Characterization of oral biomarkers during early healing at augmented dental implant sites.

AIM: The aim of this study is to assess early wound healing expression of local angiogenic biomarkers following connective tissue graft (CTG) at dental implant sites. METHODS: Twenty-eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or with tunnel technique (TUN). Peri-implant crevicular fluid (PICF) was collected at the midfacial and midlingual aspect of the implant sites at baseline and at 3, 7, 14, 30, and 90 days after the surgical intervention. The expression of angiogenin (ANG), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinases-2 (TIMP-2), and vascular endothelial growth factor (VEGF) was investigated over a period of 3 months. Patient-reported outcomes, clinical measurements, and ultrasonography scans at multiple time points were also evaluated. RESULTS: The longitudinal regression revealed a significant difference in the expression of VEGF and TIMP-2 between CAF- and TUN-treated sites over 3 months (p = .033 and p = .004, respectively), whereas no significant differences were observed for ANG, FGF-2 and PDGF between the two groups. At 7 days, a direct correlation was observed between ANG levels and ultrasonographic color velocity in the CAF group (p < .001) and between ANG levels and ultrasonographic color power in the TUN group (p = .028). VEGF levels and ultrasonographic mean perfused area of the CTG were significantly correlated at the 7-day time point (p < .001 for both CAF and TUN). The expression of VEGF at 7 days was directly associated with mucosal thickness gain at 1 year (p < .001 for both groups). Early TIMP-2 expression showed an inverse correlation with time to recovery (p = .002). TIMP-2 levels at 3 months exhibited inverse correlations with mean dehiscence coverage (p = .004) and the rate of complete dehiscence coverage (p = .012). CONCLUSION: PICF biomarkers can be used to monitor early wound healing events following soft tissue grafting at implant sites. VEGF and TIMP-2 showed correlations with the 1-year clinical and volumetric outcomes, as well as with post-operative patient-reported outcomes and Doppler Ultrasonographic tissue perfusion-related parameters.

Recombinant human platelet-derived growth factor improves root coverage of a collagen matrix for multiple adjacent gingival recessions: A triple-blinded, randomized, placebo-controlled trial.

AIM: To evaluate the efficacy of recombinant human platelet-derived growth factor (rhPDGF)-BB combined with a cross-linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF). MATERIALS AND METHODS: Thirty patients were enrolled in this triple-blind, randomized, placebo-controlled trial and treated with either CAF + CCM + rhPDGF, or CAF + CCM + saline. The primary outcome was mean root coverage (mRC) at 6 months. Complete root coverage, gain in gingival thickness (GT), keratinized tissue width, volumetric and ultrasonographic changes, and patient-reported outcome measures were also assessed. Mixed-modelling regression analyses were used for statistical comparisons. RESULTS: At 6 months, the mRC of the CCM + rhPDGF and CCM alone groups were 88.25% and 77.72%, respectively (p = .02). A significant gain in GT was consistently observed for both treatment arms, and more so for the patients receiving the matrix containing rhPDGF through time (0.51 vs. 0.80 mm, on average, p = .01). The rhPDGF + CCM treated patients presented greater volume gain, higher soft tissue thickness, and a superior aesthetic score. CONCLUSION: rhPDGF enhances the clinical, volumetric, and aesthetic outcomes of MAGRs above the results achieved with CAF + CCM alone (ClinicalTrials.gov NCT04462237).

Crevicular fluid biomarkers and periodontal disease progression.

AIM: Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). MATERIALS AND METHODS: In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1ß. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. RESULTS: Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). CONCLUSIONS: Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745).

Pro-inflammatory profiles in cardiovascular disease patients with peri-implantitis.

BACKGROUND: To investigate the pro-inflammatory cytokine profiles in patients with or without cardiovascular disease (CVD) and with or without peri-implantitis. METHODS: Serum, peri-implant crevicular fluid (PICF), and gingival crevicular fluid (GCF) were collected from patients with (n = 82) or without CVD (n = 46) at the most severe peri-implantitis site including sites with periodontitis. A panel of proinflammatory molecules including high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-1 beta (IL-1ß), IL-6, plasma tumor necrosis factor-alpha (TNF-α), matrix metallo-proteinase-8 (MMP-8), osteoprotegerin (OPG), vascular endothelial growth factor (VEGF), IL-17, IL-8, tissue inhibitor of metalloproteinase-2 (TIMP-2), myeloperoxidase (MPO), and prostaglandin E2 (PGE2 ) were analyzed using human custom Quantibody arrays. Krunskal-Wallis test was used to compare groups. The diagnostic ability of each biomarker was assessed using chi-square test and ROC analysis. RESULTS: Serum IL-1ß, TNF-α and fibrinogen were significantly higher in CVD patients than those without. Serum fibrinogen displayed a trend of higher concentration in patients with radiographic bone loss (RBL) ≥2 mm (P = 0.08). PICF TNF-α exhibited a significantly higher detection level in the CVD patients that is coincided with the local peri-implant inflammation. In addition, PICF MMP-8 was significantly higher in the RBL ≥2 mm sites than the healthy implants; whereas IL-1ß, IL-8, MMP-8, and TIMP-2 proved to be the significant predictors for peri-implant disease. GCF TNF-α collected from patients with periodontitis was significantly associated with CVD cases. CONCLUSION: The augmented expression of local and systemic pro-inflammatory cytokines found in the current study supports the weak association between the chronic peri-implantitis with increasing severity and CVD.

Effects of food supplements on periodontal status and local and systemic inflammation after nonoperative periodontal treatment.

The present study aimed to assess the effects of a multimicronutrient food supplement on periodontal clinical parameters and systemic/local inflammatory markers. Thirty patients with severe chronic periodontitis who adhered to the Mediterranean diet (MD) underwent non-surgical therapy and daily took either the micronutrient complex (group-A) or olive oil (group-B) from baseline (T0) to 3 months (T2). Supragingival debridement was performed at T0. One month later (T1), one-stage-full-mouth disinfection was performed. Periodontal clinical parameters were monitored and correlated with serum C-reactive protein (CRP) and salivary matrix metalloproteinase-8/9 (MMPs-8/9) quantified at each time point. Longitudinal analysis revealed that in group-A, the MMP-8/-9 levels were decreased at T2 compared with at T0 (P = 0.013 and P = 0.004, respectively) and that the MMP-9 levels were decreased at T1 (P = 0.004). These reductions were not significant in group-B. The CRP levels in both groups did not change over time. No between-group differences were noted for any parameter. The correlation between the full-mouth bleeding score and the MMP-8 level in both groups was significant (P < 0.001). The investigated local and systemic inflammatory parameters were not affected by the tested multimicronutrient supplement in patients who adhered to MD. In conclusion, MMP-8 is useful for assessing the reduction in periodontal inflammation.

Characterization of ligature-induced experimental periodontitis.

We sought to better characterize the progression of periodontal tissue breakdown in rats induced by a ligature model of experimental periodontal disease (PD). A total of 60 male Sprague-Dawley rats were evenly divided into an untreated control group and a PD group induced by ligature bilaterally around first and second maxillary molars. Animals were sacrificed at 1, 3, 5, 7, 14, and 21 days after the induction of PD. Alveolar bone loss was evaluated by histomorphometry and microcomputed tomography (µCT). The immune-inflammatory process in the periodontal tissue was assessed using descriptive histologic analysis and quantitative polymerase chain reaction (qPCR). This ligature model resulted in significant alveolar bone loss and increased inflammatory process of the periodontal tissues during the initial periods of evaluation (0-14 days). A significant increase in the gene expression of pro-inflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and proteins involved in osteoclastogenesis, receptor activator of nuclear factor-k B ligand (RANKL) and osteoprotegerin (OPG) was observed in the first week of analysis. In the later periods of evaluation (14-21 days), no significant alterations were noted with regard to inflammatory processes, bone resorption, and expression of cytokine genes. The ligature-induced PD model resulted in progressive alveolar bone resorption with two different phases: Acute (0-14 days), characterized by inflammation and rapid bone resorption, and chronic (14-21 days) with no significant progression of bone loss. Furthermore, the gene expressions of IL-6, IL-1ß, TNF-α, RANKL, and OPG were highly increased during the progress of PD in the early periods. RESEARCH HIGHLIGHTS: Ligature-induced bone resorption in rats occurred in the initial periods after disease induction The bone resorption was characterized by two distinct phases: Acute (0-14 days), with pronounced inflammation and alveolar bone loss Chronic phase (14-21 days): No further disease progression Several pro-inflammatory cytokines were increased during the progress of periodontitis.