone grafts (ATB) may represent a biologically active and osteoconductive scaffold with minimal residual graft material. This study evaluated the clinical and radiographic outcomes of ATB combined with enamel matrix derivative (EMD) in intrabony defects. Methods: Nine systemically healthy patients (15 defects) were treated with ATB + EMD in a retrospective proof-of-concept design. Clinical parameters—probing pocket depth (PPD), clinical attachment level (CAL), and gingival recession (GR)—were recorded at baseline and 6 months. Radiographic changes in defect depth and width were also assessed. Statistical significance was set at p < 0.05. Results: Mean PPD decreased from 7.73 ± 0.96 mm to 3.87 ± 0.74 mm (p < 0.001), and CAL improved from 9.20 ± 1.47 mm to 5.53 ± 1.36 mm (p < 0.001). GR changes were not significant. Radiographically, mean defect depth and width were reduced from 3.81 ± 1.59 mm and 2.56 ± 0.75 mm to 0.72 ± 1.08 mm and 0.44 ± 0.70 mm, respectively (p < 0.001). Conclusions: The combination of ATB and EMD yielded substantial clinical and radiographic improvements in intrabony periodontal defects. These findings suggest that autogenous tooth bone grafts may serve as a reliable biologically active scaffold for regenerative periodontal surgery. This is the first study evaluating the combination of EMD and ATB. Within the study limitations, ATB + EMD demonstrated promising regenerative potential, warranting future controlled clinical trials. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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13 pages, 598 KB

Open AccessArticle

Comparative Study of Patients with Periodontal and Parkinson’s Disease: Clinical and Salivary Aspects

by Dragoș Nicolae Ciongaru, Silviu Mirel Piţuru, Stana Păunică, Marina Cristina Giurgiu, George Alexandru Denis Popescu and Anca Silvia Dumitriu

Biomedicines 2025, 13(12), 2885; https://doi.org/10.3390/biomedicines13122885 - 26 Nov 2025

Viewed by 669

Abstract

Introduction: This study investigates the severity of periodontal disease in patients with Parkinson’s disease by comparing clinical and salivary aspects. Materials and Methods: A total of 31 patients were included: 15 with periodontal disease (control group) and 16 with periodontal disease and Parkinson’s disease (study group). Demographic data, periodontal parameters (plaque index, tartar index, bleeding index, probing depth, periodontal pocket index) and salivary parameters included viscosity, pH, and buffering capacity were analyzed. Results: Patients with Parkinson’s disease exhibited slightly lower mean values for plaque accumulation, bleeding on probing, and tartar index compared with the control group, though these differences were not statistically significant. In contrast, salivary parameters, particularly buffering capacity, showed statistically significant differences (p < 0.05) between the groups. Conclusions: Parkinson’s disease impacts periodontal health. Early intervention and integrated care strategies may help mitigate oral health deterioration in Parkinson’s patients. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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12 pages, 780 KB

Open AccessArticle

Determination of Osteocalcin Levels in Gingival Crevicular Fluid to Assess the Effectiveness of Laser Therapy in Patients with Orthodontic Treatment

by Timea Dakó, Luminița Lazăr, Petra Șurlin, Dora-Maria Popescu, Anamaria Bud, Alexandru Vlasa, Mădălina Oprica, Sorina Mihaela Solomon and Ana-Petra Lazăr

Biomedicines 2025, 13(11), 2803; https://doi.org/10.3390/biomedicines13112803 - 17 Nov 2025

Viewed by 887

Abstract

Background/Objectives: Orthodontically induced bone remodeling is a complex process, driven by the interaction between osteoblasts, osteoclasts and various biochemical mediators, in response to mechanical forces applied to the teeth. Monitoring this process can be achieved by identifying biomarkers in gingival crevicular fluid (GCF), a dynamic and non-invasive method. Laser therapy, widely used in other medical fields for bio-stimulation and surgery, does not yet benefit from a standardized protocol in orthodontics. The aim of this study was to evaluate the advantages of using laser therapy during orthodontic treatment by analyzing osteocalcin (OC) in gingival crevicular fluid (GCF). Methods: Based on the inclusion and exclusion criteria, we selected 30 patients who presented dentoalveolar disharmony with crowding, who benefited from fixed orthodontic treatment, using edgewise brackets with the same slot size for all subjects. Laser therapy was performed randomly on one hemiarch (HL), right or left, for each patient, randomly chosen at time T0, after activation of the orthodontic appliance. On the other side, the control hemiarch (HC), the same protocol was followed, but without active light. Laser therapy was performed with a dental laser, with a power of 12 watts, setting the periodontology working mode. GCF was collected at baseline, before activation of the orthodontic appliance (time T0) and 14 days after its activation (time T1) from the control hemiarch (HC) and laser hemiarch (HL). Determination of OC levels, as a marker of bone apposition, was performed by the enzyme-linked immunosorbent assay (ELISA) method. To evaluate laser therapy, OC levels were assessed comparatively between HL and HC. Results: Comparing OC values at times T0 and T1 for HL, we obtained a statistically significant difference (p < 0.0001). No statistically significant difference was detected when comparing OC values in HC between T0 and T1 (p = 0.2422). A statistically significant difference was observed between HC and HL at T1 (p < 0.0001). Conclusions: The higher OC levels observed in the hemiarches where laser therapy was applied, compared to the controls, demonstrate its effectiveness as an adjuvant in bone remodeling during orthodontic treatment. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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Review

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15 pages, 452 KB

Open AccessReview

More than Just a Toothache: Inflammatory Mechanisms Linking Periodontal Disease to Cardiovascular Disease and the Protective Impact of Cardiorespiratory Fitness

by Michael F. Mendoza, Michael A. Anzelmo, Nina M. Suan, Chloe S. Cuccia and Carl J. Lavie

Biomedicines 2025, 13(7), 1512; https://doi.org/10.3390/biomedicines13071512 - 20 Jun 2025

Cited by 4 | Viewed by 5201

Abstract

Periodontal disease is a chronic inflammatory condition that extends beyond the oral cavity and is increasingly recognized as a significant contributor to cardiovascular disease, the leading cause of global mortality. Systemic inflammation serves as the key link between the two, with elevated biomarkers such as C-reactive protein and interleukin-6 observed in individuals with PD, driving endothelial dysfunction and atherogenesis. Epidemiological and mechanistic studies consistently demonstrate that PD not only heightens the risk of major adverse cardiovascular events but is also independently associated with increased all-cause and cardiovascular mortality. In parallel, emerging research underscores the protective role of regular physical activity and improved cardiorespiratory fitness, which attenuate systemic inflammation and may reduce the burden of both PD and CVD. This review integrates current evidence on the shared inflammatory mechanisms linking PD and CVD, highlights the systemic impact of poor oral health, and advocates for incorporating exercise-based interventions and oral health assessments into comprehensive cardiovascular risk management. A multidisciplinary approach—bridging cardiology, dentistry, and preventive medicine—may offer a novel strategy to reduce inflammation-driven morbidity and mortality. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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Other

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18 pages, 1185 KB

Open AccessSystematic Review

Oral Diseases and Brain Pathologies: A Systematic Review with Narrative Synthesis of Clinical, Neuroimaging, and Mechanistic Evidence

by Marines Vega Sanchez, Francisco Córdova, Maria Rodríguez Tatés, Luis Chauca Bajaña, Diego Quiguango Farías, María Flores Araque and Byron Velásquez Ron

Biomedicines 2026, 14(4), 768; https://doi.org/10.3390/biomedicines14040768 - 28 Mar 2026

Viewed by 688

Abstract

Background: Oral diseases such as periodontitis, dental infections, and oral dysbiosis have been increasingly associated with systemic conditions. Emerging evidence suggests a potential relationship between oral health and neurological disorders, including brain abscesses, structural brain alterations, and gliomas. However, the strength and mechanisms of these associations remain incompletely understood. Objective: To systematically review clinical, neuroimaging, genetic, and mechanistic evidence linking oral diseases with brain pathologies. Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and EBSCO, with complementary screening of SciELO, Redalyc, and LILACS databases. Studies evaluating associations between oral diseases (periodontitis, dental infections, caries, or oral microbiota alterations) and neurological outcomes were considered. Eligible study designs included observational clinical studies, Mendelian randomization analyses, neuroimaging studies, and experimental investigations. Seventeen studies met the inclusion criteria. Due to the substantial heterogeneity in study designs, outcomes, and effect metrics, quantitative meta-analysis was not feasible. Findings were therefore synthesized using a structured narrative approach following PRISMA guidelines. Results: Clinical studies consistently identified odontogenic infections as a relevant source of brain abscesses, frequently originating from chronic or clinically silent dental foci. Neuroimaging and genetic studies reported associations between poor oral health indicators and structural brain alterations, including reduced cortical thickness and white matter abnormalities. Experimental investigations suggested potential biological mechanisms involving microbial dissemination, systemic inflammation, and immune modulation. Virulence factors from Porphyromonas gingivalis have been shown to induce inflammatory signaling pathways and immune checkpoint activation in glioma cells. Conclusions: The current evidence suggests a possible association between oral diseases and several brain pathologies. Although causality cannot be established, the findings highlight the importance of oral health as a potentially modifiable factor relevant to neurological health. Further longitudinal and mechanistic studies are required to clarify these relationships. Full article

(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration—Second Edition)

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