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Biomedicines
Special Issues
Molecular Mechanisms and Therapeutic Approaches for Oral Disorders
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Molecular Mechanisms and Therapeutic Approaches for Oral Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 5558

Special Issue Editors

Dr. Vincenzo Ronsivalle

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Guest Editor
Department of Biomedical and Surgical and Biomedical Sciences, Catania University, 95123 Catania, Italy
Interests: oral pathology; oral medicine; periodontology; oral surgery; oral diseases; dental medicine; oral and maxillofacial pathology; orthodontics; digital dentistry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marco Cicciu

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Guest Editor
Department of Biomedical and Surgical and Biomedical Sciences, Catania University, 95123 Catania, Italy
Interests: oral medicine; oral cancer; oral health; periodontology; periodontal regeneration
Special Issues, Collections and Topics in MDPI journals
Dr. Simona Santonocito

E-Mail Website
Guest Editor
Department of Biomedical and Surgical and Biomedical Sciences, Catania University, 95123 Catania, Italy
Interests: oral pathology; oral medicine; periodontology; oral surgery; oral diseases; dental medicine; oral and maxillofacial pathology; orthodontics

Special Issue Information

Dear Colleagues,

Oral disorders encompass multiple pathologies, with different etiologies and pathogeneses, capable of greatly reducing the quality of life of affected individuals. The oral cavity, due to its special anatomical and functional characteristics, represents a site where conventional buccal drug delivery modalities, such as oral gels, tablets, and lozenges, fail to provide proper and adequate local bioavailability of active agents, as incidental swallowing, short retention times, and variations in saliva production limit their potential in treating various oral conditions. In this context, the development of new oral treatment approaches has become very important.

We are delighted to invite you to contribute to this Special Issue, which aims to assess the current knowledge and explore future perspectives on the molecular mechanisms underlying oral diseases. Understanding these mechanisms is crucial as it can pave the way for the development of more effective treatment strategies. For this Special Issue, we welcome both original research articles and comprehensive reviews.

We look forward to receiving your contributions.

Dr. Simona Santonocito
Prof. Dr. Marco Cicciu
Dr. Vincenzo Ronsivalle
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oral diseases
  • drugs
  • local drug delivery
  • periodontitis
  • causal periodontal therapy
  • oral potential malignant disorders
  • oral cancer
  • oral medicine

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Published Papers (6 papers)

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Research

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13 pages, 463 KiB  
Article
The Association Between Severity of Constipation and Oral Frailty Index-8 in the JUSTICE-TOKYO Study: A Cross-Sectional Study
by Tsutomu Takeda, Daisuke Asaoka, Hiroyuki Kiko, Takuya Kanazawa, Osamu Nomura, Shotaro Oki, Mariko Hojo, Koji Sugano, Kei Matsuno, Hiroyuki Inoshita, Yuji Nishizaki, Naotake Yanagisawa, Mitsuyo Shinohara, Akihito Nagahara and Katsumi Miyauchi
Biomedicines 2025, 13(4), 813; https://doi.org/10.3390/biomedicines13040813 - 28 Mar 2025
Viewed by 434
Abstract
Background/Objectives: Reports on oral frailty as a risk factor for chronic constipation are scarce. In this study, we examined the relationship between Oral Frailty Index-8 (OFI-8) and constipation severity. Methods: This cross-sectional analysis involved patients aged ≥65 years (outpatients between November [...] Read more.
Background/Objectives: Reports on oral frailty as a risk factor for chronic constipation are scarce. In this study, we examined the relationship between Oral Frailty Index-8 (OFI-8) and constipation severity. Methods: This cross-sectional analysis involved patients aged ≥65 years (outpatients between November 2020 and November 2021). Patient background (age, sex, body mass index, medical history, lifestyle history, and oral medications), a constipation severity questionnaire (Constipation Scoring System [CSS]), grip strength, walking speed, skeletal muscle mass index (dual-energy X-ray absorptiometry), a frailty questionnaire, an oral frailty questionnaire (OFI-8), an abdominal symptoms quality of life (QOL) questionnaire (Izumo scale), a swallowing evaluation questionnaire (10-item Eating Assessment Tool [EAT-10]), a chronic obstructive pulmonary disease (COPD) evaluation questionnaire (COPD assessment test [CAT]), a simplified QOL evaluation (EuroQol-five dimensions [EQ-5D]), the Dietary Variety Score, a nutritional evaluation (CONtrolling NUTritional Status [CONUT] score), and the 15-item Geriatric Depression Scale (GDS-15) were analyzed. Risk factors for constipation severity (CSS) were examined using multivariate analysis. Patients with advanced gastrointestinal cancer, inflammatory bowel disease, and active gastroduodenal ulcer were excluded. Results: In total, 1029 patients (male/female: 450/579; mean age: 78.3 ± 6.1 years; mean body mass index: 22.9 ± 3) were included. Multivariate analysis demonstrated a significant association between CSS and OFI-8 (β = 0.065), EAT-10 (β = 0.061), sarcopenia (β = 0.050), laxative (β = 0.126), constipation-related QOL score (β = 0.625), diarrhea-related QOL score (β = −0.064), and CAT (β = 0.061). Conclusions: Comprehensive risk factors associated with CSS included a high oral frailty score, impaired swallowing (EAT-10), sarcopenia, laxative use, a high constipation QOL score, a low diarrhea QOL score, and COPD assessment through CAT. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)
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12 pages, 1179 KiB  
Article
Fatty Acid Binding Protein 4 Could Be a Linking Biomarker Between Periodontitis and Systemic Diseases
by Jiwon Song, Soo-Min Ok, Eun-Young Kwon, Hyun-Joo Kim, Ju-Youn Lee and Ji-Young Joo
Biomedicines 2025, 13(2), 402; https://doi.org/10.3390/biomedicines13020402 - 7 Feb 2025
Viewed by 620
Abstract
Background/Objectives: This study aims to investigate the relationship between serum fatty acid-binding protein 4 (FABP4) levels and the severity of periodontitis in systemically healthy individuals. Additionally, the study examines whether non-surgical periodontal treatment can reduce FABP4 levels, establishing its potential as a [...] Read more.
Background/Objectives: This study aims to investigate the relationship between serum fatty acid-binding protein 4 (FABP4) levels and the severity of periodontitis in systemically healthy individuals. Additionally, the study examines whether non-surgical periodontal treatment can reduce FABP4 levels, establishing its potential as a biomarker linking periodontitis to systemic diseases. Methods: A total of 89 participants with stage I, II, or III periodontitis were recruited, excluding individuals with systemic diseases. Clinical parameters such as clinical attachment level (CAL), probing depth (PD), and gingival index (GI) were recorded. Serum FABP4 levels and Porphyromonas gingivalis (P. gingivalis) antibody titers were measured before and after periodontal treatment using ELISA kits. Statistical analysis included t-tests, correlation analysis, and multiple linear regression to assess changes in FABP4 levels and their association with clinical parameters. Results: FABP4 and P. gingivalis antibody titers significantly increased with the severity of periodontitis (p < 0.001). After non-surgical periodontal treatment, FABP4 levels significantly decreased across all stages of periodontitis. Moderate positive correlations were observed between FABP4 and CAL, PD, GI, and P. gingivalis antibody titers (p < 0.05). Multiple linear regression showed that FABP4 levels increased significantly with the progression of periodontitis, independent of age and sex. Conclusions: The study indicates that FABP4 is a potential biomarker for linking periodontitis to systemic conditions such as cardiovascular diseases and diabetes. Non-surgical periodontal treatment reduced FABP4 levels, potentially contributing to the improvement of systemic conditions associated with elevated FABP4. Further research should explore the role of FABP4 in patients with periodontitis and systemic diseases to strengthen its clinical relevance. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)
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16 pages, 2692 KiB  
Article
Hyaluronic Acid Combined with Ozone in Dental Practice
by Alessio Rosa, Alberto Maria Pujia and Claudio Arcuri
Biomedicines 2024, 12(11), 2522; https://doi.org/10.3390/biomedicines12112522 - 4 Nov 2024
Cited by 4 | Viewed by 1386
Abstract
Background: Topical applications have long been regarded as precise methods for delivering drugs to soft tissues, such as the periodontal ligament, as well as hard structures, including the alveolar bone and cementum. Recently, the combination of hyaluronic acid (HA) and ozone therapy has [...] Read more.
Background: Topical applications have long been regarded as precise methods for delivering drugs to soft tissues, such as the periodontal ligament, as well as hard structures, including the alveolar bone and cementum. Recently, the combination of hyaluronic acid (HA) and ozone therapy has gained popularity as a supportive treatment for chronic inflammation, in addition to its established role in enhancing healing after dental procedures. Methods: To gather the necessary research for our study, we conducted a systematic search across several databases, including PubMed, Google Scholar, and Ovid. Our study was registered under Prospero number CRD42024569641. The research, which began in June 2015 and concluded in May 2024, systematically examined the potential benefits of topical HA application in the management of both acute and chronic inflammatory diseases. Using relevant keywords and Medical Subject Headings, we selected 28 pertinent studies: three related to gingivitis, thirteen on chronic periodontitis, seven involving dental surgeries such as implants and sinus lifts, and three on oral ulcers. Results: The risk of bias among the analyzed studies was assessed using the RoB 2 tool. Regarding the randomization process, 75% of the studies exhibited a high risk of bias. However, all studies (100%) had a low risk of bias concerning allocation concealment. Only 25% of the studies adequately addressed performance bias, and another 25% reported all outcome data. Nevertheless, 85% of the included studies showed a low risk of reporting bias. Conclusions: The results indicate that the use of topical HA in combination with ozone therapy is highly effective not only in promoting post-operative healing following dental procedures but also in providing positive outcomes for individuals dealing with chronic gingivitis, periodontal inflammation, and oral ulcers. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)
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Review

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21 pages, 379 KiB  
Review
Dysbiosis of Oral Microbiome: A Key Player in Oral Carcinogenesis? A Critical Review
by K. Devaraja and Sadhna Aggarwal
Biomedicines 2025, 13(2), 448; https://doi.org/10.3390/biomedicines13020448 - 12 Feb 2025
Viewed by 1238
Abstract
The oral cavity is known to harbor hundreds of microorganisms, belonging to various genera, constituting a peculiar flora called the oral microbiome. The change in the relative distribution of the constituents of this microbial flora, due to any reason, leads to oral dysbiosis. [...] Read more.
The oral cavity is known to harbor hundreds of microorganisms, belonging to various genera, constituting a peculiar flora called the oral microbiome. The change in the relative distribution of the constituents of this microbial flora, due to any reason, leads to oral dysbiosis. For centuries, oral dysbiosis has been linked to the etiopathogenesis of several medical illnesses, both locally and systemically-. However, aided by the recent advent of bio-technological capabilities, several reports have re-emerged that link oral dysbiosis to oral carcinogenesis, and numerous studies are currently exploring their association and plausible mechanisms. Some of the proposed mechanisms of oral dysbiosis-induced carcinogenesis (ODIC) include—a bacteria-induced chronic inflammatory state leading to direct cellular damage, inflammatory-cytokine-mediated promotion of cellular proliferation and invasion, release of bacterial products that are carcinogenic, and suppression of local immunity by alteration of the tumor microenvironment. However, the actual interactions between these cellular mechanisms and their role in carcinogenesis are not yet fully understood. This review provides a comprehensive overview of the various hypotheses and mechanisms implicated in the ODIC, along with the corresponding molecular aberrations. Apart from discussing the usual constituents of the oral microbiome profile, the review also summarizes the various dysbiosis profiles implicated in ODIC. The review also sheds light on the potential clinical implications of the research on oral microbiome in the prevention and management of oral cancer. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)

Other

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15 pages, 413 KiB  
Systematic Review
The Use of Hyaluronic Acid in the Non-Surgical Treatment of Periodontitis—An Umbrella Review
by Wojciech Niemczyk, Jacek Matys, Rafał Wiench, Jacek Żurek and Marzena Dominiak
Biomedicines 2025, 13(4), 998; https://doi.org/10.3390/biomedicines13040998 - 20 Apr 2025
Cited by 1 | Viewed by 286
Abstract
Background: Periodontitis is a prevalent inflammatory condition that destroys periodontal tissues. Scaling and root planing (SRP) is the gold standard for non-surgical treatment; however, its efficacy may be limited in cases with complex dental issues. This umbrella review aims to evaluate the [...] Read more.
Background: Periodontitis is a prevalent inflammatory condition that destroys periodontal tissues. Scaling and root planing (SRP) is the gold standard for non-surgical treatment; however, its efficacy may be limited in cases with complex dental issues. This umbrella review aims to evaluate the effectiveness of hyaluronic acid (HA) as an adjunct to scaling and root planing (SRP) in enhancing clinical outcomes for periodontitis management. Methods: A comprehensive review of five systematic reviews, including meta-analyses where available, was conducted to synthesize evidence on the adjunctive use of HA with SRP. The studies were evaluated using the AMSTAR-2 quality assessment tool to determine methodological rigor. Data on clinical parameters such as probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), and plaque index (PI) were extracted and analyzed. Results: The findings indicate that HA supplementation leads to moderate improvements in PD, CAL, BOP, GI, and PI compared to SRP alone. Notable reductions in PD and gains in CAL were observed, with some meta-analyses showing statistically significant benefits. However, the heterogeneity in HA concentrations (0.2–1.4%), application methods, treatment frequencies, and follow-up durations (1 week to 12 months) limits definitive conclusions. Additionally, HA did not significantly affect the reduction in P. gingivalis prevalence. Conclusions: The use of HA in conjunction with SRP shows promise in enhancing the efficacy of non-surgical periodontal therapy. However, the heterogeneity in the quality and methodologies of the studies indicates the necessity for high-quality, standardized randomized controlled trials to establish clear clinical guidelines for the application of HA in the treatment of periodontitis. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)
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10 pages, 1076 KiB  
Systematic Review
The Role of Hyaluronic Acid in Alveolar Ridge Preservation: A Systematic Review of Its Biological and Regenerative Potential According to PRISMA Guidelines and the Cochrane Handbook
by Vincenzo Ronsivalle, Simona Santonocito, Roberta Giudice, Salvatore Bocchieri, Simone Didomenico and Marco Cicciù
Biomedicines 2025, 13(2), 451; https://doi.org/10.3390/biomedicines13020451 - 12 Feb 2025
Viewed by 899
Abstract
Objectives: This systematic review evaluates the biological activity and regenerative potential of hyaluronic acid (HA) in alveolar ridge preservation (ARP) following tooth extraction, assessing its efficacy in reducing bone resorption and promoting bone regeneration when combined with xenografts. Methods: A comprehensive [...] Read more.
Objectives: This systematic review evaluates the biological activity and regenerative potential of hyaluronic acid (HA) in alveolar ridge preservation (ARP) following tooth extraction, assessing its efficacy in reducing bone resorption and promoting bone regeneration when combined with xenografts. Methods: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and Lilacs databases, adhering to PRISMA guidelines. Studies from 2012 to December 2024 involving human participants were included based on a PECO framework. Four studies met the inclusion criteria, with data extracted and analyzed for clinical and histological outcomes. The risk of bias was assessed using the ROBINS-E tool. Results: The included studies demonstrated that HA combined with xenografts significantly reduced post-extraction bone resorption compared to controls. HA-enhanced grafts showed superior radiographic and histological outcomes, including increased bone density and reduced graft shrinkage. While one randomized controlled trial found no significant differences in wound healing or patient-reported outcomes between HA and control groups, other studies reported improved bone formation and graft stability with HA. Variability in study design and sample size was noted, with a generally moderate to high risk of bias in some studies. Conclusions: The evidence supports the beneficial role of HA as an adjuvant in ARP procedures, enhancing bone regeneration and limiting resorption. However, further research with larger samples and standardized methodologies is required to confirm these findings and optimize clinical protocols. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)
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