Darian Rusu

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: Less often employed as a rinsing solution for controlling oral biofilms, NaOCL was used in oral rinses at various concentrations in steps 1 and 4 of periodontal therapy. The aim of this study was to quantitatively evaluate the biofilm-disruptive properties of a 0.2% NaOCl solution in standardized oral rinses using dedicated plaque-disclosing agents and 3D scanning methods in patients undergoing the regular Guided Biofilm Therapy^® protocol. Methods: Eight patients with at least 20 teeth present evenly distributed between the two arches were included. After 24 h of refraining from oral hygiene, dental arches were stained with a disclosing agent, the subjects rinsed for 20 s, clinical photographs and 3D scans were performed, subjects rinsed again for 20 s, photographs and 3D scans were performed again, and then the GBT^® protocol was resumed as usual. Data representing areas covered with dental plaque were acquired using the “Medit Scan for Clinics” software and then underwent a post-processing and rendering process. The outcome variable was the percent reduction in the plaque-covered areas. Results: For the upper jaw, the estimated mean percent reduction in the biofilm-covered area was 39.65%, while for the mandible, it was 38.26%. The analysis of individual photographs revealed changes in the plaque-covered areas and reductions in the color intensity of the residual plaque-covered areas under identical lighting conditions. Conclusions: When analyzed using 3D intraoral scanning, the 0.2% NaOCl rinsing solution seems to be a clinically efficient disruptor/dissolvent of the oral biofilm, both when integrated into modern protocols of periodontal therapy like GBT^® and for home self-care.

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.

Background and Objectives: This randomized, double-arm, multicentric clinical trial aims to compare the clinical outcomes following the treatment of suprabony periodontal defects using open flap debridement (OFD) with or without the application of hyaluronic acid (HA). Materials and Methods: Sixty systemically healthy patients with at least two teeth presenting suprabony periodontal defects were randomly assigned with a 1:1 allocation ratio using computer-generated tables into a test (OFD + HA) or control group (OFD). The main outcome variable was clinical attachment level (CAL). The secondary outcome variables were changes in mean probing pocket depth (PPD), gingival recession (GR), full-mouth plaque score (FMPS), and full-mouth bleeding score (FMBS). All clinical measurements were carried out at baseline and 12 months. Results: Sixty patients, thirty in each group, were available for statistical analysis. The mean CAL gain was statistically significantly different (p < 0.001) in the test group compared with the control group (3.06 ± 1.13 mm vs. 1.44 ± 1.07 mm). PPD reduction of test group measurements (3.28 ± 1.14 mm) versus the control group measurements (2.61 ± 1.22 mm) were statistically significant (p = 0.032). GR changes were statistically significant only in the test group 0.74 ± 1.03 mm (p < 0.001). FMBS and FMPS revealed a statistically significant improvement mostly in the test group. Conclusions: Suprabony periodontal defects could benefit from the additional application of HA in conjunction with OFD in terms of improvement of the clinical parameters compared with OFD alone.

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.

To improve the clinical and microbiological outcomes of non-surgical mechanical periodontal therapy, the adjunctive use of antimicrobials has been utilized in treating moderate-to-severe periodontitis. In our study, the retrospective design included previously collected health-related patient data, obtained from the printed and digital charts of patients who received systemic or local antibiotic adjuncts to SI (subgingival instrumentation). A total of 34 patients (diagnosed with generalized Stage III/IV periodontitis) met the inclusion and exclusion criteria and were evaluated. The samples were tested for the following bacterial strains: Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), Prevotella intermedia (P. intermedia), Tanererella forsythia (T. forsythia), and Treponema denticola (T. denticola). The inter-group comparisons of the bacterial species did not show statistically significant differences between groups. The present study aimed to evaluate the clinical effects after SI and the adjunctive use of systemically administered (SA) AMX (amoxicillin) + MET (metronidazole) (administered for 7 days), with locally delivered (LDD) piperacillin + tazobactam in step 2 of periodontal therapy. Results: Overall, all parameters were improved in the groups, with a significant difference in inter-group comparison regarding the full-mouth bleeding score (FMBS) (p < 0.05) in favor of the SA group, and the p-value < 0.05 was considered to be statistically significant. Statistically significant PPD (probing pocket depth) reductions and CAL (clinical attachment level) gains were observed in both groups at the 3-month follow-up. In conclusion, within the limitations, the outcomes of this study suggest that SI, with adjunctive local or systemic antibiotic therapy, provided comparable clinical improvements. Systemic AMX + MET protocols were more efficacious with regard to the reduction in FMBS. Follow-up studies with larger patient numbers are needed to further investigate this effect.

Objectives: This randomized, placebo-controlled, double-masked clinical trial aimed to evaluate the clinical and microbiological efficacy of professional mechanical plaque removal (PMPR) with or without adjunctive application of piperacillin plus tazobactam gel in the treatment of peri-implant mucositis (PiM) for up to 6 months. Materials and Methods: The study included 31 patients with peri-implant mucositis (bleeding on probing (BoP) > 1 at at least one site at baseline, absence of peri-implant bone loss compared with a previous radiograph). After randomized assignment to test and control groups, patients received full-mouth supragingival scaling with or without piperacillin plus tazobactam gel. Clinical examination was performed at baseline and after 3 and 6 months, and a microbiological examination was performed at baseline and after 3 months. Results: After six months, both treatment modalities resulted in significant reductions and improvements in clinical parameters at the implant sites. Neither study group achieved a complete resolution of PiM (i.e., BoP ≤ 1 per implant). The number of implants with BoP decreased statistically significantly between subsequent time points (p < 0.001) in both the test and the control group. Significant BoP differences (p = 0.039) were observed between groups at 6 months (difference to baseline) following therapy. Conclusions: Within the limitations of the present study, the single use of a slow-release, locally applied antibiotic combination of piperacillin and tazobactam gel, adjunctive to PMPR, showed an improvement in clinical variable of implants diagnosed with PiM. The adjunctive treatment resulted in higher BoP reduction when compared to the control, but no significant differences were observed regarding the changes in other clinical and microbiological parameters.

This randomized, split-mouth, controlled clinical study assessed the additional clinical benefits of a local desiccant antimicrobial agent (HY) combined with subgingival mechanical instrumentation (SRP) vs. SRP alone in treating severe periodontitis. Patients with stages III and IV periodontitis received full-mouth periodontal examinations at baseline and after a three-month follow-up. Two randomly selected hemiarches in each periodontitis patient were treated with SRP plus HY and were included in the test group, while the other two hemiarches received only SRP and were included in the control group. In thirty patients, the analyses of the evolution of the periodontal parameters over time showed statistically significant mean differences for the probing depths and clinical attachment level values resulting from all the examined sites, as well as from the interproximal sites (p < 0.001) in both the test and control groups. The intergroup comparisons of the same four parameters showed no significant differences (p = 0.322, p = 0.36, p = 0.516, and p = 0.509, respectively). Based on these study results, no additional benefits were obtained after HY subgingival applications.

Placing antimicrobial treatments directly in periodontal pockets is an example of the local administration of antimicrobial drugs to treat periodontitis. This method of therapy is advantageous since the drug concentration after application far surpasses the minimum inhibitory concentration (MIC) and lasts for a number of weeks. As a result, numerous local drug delivery systems (LDDSs) utilizing various antibiotics or antiseptics have been created. There is constant effort to develop novel formulations for the localized administration of periodontitis treatments, some of which have failed to show any efficacy while others show promise. Thus, future research should focus on the way LDDSs can be personalized in order to optimize future clinical protocols in periodontal therapy.

Background and objectives: this study aims to evaluate the clinical and microbiological effects of a single subgingival administration of a locally delivered antibiotic gel containing piperacillin plus tazobactam and compare it with a slow-release doxycycline (14%) gel and a placebo gel, following subgingival instrumentation (SI) in patients with severe periodontitis. Materials and methods: sixty-four patients diagnosed with stage III–IV periodontitis were enrolled, were randomly assigned into three groups, and were treated additionally with a single subgingival administration of piperacillin plus tazobactam gel (group A); doxycycline gel (group B); and placebo gel (group C). The primary outcome variable was the change in mean probing pocket depth (PPD) 6 months after the intervention. Secondary outcome variables were changes in mean full-mouth bleeding score (FMBS); full-mouth plaque score (FMPS); overall bleeding index (BOP); pocket closure; and clinical attachment level (CAL), along with changes in the numbers of five keystone bacteria: Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Tannerella forsythia (T.f.), and Treponema denticola (T.d.). Intergroup and intragroup differences were evaluated at 3 and 6 months. Results: at baseline, the three groups were comparable. An improvement in clinical parameters such as PPD, CAL, and BOP between groups was observed at 3 and 6 months, but without statistical significance (p > 0.05). At 6 months, the intragroup analysis showed a significant reduction in clinical parameters. Even though the piperacillin plus tazobactam group showed slightly higher PPD reduction, this was not statistically significant when compared to both control groups. Conclusions: The groups had similar results, and subgingival instrumentation can be executed without adjunctive antimicrobials, reducing the costs for the patient and the working time/load of the professional.