In severe stages of periodontitis, conventional periodontal therapy and maintenance care are usually insufficient due to the viral and bacterial etiology; thus, a mechanical approach alone may not be sufficient to eliminate a substantial portion of subgingival pathogens, especially in deep periodontal sites. Background and Objectives: This single-blind, randomized clinical trial aimed to compare the clinical and microbiological efficacy of a low-cost protocol using povidone–iodine and sodium hypochlorite formulations as adjuncts to non-surgical therapy for patients with stage IV periodontitis when compared with chlorhexidine, the most commonly employed substance to date for antimicrobial regimens in periodontal therapy. Materials and Methods: Forty-five patients were randomly divided into two groups: control (subgingival instrumentation, chlorhexidine-assisted) and test (antiviral medication, subgingival instrumentation with povidone–iodine, sodium hypochlorite rinsing solution, and antibiotics). Clinical measurements and microbiological analyses were performed at baseline and after three months. Results: After three months, notable differences were found in the bacterial detection scores for Porphyromonas gingivalis (a significant reduction in detection frequency was observed in the test compared to the control (p = 0.021)), and there were significant reductions in detection in the test group for Tannerella forsythia and Treponema denticola, showing undetectable levels (p < 0.0001 for both). In the test group, the pocket probing depth median value was reduced significantly (p = 0.0005); similarly, bleeding on probing showed a marked decrease (p < 0.0001). However, changes in clinical attachment loss and full-mouth plaque score were not statistically significant. Conclusions: Using the proposed protocol, substantial improvements in clinical and microbiological parameters were obtained when compared with the current antimicrobial recommendations.

Hyaluronic acid (HA) is a biologically active glycosaminoglycan with recognized roles in wound healing and inflammation modulation, and its adjunctive use in dental and periodontal therapy has gained interest, particularly in medically compromised patients. This narrative review critically evaluated preclinical and clinical evidence on locally applied HA in periodontal, oral surgical, peri-implant, and oral medicine treatments in patients with systemic conditions. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (January 2015–December 2025) identified in vivo translational studies, randomized and controlled clinical trials, and selected systematic reviews involving medically compromised populations. Qualitative synthesis focused on biological plausibility, clinical outcomes, and safety. Nine core studies were included, comprising two preclinical in vivo investigations and seven clinical trials. In diabetic models, cross-linked high-molecular-weight HA reduced macrophage infiltration and delayed collagen membrane degradation without impairing angiogenesis. Clinically, adjunctive HA use in patients with type 2 diabetes mellitus was associated with modest but statistically significant short-term improvements in clinical attachment level (CAL) and enhanced early soft tissue healing following tooth extraction. In peri-implantitis therapy and oncology-related oral complications, HA application was linked to reduced inflammatory markers, decreased lesion severity, and improved patient-reported symptoms. No systemic adverse effects were reported. Overall, HA appears to be a locally safe adjunct that may support early healing and inflammation control in medically compromised patients, although its effects are primarily short-term and do not indicate disease-modifying potential.

Background/Objectives: Gingipains produced by P. gingivalis have been shown to be directly related to periodontal tissue degradation and are significant molecular targets in therapy of periodontitis. Blocking the activity of these enzymes should reduce survival of this pathogen and mitigate the effects of inflammation in periodontitis. Therefore, gingipains inhibitors and specific antibodies could be recommended in the treatment of periodontitis. Cysteine peptidase inhibitors can be obtained by chemical synthesis, or isolated from natural raw materials. This research has the following aims: 1. to analyze in vitro the inhibition of cysteine protease activity in the gingival crevicular fluid (GCF) and 2. to compare the toxicity of natural raw inhibitors (obtained from Fallopia japonica plant and egg white) with chlorhexidine (CHX) using an MTS viability test. Methods: Samples of GCF were collected from healthy (N = 17) individuals and (N = 65) periodontal patients. Cysteine peptidase activity was inhibited by adding a solution of cystatin from egg white (with 20% glycerol), or cystatin from knotweed, or low molecular weight inhibitors (MW < 3 kDa) from egg white and knotweed against Nα-Benzoyl-DL-arginine 4-nitroanilide hydrochloride. Results: There was a statistically significant difference between the inhibition means of cysteine protease activity for the five groups (p < 0.001). Means for the four groups of patients with periodontitis were not statistically significant different from each other (p = 0.320). The inhibition rates were higher in periodontitis patients. The toxicity of knotweed cystatin inhibitor was several times lower than the toxicity of E-64d, and of CHX. Conclusion: Cysteine protease inhibitors isolated from egg or plants were non-toxic, effectively inhibited the activity of cysteine proteases in GCF, and may be a promising alternative to more toxic standard antimicrobials (CHX) in preventing periodontal tissue breakdown.

Background/Objectives: Evidence regarding the effect of malocclusion on periodontal health is contradictory. This systematic review with meta-analysis seeks to summarize the available scientific evidence on the relationship between malocclusion and periodontal health in children and adolescents. Methods: A review of four electronic databases (PubMed, Scopus, Embase, and Web of Science) was performed. Observational studies were included if they investigated the link between malocclusion and periodontal health in children and adolescents. The quality of the studies included in the review was determined using the Newcastle–Ottawa Scale (NOS). A meta-analysis was conducted on binary outcomes using random-effect models. The Grading Recommendations Assessment, Development and Evaluation (GRADE) tool was used to determine the certainty of the evidence for each outcome. Results: The initial search yielded 774 potential articles. Nineteen articles were selected for the final qualitative analysis, and four of these were included in the meta-analysis. Certain malocclusion traits appear to be associated with less favorable periodontal health indicators in children and adolescents. Quantitative synthesis restricted to studies using the Gingival Bleeding Index (GBI) suggests that malpositioned teeth, such as crowding or lack of spacing, and Class II or Class III molar relationships may be associated with a higher odds of gingivitis in individuals under 18 years of age. The overall quality of evidence of the studies was very low, according to the GRADE criteria. Conclusions: Observational cross-sectional evidence of very low certainty suggests an association between certain malocclusions (crowding, lack of spacing, Class II or Class III molar relationships) and increased odds of gingivitis in children and adolescents. Evidence regarding dental plaque accumulation is inconsistent and limited by substantial heterogeneity across studies. Causality cannot be inferred, and further high-quality longitudinal studies are required.

Objectives: This human histological study’s purpose was to histologically evaluate papillae’s healing after hyaluronic acid (HA) gel augmentation at three healing time points after one injection with hyaDENT BG^®. Methods: Fifteen papillae from two patients with stage III, grade B periodontitis have been selected for this study. Every week for three weeks, five papillae were injected once with HA gel, and during the fourth week, the papillae were surgically removed as part of step 3 of the periodontal treatment. The histological analysis was performed on fifteen papillae, with five papillae corresponding to every timepoint of healing (weeks 1, 2, and 3). The primary outcome was considered to be the newly formed collagen fibers. The presence of residual HA, the integrity of epithelium or the presence of erosions/ulcerations, the presence and characteristics of inflammatory infiltrate, the presence of granulomatous reactions, and interstitial edema were considered to be secondary outcomes. Results: From the first to the third week, newly formed connective tissue begins to appear, while the observed HA pools (vesicles) content decreases. The density of inflammatory infiltrate was higher in the first week after injection, decreasing considerably by week 3; however, it was still visible throughout the healing time points. A granulomatous reaction was present in only three samples, while no signs of ulceration or necrosis could be observed; however, epithelial erosions could be observed on some samples after the first week. Conclusions: Papila augmentation with hyaluronic acid promotes new collagen formation from the second week of healing despite some foreign body granulomatous reactions.