Histologic Evaluation of Early Papilla Healing after Augmentation with Injectable Hyaluronic Acid-A Proof of Concept.

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.

Clinical and Radiographic Evaluation of Intrabony Periodontal Defects Treated with Hyaluronic Acid or Enamel Matrix Proteins: A 6-Month Prospective Study.

PURPOSE: To compare the regenerative clinical and radiographic effects of cross-linked hyaluronic acid (xHyA) with enamel matrix proteins (EMD) at six months after regenerative treatment of periodontal intrabony defects. MATERIALS AND METHODS: Sixty patients presenting one intrabony defect each were randomly assigned into control (EMD) and test (xHyA) groups. Clinical attachment level (CAL) gain was the primary outcome, while pocket probing depth (PPD), gingival recession (REC), bleeding on probing (BOP), full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and radiographic parameters such as defect depth (BC-BD), and defect width (DW) were considered secondary outcome variables. Parameters were recorded at baseline and after 6 months. RESULTS: At the 6-month follow-up, 54 patients were available for statistical analysis. In the control and test groups, the mean CAL gain was statistically significant in the intragroup comparison (p < 0.001). 48.1% of test sites showed a CAL gain ≤ 2 mm compared with 33.3% of control sites. The mean PPD reduction was statistically significant in the intragroup comparison in both groups (p < 0.001). The mean REC increase was similar in the two groups: 1.04 ± 1.29 mm vs 1.11 ± 1.22 mm (test vs control). The mean BC-BD, DW, FMPS, FMBS, and BOP changed statistically significantly only in the intragroup comparison, not in the intergroup comparison. CONCLUSION: Both treatments, EMD and xHyA, produced similar statistically significant clinical and radiographical improvements after six months when compared with baseline.

Comparative Study of Systemic vs. Local Antibiotics with Subgingival Instrumentation in Stage III-IV Periodontitis: A Retrospective Analysis.

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.

A Low-Cost Protocol Using the Adjunctive Action of Povidone-Iodine Irrigations and Sodium Hypochlorite Rinsing Solution in Step 2 of Periodontal Therapy for Patients with Stage III-IV Periodontitis: A Single-Blind, Randomized Controlled Trial.

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.

Healing of Periodontal Suprabony Defects following Treatment with Open Flap Debridement with or without Hyaluronic Acid (HA) Application.

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.

A Single Dose of Piperacillin Plus Tazobactam Gel as an Adjunct to Professional Mechanical Plaque Removal (PMPR) in Patients with Peri-Implant Mucositis: A 6-Month Double-Blind Randomized Clinical Trial.

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.

Clinical and Radiological Characterization of the Long-Term Association between Unaffected/Minimally Affected Implants and History of Severe Periodontitis: A Retrospective Study.

OBJECTIVES: The objectives of this research were to compare, retrospectively, the clinical and radiographic modifications of periodontal parameters and peri-implant conditions and to analyze the relationship between the changes in periodontal parameters and peri-implant conditions over a mean follow-up period of 7.6 years in a treated population with progressive/uncontrolled periodontitis and at least one unaffected/minimally affected implant. MATERIALS AND METHODS: Nineteen partially edentulous patients having 77 implants inserted, with a mean age of 54.84 ± 7.60 years, were matched for age, gender, compliance, smoking status, general health, and implant characteristics. Periodontal parameters were evaluated in the remaining teeth. Means per teeth and implants were used when making comparisons. RESULTS: Statistically significant differences were observed between baseline and final examination in teeth for tPPD, tCAL and MBL. Furthermore, at 7.6 years, statistically significant differences existed between implants and teeth with regard to iCAL and tCAL (p = 0.03). Multiple regression analyses were performed and revealed a significant association regarding iPPD and CBL with smoking and periodontal diagnosis. In addition, FMBS was significantly associated with CBL. Unaffected/minimally affected implants were found more frequently in the posterior mandible, with longer lengths (>10 mm) and small diameters (<4 mm), including in screwed multi-unit bridges. CONCLUSIONS: The study results appear to reflect minimally affected mean crestal bone-level loss around implants in comparison to the marginal bone-level loss around teeth when exposed to uncontrolled severe periodontal disease over a mean period of observation of 7.6 years, while the unaffected/minimally affected implants seemed to benefit from a combination of clinical factors, including posterior mandibular position, smaller diameters, and screwed multi-unit restorations.

Influence of Section Thickness on the Accuracy and Specificity of Histometric Parameters Using Confocal Laser Scanning Microscopy in a Canine Model of Experimental Peri-Implantitis-A Proof of Concept.

OBJECTIVES: Tissue breakdown was assessed by confocal laser scanning microscopy (CLSM) using autofluorescence around implants with ligatures, on a dog hemimandible. Influence of section thickness on the accuracy of histometrical observations was also evaluated, in comparison with thin sections in light microscopy. MATERIAL AND METHODS: Three months after tooth extraction, implants were placed. Two months after abutment placement, ligatures were placed with no plaque control. 11 months post-implantation, the animal was sacrificed. Undecalcified thin (30 µm) sections were cut, stained and evaluated by light microscopy to be used as a reference. Additional sections were performed, so that another pair of unstained thick sections resulted (250-300 µm). Tissue loss was assessed using histomorphometric parameters under CLSM and was compared to the light microscopy reference ones. RESULTS: Morphometry confirmed tissue loss more pronounced on the "thick" and quick sections, when compared to the time-consuming and technique-sensitive "thin" ones. CONCLUSIONS: Within the limits of the present study, the adequacy of histometrical observations under CLSM reveal commensurable information about soft-tissue-bone-implant details, when compared to traditional light microscopy histological protocols. The CLSM investigation may seem demanding, yet the richness of data acquired may justify this approach, provided seatbacks caused by improper manipulation of "thick" sections are avoided.

A Placebo-Controlled Trial to Evaluate Two Locally Delivered Antibiotic Gels (Piperacillin Plus Tazobactam vs. Doxycycline) in Stage III-IV Periodontitis Patients.

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.

Is the Diagnosis of Generalized Stage IV (Severe) Periodontitis Compatible with the Survival of Extended Stabilizing Prosthetic Restorations? A Medium-Term Retrospective Study.

The aim of the study was to identify the most relevant patient-related factors directly involved (alone or in combinations) in the long-term survival and functionality of the abutment teeth of extensive stabilizing bridges and removable prosthesis, in patients treated for Stage IV periodontitis, adhering to SPT over a period of at least 5 years. Seventy-six patients treated between 2000-2022, rehabilitated with FDPs and RDPs, adhering to SPT for at least 5 years were included. Patient-related factors influencing retention of RDPs and FDP, survival rates in regular (RCs) and irregular compliers (ICs), and incidence of biological and technical complications were assessed. During a follow-up of 69 months, from 57 patients with FDPs and 19 patients with RDPs, 39 (51.32%) were ICs, while 37 (48.68%) were RCs. An overall statistically significant association (p = 0.04) was identified between biological complications and the type of prostheses. The RDP patients had more complications than FDP patients. In 5.26% of the RDP patients, root caries were identified, and 10.53% were diagnosed with a periapical (endodontic) lesion, while 3.51% of the FDPS patients presented root caries. In five (6.57%) cases, abutment loss resulted in the loss of the prosthesis. Statistically significant correlations were observed between systemic diseases and tooth loss, and between type of tooth lost and the reason for tooth loss, irrespective of the type of prosthesis. A total of 66.67% of the lost incisors, 85.71% of the lost premolars, and 88.89% of the lost molars occurred due to periodontal causes. Furthermore, 93% of the FDPs and RDPs were still in place and in function.

Clinical and microbiological effects of a single application of sodium hypochlorite gel during subgingival re-instrumentation: a triple-blind randomized placebo-controlled clinical trial.

OBJECTIVES: The aim of this study is to assess the clinical and microbiological effects of a single subgingival administration of sodium hypochlorite gel (NaOCl) and compare it with 1% chlorhexidine (CHX) gel and a placebo gel following mechanical re-instrumentation during supportive periodontal therapy (SPT). MATERIALS AND METHODS: Sixty-two patients who had been treated for stage III-IV periodontitis and enrolled in SPT were included in the study based on following criteria: (1) active periodontal therapy completed at least 6 months before enrollment in the study, (2) presence of at least 4 non-adjacent sites with probing pocket depths (PPDs) ≥ 4 mm with bleeding on probing (BOP), or presence of 5-8 mm PPDs with or without BOP. All sites presenting PPD ≥ 4 mm and BOP at baseline and 3-, 6-, and 9-month follow-up timepoints were subgingivally re-instrumented with ultrasounds. Selected patients were randomly assigned into three groups and treated additionally with a single subgingival administration of NaOCl gel (group A); 1% CHX gel (group B); and placebo gel (group C). Main outcome variable was pocket closure at 12 months. Secondary outcome variables were changes in mean PPD, BOP, and clinical attachment level (CAL) along with changes in the numbers of the following five keystone bacterial pathogens: Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Tannerella forsythia (T.f.), and Treponema denticola (T.d.). RESULTS: At 12 months, pocket closure was obtained in 77.5% in the NaOCl treated sites. The reduction in PPD was higher with CHX than with NaOCl, although a statistically significant adjunctive effect for NaOCl (P = 0.028) was only observed in comparison with placebo only. Mean CAL improved in all groups and at all timepoints, compared to the baseline (P < 0.05). However, after 6 months, CAL gain was statistically significantly higher in the NaOCl treated group than following application of CHX (P = 0.0026). CONCLUSION: In SPT patients, a single adjunctive use of a NaOCl gel may provide benefits in controlling inflammation and residual pockets. TRIAL REGISTRATION: ISRCTN Registry of Clinical Trials (ISRCTN11387188). CLINICAL RELEVANCE: A baseline single application of NaOCl gel in conjunction with mechanical debridement may achieve substantial pocket closure in patients enrolled in SPT; treatment time, cost, and applicability considerations should be taken into account when selecting this therapy.

Comparison of three full-mouth concepts for the non-surgical treatment of stage III and IV periodontitis: A randomized controlled trial.

AIM: To evaluate the clinical efficacy of full-mouth scaling (FMS), full-mouth disinfection (FMD), and FMD with adjuvant erythritol air-polishing (FMDAP) compared to quadrant-wise debridement (Q-SRP) in patients with periodontitis stage III/IV. METHODS: In this four-arm parallel, prospective, randomized, controlled multi-centre study, changes of pocket probing depths (PPDs), clinical attachment level (CAL), bleeding on probing (BOP), and proportion of closed pockets (PPD ≤4 mm without BOP) were evaluated at baseline and after 3 and 6 months. RESULTS: From 190 randomly participating patients, 172 were included in the final analysis. All groups showed significant (p < .05) improvements in all clinical parameters over 3 and 6 months. During the study period, FMDAP showed significantly higher reductions of mean PPD in teeth with moderate (PPD 4-6 mm) and deep (PPD > 6 mm) pockets and significantly increased proportions of pocket closure than Q-SRP. Patients treated with FMD had significantly greater PPD reduction in deep pockets and a higher percentage of pocket closure after 3 months but not after 6 months compared to Q-SRP. CAL and BOP changes did not significantly differ among all groups. Efficiency of treatment (time effort to gain one closed pocket) was significantly higher for FMDAP, FMD, and FMS compared to Q-SRP (6.3, 8.5, 9.5 vs. 17.8 min per closed pocket; p < .05). CONCLUSIONS: All treatment modalities were effective, without significant differences between full-mouth approaches. FMDAP showed improved clinical outcomes over Q-SRP for moderate and deep pockets after 6 months. Full-mouth protocols were more time-efficient than conventional Q-SRP. CLINICAL SIGNIFICANCE: The trial was registered in a clinical trial database (ClinicalTrials.gov: NCT03509233).

Evaluation of oral keratinocyte progenitor and T-lymphocite cells response during early healing after augmentation of keratinized gingiva with a 3D collagen matrix - a pilot study.

BACKGROUND: The aim of the present study is to analyze the behavior of selected populations of oral keratinocytes and T-lymphocytes, responsible for re-constructing and maintaining the oral epithelial tissue architecture, following augmentation of the keratinized oral mucosa using a 3D-collagen matrix. METHODS: Different groups of oral keratinocytes were isolated from biopsies harvested from 3 patients before the surgical procedure, as well as 7 and 14 days after the augmentation procedure. T-lymphocytes were isolated from peripheral blood at same timepoints. Keratinocytes were characterized for stem and differentiation markers, such as p63, cytokeratin 10 and 14, and in vitro parameters, such as cell viability, cell size and colony-forming efficiency. T-lymphocytes were analyzed for viability and the expression of various cluster of differentiation markers. The methods included magnetic separation of cell populations, immunofluorescence, flow cytometry, and histology of oral biopsies. RESULTS: Both at 7 and 14 days, the majority of cells that repopulate the matrix were actively proliferating/progenitor oral keratinocytes with the phenotype integrin alfa6beta4 + CD71+. These cells display in vitro characteristics similar to the progenitor cells analyzed before the matrix placement. T-lymphocytes expressed CD8 and CD69 markers, while CD25 was absent. CONCLUSION: The study shows that two weeks after the collagen membrane placement, the healing process appeared to be histologically complete, with no abnormal immune response induced by the matrix, however, with a higher than usual content of active proliferating cells, the majority of keratinocytes being characterized as transit amplifying cells.