Research

16 pages, 2997 KiB

Open AccessArticle

High-Glucose Media Reduced the Viability and Induced Differential Pro-Inflammatory Cytokines in Human Periodontal Ligament Fibroblasts

by Alaa Aldoss, Rhodanne Lambarte and Fahd Alsalleeh

Biomolecules 2023, 13(4), 690; https://doi.org/10.3390/biom13040690 - 19 Apr 2023

Viewed by 1673

Abstract

Hyperglycemic condition in diabetic patients tends to exacerbate periodontitis severity. Thus, the influence of hyperglycemia on the biological and inflammatory response of periodontal ligament fibroblasts (PDLFs) needs to be elucidated. In this study, PDLFs were seeded in media containing glucose concentrations (5.5, 25, [...] Read more.

Hyperglycemic condition in diabetic patients tends to exacerbate periodontitis severity. Thus, the influence of hyperglycemia on the biological and inflammatory response of periodontal ligament fibroblasts (PDLFs) needs to be elucidated. In this study, PDLFs were seeded in media containing glucose concentrations (5.5, 25, or 50 mM) and stimulated with 1 µg/mL of lipopolysaccharide (LPS). PDLFs’ viability, cytotoxicity, and the migration ability were determined. The mRNA expression of Interleukin (IL)-6, IL-10, and IL-23 (p19/p40), and Toll-like receptor (TLR)-4 were analyzed; at 6 and 24 h, protein expression of IL-6 and IL-10 was also determined. PDLFs grown in 50 mM glucose medium showed lower viability. The 5.5 mM glucose led to the highest percentage of wound closure compared to 25 mM and 50 mM glucose with/without LPS. Additionally, 50 mM glucose with LPS exhibited the least migration ability among all groups. The expression of IL-6 was amplified significantly in LPS-stimulated cells in 50 mM glucose medium. IL-10 was constitutively expressed in different glucose concentrations, and LPS stimulation decreased it. IL-23 p40 was up-regulated after LPS stimulation in 50 mM glucose concentration. TLR-4 was highly expressed after LPS stimulation in all glucose concentrations. Hyperglycemic conditions limit PDLF proliferation and migration, and enhance the expression of certain pro-inflammatory cytokines to induce periodontitis. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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11 pages, 897 KiB

Open AccessFeature PaperArticle

Periodontal Regenerative Therapy Using rhFGF-2 and Deproteinized Bovine Bone Mineral versus rhFGF-2 Alone: 4-Year Extended Follow-Up of a Randomized Controlled Trial

by Fumi Seshima, Takahiro Bizenjima, Hideto Aoki, Kentaro Imamura, Daichi Kita, Daisuke Irokawa, Daisuke Matsugami, Yurie Kitamura, Keiko Yamashita, Hiroki Sugito, Sachiyo Tomita and Atsushi Saito

Biomolecules 2022, 12(11), 1682; https://doi.org/10.3390/biom12111682 - 12 Nov 2022

Cited by 7 | Viewed by 2171

Abstract

The aim of this study was to evaluate longitudinal outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus deproteinized bovine bone mineral (DBBM) therapy in comparison with rhFGF-2 alone for treating periodontal intrabony defects. This study describes 4-year follow-up outcomes of the original [...] Read more.

The aim of this study was to evaluate longitudinal outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus deproteinized bovine bone mineral (DBBM) therapy in comparison with rhFGF-2 alone for treating periodontal intrabony defects. This study describes 4-year follow-up outcomes of the original randomized controlled trial. Intrabony defects in periodontitis patients were treated with rhFGF-2 (control) or rhFGF-2 plus DBBM (test). Clinical, radiographic, and patient-reported outcome (PRO) measures were used to evaluate the outcomes. Thirty-two sites were able to be followed up. At 4 years postoperatively, clinical attachment level (CAL) gains in the test and control groups were 3.5 ± 1.4 mm and 2.7 ± 1.4 mm, respectively, showing significant improvement from preoperative values but no difference between groups. Both groups showed an increase in radiographic bone fill (RBF) over time. At 4 years, the mean value for RBF in the test group (62%) was significantly greater than that in the control group (42%). In 1–2-wall defects, the test treatment yielded significantly greater RBF than the control treatment. No significant difference in PRO scores was noted between the groups. Although no significant difference in CAL gain was found between the groups at the 4-year follow-up, the combination treatment significantly enhanced RBF. Favorable clinical, radiographic outcomes, and PRO in both groups can be maintained for at least 4 years. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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13 pages, 2775 KiB

Open AccessArticle

Investigating the Effects of Dehydrated Human Amnion-Chorion Membrane on Periodontal Healing

by Kentaro Imamura, Yusuke Hamada, Wataru Yoshida, Tasuku Murakami, Saki Nakane-Koyachi, Kouki Yoshikawa and Atsushi Saito

Biomolecules 2022, 12(6), 857; https://doi.org/10.3390/biom12060857 - 20 Jun 2022

Cited by 4 | Viewed by 1979

Abstract

Each growth factor (GF) has different effects and targets, and plays a critical role in periodontal healing. Dehydrated human amnion-chorion membrane (dHACM) contains various GFs and has been used to enhance wound healing. The purpose of this study was to evaluate the effects [...] Read more.

Each growth factor (GF) has different effects and targets, and plays a critical role in periodontal healing. Dehydrated human amnion-chorion membrane (dHACM) contains various GFs and has been used to enhance wound healing. The purpose of this study was to evaluate the effects of dHACM on periodontal healing, using in vitro and in vivo experimental approaches. Standardized periodontal defects were created in rats. The defects were randomly divided into three groups: Unfilled, filled with hydroxypropyl cellulose (HPC), and dHACM+HPC. At 2 and 4 weeks postoperatively, periodontal healing was analyzed by microcomputed tomography (micro-CT), and histological and immunohistochemical analyses. In vitro, periodontal ligament-derived cells (PDLCs) isolated from rat incisors were incubated with dHACM extract. Cell proliferation and migration were evaluated by WST-1 and wound healing assay. In vivo, micro-CT examination at 2 weeks revealed enhanced formation of new bone in the dHACM+HPC group. At 4 weeks, the proportions of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (α-SMA)-positive blood vessels in the dHACM+HPC group were significantly greater than those in the Unfilled group. In vitro, dHACM extracts at 100 µg/mL significantly increased cell proliferation and migration compared with control. These findings suggest that GFs contained in dHACM promote proliferation and migration of PDLCs and angiogenesis, which lead to enhanced periodontal healing. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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13 pages, 2933 KiB

Open AccessArticle

Effects of Electric-Toothbrush Vibrations on the Expression of Collagen and Non-Collagen Proteins through the Focal Adhesion Kinase Signaling Pathway in Gingival Fibroblasts

by Kumiko Nakai, Hideki Tanaka, Kyoko Fukuzawa, Jyunya Nakajima, Manami Ozaki, Nobue Kato and Takayuki Kawato

Biomolecules 2022, 12(6), 771; https://doi.org/10.3390/biom12060771 - 01 Jun 2022

Cited by 1 | Viewed by 2343

Abstract

Electric-toothbrush vibrations, which remove plaque, are transmitted to the gingival connective tissue via epithelial cells. Physical energy affects cell function; however, the effects of electric-toothbrush vibrations on gingival extracellular matrix (ECM) protein expression remain unknown. We aimed to examine the effects of these [...] Read more.

Electric-toothbrush vibrations, which remove plaque, are transmitted to the gingival connective tissue via epithelial cells. Physical energy affects cell function; however, the effects of electric-toothbrush vibrations on gingival extracellular matrix (ECM) protein expression remain unknown. We aimed to examine the effects of these vibrations on the expression of ECM proteins—type I collagen (col I), type III collagen (col III), elastin, and fibronectin (FN)—using human gingival fibroblasts (HGnFs). HGnFs were seeded for 5 days in a six-well plate with a hydrophilic surface, exposed to electric-toothbrush vibrations, and cultured for 7 days. Subsequently, the mRNA and protein levels of col I, col III, elastin, and FN were examined. To investigate the role of focal adhesion kinase (FAK) signaling on ECM protein expression in vibration-stimulated cells, the cells were treated with siRNA against protein tyrosine kinase (PTK). Electric-toothbrush vibrations increased col I, col III, elastin, and FN expression; promoted collagen and non-collagen protein production; and enhanced FAK phosphorylation in HGnFs. Moreover, PTK2 siRNA completely blocked the effects of these vibrations on the expression of col I, col III and elastin mRNA. The results suggest that electric-toothbrush vibrations increase collagen, elastin, and FN production through the FAK-signaling pathway in fibroblasts. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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11 pages, 586 KiB

Open AccessArticle

Effect of Locally Delivered Minocycline on the Profile of Subgingival Bacterial Genera in Patients with Periodontitis: A Prospective Pilot Study

by Toshiya Morozumi, Yohei Nakayama, Satoshi Shirakawa, Kentaro Imamura, Kaname Nohno, Takatoshi Nagano, Haruna Miyazawa, Takahiro Hokari, Ryo Takuma, Shuntaro Sugihara, Kazuhiro Gomi, Atsushi Saito, Yorimasa Ogata and Motohiro Komaki

Biomolecules 2022, 12(5), 719; https://doi.org/10.3390/biom12050719 - 18 May 2022

Cited by 2 | Viewed by 2388

Abstract

This prospective pilot study aimed to evaluate the effect of minocycline-HCl ointment (MO), locally delivered as an adjunct to scaling and root planing (SRP), on subgingival microflora. A total of 59 periodontitis patients received SRP as an initial periodontal therapy. In the selected [...] Read more.

This prospective pilot study aimed to evaluate the effect of minocycline-HCl ointment (MO), locally delivered as an adjunct to scaling and root planing (SRP), on subgingival microflora. A total of 59 periodontitis patients received SRP as an initial periodontal therapy. In the selected periodontal pockets with probing depths (PD) of 6–9 mm, the sites that exhibited a positive reaction following a bacterial test using an immunochromatographic device were subsequently treated with MO (SRP + MO group, n = 25). No additional treatment was performed at sites showing a negative reaction (SRP group, n = 34). In addition to subgingival plaque sampling, measurement of clinical parameters including PD, clinical attachment level (CAL), bleeding on probing (BOP), plaque index and gingival index (GI) were performed at baseline and 4 weeks after the initial periodontal therapy. The subgingival microflora were assessed by terminal restriction fragment-length polymorphism analysis. Relative to baseline values, the mean scores for PD-, CAL-, BOP-, and GI-sampled sites were significantly decreased post treatment in both groups (p < 0.01). The intra-comparisons showed a significant decrease in the counts of the genera Eubacterium, Parvimonas, Filifactor, Veillonella, Fusobacterium, Porphyromonas, Prevotella, and unknown species in the SRP + MO group (p < 0.05). Inter-comparisons indicated a significant decrease in the genera Veillonella in the SRP + MO group (p = 0.01). Combination therapy of SRP and local MO induced a change in the subgingival microbial community: particularly, the number of Veillonella spp. was markedly reduced. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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11 pages, 1216 KiB

Open AccessArticle

Periodontal Inflamed Surface Area Mediates the Link between Homocysteine and Blood Pressure

by João Botelho, Vanessa Machado, Yago Leira, Luís Proença and José João Mendes

Biomolecules 2021, 11(6), 875; https://doi.org/10.3390/biom11060875 - 12 Jun 2021

Cited by 5 | Viewed by 2772

Abstract

Here, we assess the association between homocysteine (Hcy) serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES). Using the 2001–2002 and 2003–2004 NHANES databases, participants with a periodontal examination, medical self-reported data, blood [...] Read more.

Here, we assess the association between homocysteine (Hcy) serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES). Using the 2001–2002 and 2003–2004 NHANES databases, participants with a periodontal examination, medical self-reported data, blood pressure (BP) and blood samples to determine complete blood count, C-reactive protein (CRP) and Hcy levels. We then calculated the periodontal inflamed surface area (PISA) and the periodontal epithelial surface area (PESA). Multivariable regression analysis explored the association between Hcy, periodontal measures and BP. Mediation analysis was performed to understand the effect of PISA and PESA in the link between Hcy and BP. 4021 participants fulfilled the inclusion criteria. Hcy levels showed significant correlations with systolic BP, diastolic BP, PISA, PESA and age. PESA showed to be significantly associated with Hcy both for the crude and adjusted models (p < 0.01), but not PISA (p > 0.05). In the association of Hcy with systolic BP, PISA significantly mediated 17.4% and PESA 0.9%. In the association of Hcy with diastolic BP, PISA significantly mediated 16.3% and PESA 47.2%. In conclusion, Hcy and periodontitis are associated. Further, both PISA and PESA significantly mediated the association of Hcy with systolic BP and diastolic BP. Future studies shall deepen the mechanisms by which Hcy levels increase in a clinical situation of periodontitis. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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18 pages, 5021 KiB

Open AccessArticle

Healing of Experimental Periodontal Defects Following Treatment with Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral

by Tasuku Murakami, Daisuke Matsugami, Wataru Yoshida, Kentaro Imamura, Takahiro Bizenjima, Fumi Seshima and Atsushi Saito

Biomolecules 2021, 11(6), 805; https://doi.org/10.3390/biom11060805 - 29 May 2021

Cited by 6 | Viewed by 2612

Abstract

The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + [...] Read more.

The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + DBBM, or left unfilled. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing. In vitro cell viability/proliferation on DBBM with/without FGF-2 was assessed by WST-1. Cell behavior was analyzed using scanning electron and confocal laser scanning microscopy. Osteogenic differentiation was evaluated by staining with alkaline phosphatase and alizarin red. Bone volume fraction was significantly greater in FGF-2 and FGF-2 + DBBM groups than in other groups at 2 and 4 weeks postoperatively. In histological assessment, newly formed bone in FGF-2 and FGF-2 + DBBM groups appeared to be greater than other groups. Significantly greater levels of proliferating cell nuclear antigen-, vascular endothelial growth factor-, and osterix-positive cells were observed in FGF-2 and FGF-2 + DBBM groups compared to Unfilled group. In vitro, addition of FGF-2 to DBBM promoted cell viability/proliferation, attachment/spreading, and osteogenic differentiation. The combination therapy using FGF-2 and DBBM was similarly effective as FGF-2 alone in the healing of experimental periodontal defects. In certain bone defect configurations, the combined use of FGF-2 and DBBM may enhance healing via promotion of cell proliferation, angiogenesis, and osteogenic differentiation. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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Review

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23 pages, 849 KiB

Open AccessReview

Obesity, Bone Loss, and Periodontitis: The Interlink

by Pengfei Zhao, Aimin Xu and Wai Keung Leung

Biomolecules 2022, 12(7), 865; https://doi.org/10.3390/biom12070865 - 22 Jun 2022

Cited by 21 | Viewed by 4851

Abstract

Obesity and periodontitis are both common health concerns that have given rise to considerable economic and societal burden worldwide. There are established negative relationships between bone metabolism and obesity, obesity and diabetes mellitus (DM), and DM and periodontitis, to name a few, with [...] Read more.

Obesity and periodontitis are both common health concerns that have given rise to considerable economic and societal burden worldwide. There are established negative relationships between bone metabolism and obesity, obesity and diabetes mellitus (DM), and DM and periodontitis, to name a few, with osteoporosis being considered a long-term complication of obesity. In the oral cavity, bone metabolic disorders primarily display as increased risks for periodontitis and alveolar bone loss. Obesity-driven alveolar bone loss and mandibular osteoporosis have been observed in animal models without inoculation of periodontopathogens. Clinical reports have also indicated a possible association between obesity and periodontitis. This review systematically summarizes the clinical periodontium changes, including alveolar bone loss in obese individuals. Relevant laboratory-based reports focusing on biological interlinks in obesity-associated bone remodeling via processes like hyperinflammation, immune dysregulation, and microbial dysbiosis, were reviewed. We also discuss the potential mechanism underlying obesity-enhanced alveolar bone loss from both the systemic and periodontal perspectives, focusing on delineating the practical considerations for managing periodontal disease in obese patients. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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Other

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20 pages, 956 KiB

Open AccessSystematic Review

Are Inflamed Periodontal Tissues Endogenous Source of Advanced Glycation End-Products (AGEs) in Individuals with and without Diabetes Mellitus? A Systematic Review

by Aditi Chopra, Thilini N. Jayasinghe and Joerg Eberhard

Biomolecules 2022, 12(5), 642; https://doi.org/10.3390/biom12050642 - 27 Apr 2022

Cited by 12 | Viewed by 2948

Abstract

Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs are associated with insulin resistance and poor glycemic control. Recently, inflamed periodontal tissues and certain oral bacteria were observed to [...] Read more.

Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs are associated with insulin resistance and poor glycemic control. Recently, inflamed periodontal tissues and certain oral bacteria were observed to increase the local and systemic AGE levels in both normoglycemic and hyperglycemic individuals. Although hyperglycemia induced AGE and its effect on the periodontal tissues is known, periodontitis as an endogenous source of AGE formation is not well explored. Hence, this systematic review is aimed to explore, for the first time, whether inflamed periodontal tissues and periodontal pathogens have the capacity to modulate AGE levels in individuals with or without T2DM and how this affects the glycemic load. Six electronic databases were searched using the following keywords: (Periodontitis OR Periodontal disease OR Periodontal Inflammation) AND (Diabetes mellitus OR Hyperglycemia OR Insulin resistance) AND Advanced glycation end products. The results yielded 1140 articles, of which 13 articles were included for the review. The results showed that the mean AGE levels in gingival crevicular fluid was higher in individuals with diabetes mellitus and periodontitis (521.9 pg/mL) compared to healthy individuals with periodontitis (234.84 pg/mL). The serum AGE levels in normoglycemic subjects having periodontitis was higher compared to those without periodontitis (15.91 ng/mL vs. 6.60 ng/mL). Tannerella forsythia, a common gram-negative anaerobe periodontal pathogen in the oral biofilm, was observed to produce methylglyoxal (precursor of AGE) in the gingival tissues. Increased AGE deposition and activate of AGE receptors was noted in the presence of periodontitis in both normoglycemic and hyperglycemic individuals. Hence, it can be concluded that periodontitis can modulate the local and systemic levels of AGE levels even in absence of hyperglycemia. This explains the bidirectional relationship between periodontitis and development of prediabetes, incident diabetes, poor glycemic control, and insulin resistance. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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14 pages, 1053 KiB

Open AccessSystematic Review

The Expression and Regulatory Roles of Long Non-Coding RNAs in Periodontal Ligament Cells: A Systematic Review

by Yifan Lin, Zhongyuan Tang, Lijian Jin and Yanqi Yang

Biomolecules 2022, 12(2), 304; https://doi.org/10.3390/biom12020304 - 12 Feb 2022

Cited by 3 | Viewed by 3153

Abstract

Periodontal ligament (PDL) cells play a pivotal role in periodontal and bone homeostasis and have promising potential for regenerative medicine and tissue engineering. There is compelling evidence that long non-coding RNAs (lncRNAs) are differentially expressed in PDL cells compared to other cell types [...] Read more.

Periodontal ligament (PDL) cells play a pivotal role in periodontal and bone homeostasis and have promising potential for regenerative medicine and tissue engineering. There is compelling evidence that long non-coding RNAs (lncRNAs) are differentially expressed in PDL cells compared to other cell types and that these lncRNAs are involved in a variety of biological processes. This study systematically reviews the current evidence regarding the expression and regulatory functions of lncRNAs in PDL cells during various biological processes. A systematic search was conducted on PubMed, the Web of Science, Embase, and Google Scholar to include articles published up to 1 July 2021. Original research articles that investigated the expression or regulation of lncRNAs in PDL cells were selected and evaluated for a systematic review. Fifty studies were ultimately included, based on our eligibility criteria. Thirteen of these studies broadly explored the expression profiles of lncRNAs in PDL cells using microarray or RNA sequencing. Nineteen studies investigated the mechanisms by which lncRNAs regulate osteogenic differentiation in PDL cells. The remaining 18 studies investigated the mechanism by which lncRNAs regulate the responses of PDL cells to various stimuli, namely, lipopolysaccharide-induced inflammation, tumor necrosis factor alpha-induced inflammation, mechanical stress, oxidative stress, or hypoxia. We systematically reviewed studies on the expression and regulatory roles of lncRNAs in diverse biological processes in PDL cells, including osteogenic differentiation and cellular responses to inflammation, mechanical stress, and other stimuli. These results provide new insights that may guide the development of lncRNA-based therapeutics for periodontal and bone regeneration. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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12 pages, 2087 KiB

Open AccessStudy Protocol

Biomolecules in Dental Applications: Randomized, Controlled Clinical Trial Evaluating the Influence of Hyaluronic Acid Adjunctive Therapy on Clinical Parameters of Moderate Periodontitis

by Iwona Olszewska-Czyz, Kristina Kralik and Jelena Prpic

Biomolecules 2021, 11(10), 1491; https://doi.org/10.3390/biom11101491 - 09 Oct 2021

Cited by 8 | Viewed by 2630

Abstract

The biological activity of hyaluronic acid (HA) has been well-researched during the past decades; however, there are few randomized, controlled trials of its clinical effects in periodontal therapy. The purpose of this study was to evaluate the effect of hyaluronic acid on the [...] Read more.

The biological activity of hyaluronic acid (HA) has been well-researched during the past decades; however, there are few randomized, controlled trials of its clinical effects in periodontal therapy. The purpose of this study was to evaluate the effect of hyaluronic acid on the principal parameters of periodontal healing. A specific, commercially available formulation designed and registered for professional dental application, composed of 16 mg/mL of cross-linked and 2 mg/mL of non-cross-linked HA, was used as an adjunctive to non-surgical periodontal therapy, and clinical parameters were evaluated after 3 months. The addition of HA to periodontal therapy demonstrated more favorable clinical results regarding reduction in inflammation, measured by bleeding on probing (−6% compared to the control group) and gain in periodontal attachment (1 mm more than control group), while it had no effect on probing depth reduction. No side effects were reported. Our study demonstrated that HA is a safe and easy-to-use biological agent; due to its wide array of properties, it may significantly improve the results of periodontal therapy. However, more long-term studies are needed to investigate whether these favorable effects remain over time. Full article

(This article belongs to the Special Issue Advances in Basic and Clinical Periodontal Research)

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