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Background: Choline-stabilized orthosilicic acid (CS-OSA) was previously found to stimulate bone collagen formation in osteopenia and to improve biomarkers of cartilage degradation in knee osteoarthritis. The aim of the present study was to investigate the effect of oral administration of CS-OSA on clinical symptoms of peri-implantitis and the associated bone loss., Methods: Twenty-one patients with peri-implantitis were randomized in CS-OSA or placebo groups. After initial clinical and cone beam computed tomography (CBCT) measurements [probing pocket depth (PPD), bleeding on probing (BOP), mucosal recession (REC), distance from implant shoulder to alveolar crest (IS-AC) and distance from implant shoulder to first bone-to-implant contact (IS-BIC)], flap operations were performed at the peri-implantitis sites. All patients were instructed to use either placebo or CS-OSA capsules twice a day for 1 year. Measurements were repeated 6 and 12 months after randomization., Results: The data of 18 patients (36 implants) were used in the per protocol analysis. PPD and BOP improved significantly (p < 0.05) compared to baseline for both groups after 6 and 12 months. However, REC significantly increased in the placebo group but not in the CS-OSA group. The change in REC over 6 and 12 months was significantly different between groups (p < 0.01). IS-BIC and IS-AC measurements remained stable in the CS-OSA group whereas in the placebo group, both parameters increased significantly after 6 and 12 months. The change in IS-BIC over 12 months was significantly different between groups (p < 0.05)., Conclusion: The results of this preliminary study suggest that CS-OSA may stabilize and even prevent further bone loss after surgical peri-implantitis treatment and support mucosal tissue healing. Trial registration The trial was retrospectively registered at ISRCTN registry, registration number: ISRCTN14348802, registration date: 24/06/2020., (© 2021. The Author(s).)

Despite many discoveries over the past 20 years regarding the etiopathogenesis of periodontal and peri-implant diseases, as well as significant advances in our understanding of microbial biofilms, the incidence of these pathologies continues to rise. For this reason, it was clear that other strategies were needed to eliminate biofilms. In this review, the literature database was searched for studies on locally delivered synthetic agents that exhibit anti-biofilm properties and their potential use in the treatment of two important oral diseases: periodontitis and peri-implantitis.

Background This 6-months randomized controlled clinical trial aimed to assess the efficacy of indocyanine green mediated photodynamic therapy (ICG-PDT) as an adjunct to peri‑implant manual debridement (PIMD) versus PIMD alone among Diabetes Mellitus (DM) patients in the treatment of peri‑implantitis. Methods A total of 48 DM patients having 64 implants were treated with either ICG-PDT + PIMD (n = 35 implants) or PIMD alone (n = 29 implants). Clinical (probing depth [PD], bleeding on probing [BOP], and plaque index [PI]) and radiographic (peri‑implant crestal bone loss [PCBL]) peri‑implant variables were recorded. Bacterial species including Porphyromonas gingivalis and Treponema denticola were evaluated from peri‑implant plaque biofilms. Levels of interleukin (IL)-1β and IL-6 were assessed after the collection of peri‑implant sulcular fluid. All the evaluations were carried out at baseline, 3- and 6-months. The significance level was set to p < 0.05. Results All clinical parameters significantly reduced within both treatment groups (P<0.05). Intra-group comparison indicates that there was statistically significant reduction in PD and suppuration for ICG-PDT group (P<0.05). There was a statistically significant difference in the BOP between ICG-PDT and PIMD groups at both follow-up periods (P<0.001). However, there was a significant difference for PD (P = 0.001), suppuration (P = 0.01), and PCBL (P = 0.04) on 6 months follow-up between ICG-PDT and PIMD groups, respectively. Only ICG-PDT showed a significant reduction in P. gingivalis and T. denticola on both 3 months and 6 months follow-up compared to baseline. PIMD showed a statistically significant reduction only on 3 months follow-up compared to baseline. This reduction was maintained for both the species when dental implants were treated with ICG-PDT. However, PIMD failed to maintain this reduction until 6 months. Only at 3 months assessment that both treatment groups showed statistically significant reduction in IL-1β and IL-6 with no significant difference between the groups. Both biomarkers failed to maintain the reduction in both groups and significantly increased levels for IL-1β was noted at 6 months follow up Conclusion Multiple application of indocyanine-green mediated photodynamic therapy resulted in improved clinical and microbial parameters among type 2 DM subjects in the treatment of peri‑implantitis. This clinical trial was registered in the ClinicalTrials.gov Protocol Registration and Results System with registration record number: NCT04833569., (Copyright © 2021. Published by Elsevier B.V.)

Background: Removal of dental plaque and local application of local chemical adjuncts, such as chlorhexidine (CHX), have been used to control and treat peri-implant disease. However, these methods can damage the surface properties of the implants or promote bacterial resistance. The application of ozone as an adjunctive treatment represents a new approach in the management of peri-implantitis. Thus, the purpose of this study was to evaluate the antimicrobial effect of ozonized physiological saline solution in different concentrations against oral biofilms developed on titanium surface., Methods: Single and multi-species biofilms of Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus oralis were formed on titanium specimens for 5 days in anaerobic conditions. Biofilms were treated with ozonized saline solution at different concentrations (25, 50, and 80 μg/NmL), for 30 seconds and 1 minute. CHX (0.12%) and saline solution (0.89% NaCl) were used as positive and negative controls, respectively. Bacterial viability was quantified by colony forming units (CFU mL -1 ), and biofilm images were acquired by confocal laser scanning microscopy (CLSM). Data were analyzed by parametric test (ANOVA) with Tukey post-hoc test (P < 0.05)., Results: Ozonized saline solution showed antibiofilm activity at a concentration of 80 μg/NmL for 30 seconds and 1 minute, reducing, mainly, Porphyromonas gingivalis viability, with 2.78 and 1.7 log 10 CFU mL -1 of reduction in both single and multi-species biofilms, respectively, when compared to the control (saline), whereas CHX reduced 1.4 and 1.2 log 10 CFU mL -1 ., Conclusion: Ozonized saline solution has antibiofilm activity, with better effect when applied for 1 minute at 80 μg/NmL, being a promising candidate therapy for the treatment of peri-implant diseases., (© 2020 American Academy of Periodontology.)

Background: Clinical benefits of local antibiotics as an adjunct to nonsurgical treatment of peri-implantitis have been widely reported, but most studies evaluated incipient peri-implantitis lesions, and showed incomplete treatment success rates., Purpose: To assess the clinical and microbiological outcomes of administering metronidazole in combination with minocycline as a local adjunct to the nonsurgical treatment of peri-implantitis., Materials and Methods: One hundred and eighteen subjects with peri-implantitis were recruited in a four-center, three-arm, and 12-week randomized controlled trial. Subjects were randomly assigned to receive one of the following treatments: (a) MM-mechanical debridement + metronidazole-minocycline ointment, (b) MC-mechanical debridement + minocycline ointment, (c) NST-mechanical debridement only., Results: Except for four subjects who was excluded during the trial, a total of 114 patients with 114 implants (one implant per each patient) finally completed the trial and were included in the analyses. Multivariate logistic regression analysis revealed that the treatment success rates (absence of bleeding or suppuration on probing, and sites showing pocket probing depth [PPD] ≥5 mm) on at 12 weeks were higher in MM-group patients (31.6%) and MC-group patients (20.5%) compared to NST-group patients (2.7%; p = 0.011 and 0.040, respectively). Subjects with deepest PPD ≥8 mm showed a significant difference in the PPD reduction between MM and MC groups at week 4 (p = 0.025) and week 12 (p = 0.047). Detection ratio of Tannerella forsythia was significantly lower for MM group than MC group (p = 0.038)., Conclusions: Additive use of either MM or MC results in significantly higher treatment success rates compared to sole mechanical debridement in nonsurgical treatment of peri-implantitis. Moreover, MM contributes to a significantly greater reduction in the PPD compared to MC in deep pockets (cris.nih.go.kr KCT0004557)., (© 2021 Wiley Periodicals LLC.)

Aim: The aim of this single-blind RCT was to evaluate the adjunctive clinical and microbiological effect of systemic amoxicillin (AMX) plus metronidazole (MTZ) to non-surgical treatment of peri-implantitis., Material and Methods: Patients (N = 62) with peri-implantitis were randomly assigned to receive full-mouth mechanical debridement and decontamination and use of chlorhexidine (control group) or combined with antibiotic therapy of AMX/MTZ (test group). Primary outcome was change in bleeding score from baseline (T 0 ) to 3-month follow-up (T 3 ). Secondary parameters were plaque, suppuration, PPD, CAL, bone level, microbiology, adverse events and need for additional surgery. Data were analysed with linear multiple regression analysis., Results: 57 patients with 122 implants completed 3-month follow-up. Both groups showed major clinical improvements at T 3 in both peri-implant and periodontal parameters. However, no significant differences were observed between both groups for any of the primary or secondary parameters., Conclusions: Systemic antibiotic therapy of AMX/MTZ does not improve clinical and microbiological outcomes of non-surgical peri-implantitis treatment and should not be routinely recommended. Although complete disease resolution may be difficult to achieve, meticulously performed full-mouth non-surgical treatment, achieving a high level of daily oral hygiene and healthy periodontal tissues, can significantly improve the starting position of the subsequent (surgical) peri-implantitis treatment phase., (© 2021 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Clinical efficacy of antimicrobial photodynamic therapy (aPDT) as compared to antibiotics in periodontitis and peri-implantitis has been tested in several clinical trials. Yet controversial results were reported. The aim of the present study was to answer the question: "Will adjunctive antimicrobial photodynamic therapy be more effective than antibiotics agent in the treatment of periodontitis and peri-implantitis?"., Methods: Publications compared outcomes between aPDT and antibiotics in adult patients with periodontitis or peri-implantitis, containing more than 3-month follow-up duration, were involved in the systematic review and meta-analysis. PubMed, EMBASE and Cochrane Central were searched until December of 2020. Clinical parameters including pocket probing depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were evaluated. The risk of bias was assessed by Cochrane Collaboration Tool. Weighted mean differences (WMD), 95 % confidence interval(CI) and heterogeneity were estimated by Review Manager software., Results: 10 trials in periodontitis and 5 trials in peri-implantitis were included. Meta-analysis outcomes revealed equal clinical evidence for aPDT and antibiotics in periodontitis and peri-implantitis. In addition, aPDT significantly reduced the red complex in both diseases. However, owing to the heterogeneity of protocols in articles and the limited number of studies, the comparative conclusion remained unconfirmed., Conclusion: aPDT can be considered as an alternative to antibiotics in the treatment of peri-implantitis and periodontitis. Given that high heterogeneity in outcome was found in this review, future long-term clinical trials with standard aPDT and antibiotic treatment should be tested to arrive at a firm conclusion., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As dental implants have become one of the main treatment options for patients with tooth loss, the number of patients with peri-implant diseases has increased. Similar to periodontal diseases, peri-implant diseases have been associated with dental plaque formation on implants. Unconventional approaches have been reported to remove plaque from infected implants, but none of these methods can completely and permanently solve the problem of bacterial invasion. Fortunately, the constant development of antibacterial implant materials is a promising solution to this situation. In this review, the development and study of different antibacterial strategies for dental implant materials for the prevention of peri-implantitis are summarized. We hope that by highlighting the advantages and limitations of these antimicrobial strategies, we can assist in the continued development of oral implant materials.

The aim of this systematic review and meta-analysis was to determine the efficacy of chlorhexidine (CHX) as an adjunctive therapy to mechanical debridement in the treatment of peri-implant diseases. Five databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trails, Web of Science, and ClinicalTrials.gov) were searched. Randomized controlled trials (RCTs) comparing mechanical debridement combined with CHX to mechanical debridement alone for patients with peri-implant disease were identified. The trial investigators evaluated factors indicating inflammatory levels, including bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL). Six RCTs with 207 patients were ultimately included in this review. Low- to moderate-quality evidence demonstrated that the adjunctive CHX therapy had no significant effect on BOP reduction within 1 month (mean difference [MD], 0.10; 95% confidence interval [CI], -0.06 to 0.25), 3-4 months (MD, 0.06; 95% CI, -0.03 to 0.15), and 6-8 months (MD, 0.06; 95% CI, -0.03 to 0.14) of follow-up. Significant differences in PD reduction and CAL gain were also not found. Although 1 subgroup analysis revealed a significant result (MD, 009; 95% CI, 0.01-0.18) for the use of CHX solution, this could be interpreted as clinically slight. Based on available evidence, adding CHX to mechanical debridement, compared with mechanical debridement alone, did not significantly enhance the clinical results. Therefore, clinicians should consider the negligible effect of adjunctive CHX.

Objective: To investigate the role of implant surface debridement alone and in conjunction with systemic antibiotics on the clinical and microbiological variables of periimplantitis., Materials and Methods: Data of forty-six patients with at least one dental implant having bleeding-on-probing (BoP), probing pocket depth (PPD) of more than 5 mm, and radiographic bone loss of more than 3 mm were retrieved from clinical records. Data was recorded for dental implant with the deepest PPD, BoP, and bone loss from each patient. "Group-A" received implant surface debridement alone, while "group-B" additionally received systemic antibiotics. Clinical and microbiological data of patients were compared before and after the treatment., Results: At the implant level, a significant reduction of PPD, mucosal recession (MR), and BoP was achieved for all patients. Group B achieved significant improvement in MR and BoP compared to group A at implant level. PPD, MR, and plaque scores showed improvement at implant site level. At 3 months recall visit, 44% of group A and 52% of group B implants required surgical treatment. The presence and proportions of studied bacteria of both groups did not differ significantly at the recall visit when compared to the initial visit. However, P. intermedia and P. micros showed a significant reduction in group A at the recall visit., Conclusions: Implant surface debridement improved the clinical parameters of periimplantitis. In addition, adjunctive use of systemic antibiotics increased mucosal recession and improved bleeding on probing in periimplantitis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Muhammad Irshad et al.)

During the last decade, photodynamic therapy (PDT) has been extensively investigated for the treatment of periodontal and peri-implant infections. Nonetheless, contradicting clinical and microbiological outcomes and only results on a short-term basis have been reported so far, thus making it difficult to conclude on clinically relevant recommendations for the use of PDT. Therefore, the aim of this narrative review is to provide an overview of the current evidence from randomized controlled clinical trials (RCTs) evaluating the potential clinical and/or microbiological benefit for the use of PDT in non-surgical periodontal and peri-implant therapy, and to draw clinically relevant conclusions on the use of PDT in periodontal practice. Based on the available evidence from RCTs and recent meta-analyses, we can conclude the following: in patients with mild to moderate periodontitis, the combination of scaling and root planing (SRP) and PDT may result in significantly higher clinical improvements (bleeding on probing and probing depth reduction, clinical attachment gain) compared to SRP alone in the non-surgical treatment of periodontitis; in patients with stage III and IV grade C periodontitis (previously known as AgP) the use of PDT provides clinical improvements, although PDT cannot so far be recommended as a replacement for systemic antibiotics (i.e., amoxicillin and metronidazole); PDT may be indicated as a valuable tool for treating moderate residual periodontal pockets during maintenance therapy; limited evidence on the use of PDT in medically compromised patients (i.e., diabetes mellitus, oral lichen planus) indicates that PDT may represent a possible alternative to other more invasive medication/treatment procedures; limited evidence suggests that PDT may represent a valuable tool in attaining inflammation reduction on a short-term basis in peri-implant diseases (i.e., peri-implantitis, peri-implant mucositis)., (© 2021 S. Karger AG, Basel.)

Objective: The aim of this study was to evaluate the effectiveness of hyaluronic acid and chlorhexidine mouthwash in the treatment of peri-implant mucositis., Material and Methods: Clinical and microbiological studies were conducted before and 14 days, 1, 3 and 6 months after the periodontal treatment in 46 patients (144 implants with fixed dentures) with peri-implant mucositis. The patients were divided into 3 groups: test, comparison and control. Basic periodontal therapy in all groups included professional cleaning and individual oral hygiene training. Test group (15 patients) received basic periodontal therapy plus 0.20% chlorhexidine with hyaluronic acid mouthwash, the comparison group (15 patients) - basic periodontal therapy +0.05% chlorhexidine mouthwash. In control group (16 patients), treatment was limited to basic periodontal therapy only., Results: At the initial stages of observations, there was a statistically significant improvement in the clinical indices in all treatment groups ( p <0.001). The use of 0.20% chlorhexidine with hyaluronic acid mouthwash revealed a higher quality of treatment. After 6 months of observation, the clinical features in patients of the control group was almost similar to the state before treatment. The patients of the test group had a more pronounced elimination of facultative and periodontal pathogens in comparison with other groups., Conclusion: The use of 0.20% chlorhexidine with hyaluronic acid containing mouthwash allows the clinician to achieve a better results in the treatment of peri-implant mucositis. The evaluation the oral microflora in patients with peri-implant mucositis can be used as a prognostic criterion for the outcomes of rehabilitation.

Background: Peri-implantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of peri-implantitis. This study compared the safety and efficacy of chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive treatment to subgingival debridement in patients afflicted with peri-implantitis., Methods: A multicenter, randomized, single-blind, two-arm, parallel Phase-3 study was conducted. Peri-implantitis patients with implant pocket depths (IPD) of 5-8 mm underwent subgingival implant surface debridement followed by repeated bi-weekly supragingival plaque removal and chlorhexidine chips application (ChxC group) for 12 weeks, or similar therapy but without application of ChxC (control group). All patients were followed for 24 weeks. Plaque and gingival indices were measured at every visit whereas IPD, recession, and bleeding on probing were assessed at 8, 12, 16, 24 week., Results: A total of 290 patients were included: 146 in the ChxC group and 144 in the control. At 24 weeks, a significant reduction in IPD (P = 0.01) was measured in the ChxC group (1.76 ± 1.13 mm) compared with the control group (1.54 ± 1.13 mm). IPD reduction of ≥2 mm was found in 59% and 47.2% of the implants in the ChxC and control groups, respectively (P = 0.03). Changes in gingival recession (0.29 ± 0.68 mm versus 0.15 ± 0.55 mm, P = 0.015) and relative attachment gain (1.47 ± 1.32 mm and 1.39 ± 1.27 mm, P = 0.0017) were significantly larger in the ChxC group. Patients in the ChxC group that were < 65 years exhibited significantly better responses (P < 0.02); likewise, non-smokers had similarly better response (P < 0.02). Both protocols were well tolerated, and no severe treatment-related adverse events were recorded throughout the study., Conclusions: Patients with peri-implantitis that were treated with an intensive treatment protocol of bi-weekly supragingival plaque removal and local application of chlorhexidine chips had greater mean IPD reduction and greater percentile of sites with IPD reduction of ≥2 mm as compared with bi-weekly supra-gingival plaque removal., (© 2020 American Academy of Periodontology.)

Aim: The current clinical trial aimed to assess the effectiveness of adjunctive photodynamic therapy (aPDT) and adjunctive antibiotic gel therapy (aAGT) to treat peri-implantitis among patients with type 2 diabetes mellitus (T2DM)., Methods: Selected T2DM participants with peri-implantitis were distributed into 3 groups: Group-1: received a single session of adjunctive (aPDT); Group-2: received a single session of adjunctive (aAGT) (metronidazole 400 mg and amoxicillin 500 mg); and Group-3: received MD alone. Clinical (probing depth [PD], bleeding on probing [BOP], and plaque scores [PS]) and radiographic (crestal bone loss [CBL]) peri-implant variables were recorded. Levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were assessed after the collection of peri-implant sulcular fluid (PISF). All the evaluations were carried out at baseline, 3- and 6-months. The significance level was set to p < 0.05., Results: At 3-and 6-months of follow-up, all the three groups showed significant alleviation in PS (p < 0.05), BOP (p < 0.05), and PD (p < 0.05) when compared with the baseline. At baseline, no significant variation was observed in all clinical and radiographic peri-implant parameters among all three research groups. At 3-months follow-up, a considerable alleviation of in PS, BOP, PD, and CBL was noticeable in group-1 patients when compared with the baseline. At 6-months follow-up, a comparable difference was observed in BOP, PD, and CBL between group-1 and group-2. At baseline, no significant variation was observed in the PISF levels of IL-6 and TNF-α among all three research groups. At 3- and 6-months follow-up, a considerable alleviation of TNF-α and IL-6 levels was observed in group-1 and group-2 patients, respectively, when compared with the baseline., Conclusion: The application of aPDT demonstrated improved clinical, radiographic, and immunological peri-implant parameters for the treatment of peri-implantitis among T2DM patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Objective: Macrophages' cytokine expression and polarization play a substantial role in the host's "destructive" inflammatory response to periodontal and peri-implant pathogens. This study aimed to evaluate cell viability, anti-inflammatory activity, and macrophage polarization properties of different cranberry concentrates., Methods: THP-1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB-G cell line), osteosarcoma-derived osteoblasts (SAOS-2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti-inflammatory analysis, induced macrophages exposed to cranberry concentrates (A-type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)-8, IL-1 ß, IL-6, and IL-10 expression of LPS-stimulated macrophages, and macrophage polarization markers were evaluated through determination of live-cell protease activity, enzyme-linked immunosorbent assay, and immunofluorescence staining semi-quantification., Results: Cranberry concentrates (A-type PACs) did not reduce HGF, SAOS-2, and macrophage viability after 24 hours of exposure. Pro-inflammatory cytokine expression (ie IL-8 and IL-6) was downregulated in LPS-stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti-inflammatory IL-10 expression was significantly upregulated in LPS-stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS-stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS-stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours., Conclusion: Cranberry-derived proanthocyanidins may have the potential to act as an anti-inflammatory component in the therapy of periodontal and peri-implant diseases., (© 2020 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Osteogenic differentiation of dental pulp stem cells (DPSCs) is considered as a promising strategy in posterior maxilla tooth implantation. Information on the function and mechanisms of long non-coding RNAs (lncRNAs) in osteogenic differentiation of DPSCs is growing, however, the mechanism of LINC00968 and miR-3658 in regulating osteogenic differentiation of DPSCs still needs to be explored. In this study, the LINC00968 and miR-3658 expression level was upregulated and downregulated in DPSCs and peri-implantitis DPSCs (pDPSCs) treated with bone morphogenic protein (BMP)2, respectively. Moreover, the effects of LINC00968 and miR-3658 on BMP2-induced osteogenic differentiation of DPSCs in vitro using Alizarin Red S staining, alkaline phosphatase (ALP) activity, quantitative real time PCR and Western blot assays showed that overexpression of LINC00968 significantly promoted mineralized bone matrix, alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osterix (OSX) expression levels for osteogenic differentiation of DPSCs and pDPSCs; and overexpression of miR-3658 showed an opposite result that inhibited osteogenic differentiation of DPSCs and pDPSCs. Luciferase reporter assay showed that luciferase activities of LINC00968-WT reporter and RUNX2-WT reporter were strongly suppressed by miR-3658 overexpression. In addition, the miR-3658 upregulation interfered ectopic bone formation in vivo stimulated by LINC00968. In general, we had identified a novel molecular pathway involving LINC00968/miR-3658/RUNX2 during DPSCs and pDPSCs differentiation into osteoblasts, which might facilitate bone anabolism., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Obesity appears to govern peri-implant hard and soft tissue health. We hypothesized that adjunctive photodynamic therapy (aPDT), improves clinical peri-implant perimeters and alleviates peri-implant crevicular fluid (PICF) levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and high sensitivity C-reactive protein (hsCRP) in obese with moderate peri-implantitis. The current clinic-laboratory study aimed to determine whether obesity influences the outcomes of aPDT in patients with moderate peri-implantitis., Methods: A total of 49 patients (24 obese and 25 non-obese) with moderate periodontitis receiving aPDT were included. Clinical characteristics including peri-implant probing depth (PIPD), peri-implant bleeding on probing (PIBOP), and peri-implant plaque index (PIPI) were measured. PICF levels of TNF-a, IL-6 and hsCRP were assessed using enzyme-linked immunosorbent assay (ELISA). Both clinical and cytokine assessments were performed at baseline, three months and six months, respectively. Intra-group comparisons of changes in clinical parameters pre and post PDT was performed using Friedman test. Comparison of changes of TNF-a, IL-6 and hsCRP levels within group was performed using Kruskal-Wallis test., Results: When compared with the baseline, a considerable reduction in PIPI, PIBOP and PIPD was observed in obese as well as non-obese patients at three- and six-months follow-up. At three months follow-up, a statistically significant difference was observed in PIPI (p < 0.05), PIBOP (p < 0.05) and PIPD (p < 0.05) among obese and non-obese individuals. Additionally, when compared with the baseline, a statistically significant difference was noticed in PICF volume (p < 0.05) and levels of TNF-α (p < 0.05) and IL-6 (p < 0.05) in non-obese as well as obese at three- and six-months follow-up., Conclusion: With the application of aPDT, considerable improvement was observed in peri-implant inflammatory parameters among obese and non-obese patients with moderate peri-implantitis. Obesity did not appear to influence aPDT outcome in patients with moderate peri-implantitis., (Copyright © 2020. Published by Elsevier B.V.)

Background: There is no reliable treatment procedure for peri-implant disease, despite the rise in its incidence. This study sought to evaluate the short-term safety and efficacy of antimicrobial photodynamic therapy (a-PDT) on peri-implantitis by assessing the volume of pus discharge after a-PDT., Methods: Patients with pus discharge from a peri-implant pocket were recruited from December 1st, 2019 to April 30th, 2020. The enrolled implants were randomly assigned to one of two groups, the irrigation and a-PDT groups. Their peri-implant pocket was irrigated with normal saline in the irrigation group, and a saline irrigation and subsequent a-PDT with toluidine blue (TB) was performed in the a-PDT group. The safety and efficacy of a-PDT were assessed 7 days after treatment., Results: Twenty-five implants in 21 patients (irrigation group; 13 implants, a-PDT group; 12 implants) were registered. No complication was observed after a-PDT. Pus discharge was decreased in 7 of 12 implants (58.3 %) in the a-PDT group, and in 2 of 13 implants (15.4 %) in the irrigation group. According to Fisher's exact test, a-PDT resulted in a statistically significant decrease in pus discharge compared to irrigation alone (p = 0.0414)., Conclusions: a-PDT was confirmed to be a safe treatment for peri-implantitis, and the short-term efficacy of a-PDT with TB on peri-implantitis was clarified. Nevertheless, its efficacy remains restricted, and a new combination therapy of a-PDT and decontamination procedures is expected to be developed in future., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: What impact does tobacco smoking have on photodynamic therapy (PDT) outcome is still unknown. The aim of the present clinical trial was to evaluate the clinical, radiographic, and biological bone markers after provision of PDT in cigarette, e-cigarette, and never-smokers with peri-implantitis (PI) at 6 months post treatment., Materials and Methods: Twenty-five healthy patients with PI were divided into three groups: Group I: cigarette smokers; Group II: e-cigarettes users; Group III: never-smokers. Full-mouth mechanical debridement with adjunctive methylene blue-mediated PDT was performed. Clinical recordings included peri-implant plaque index (Pi), bleeding on probing (BOP) and probing depth (PD). Peri-implant sulcular fluid was collected for the assessment of biological bone biomarkers including receptor activator of nuclear factor-ligand (RANK-L) and osteoprotegrin (OPG). All assessments were performed at baseline, 3 months and 6 months. P-value of <0.05 was considered significant., Results: BOP in Group II and III significantly reduced at 3 months (p < 0.05). Group I showed significant reduction only at 6 months (p < 0.05). Mean PD showed no statistically significant difference between the groups at any time-point. Inter-group comparison showed Group III demonstrating statistically significantly reduced mean RANK-L levels at both 3 and 6 months (p < 0.05). A slight increase in the OPG levels were observed at 3 months and followed by a slight decrease at 6 months for all the study groups when compared with baseline values, however, these values did not show statistical significance (p > 0.05)., Conclusion: Adjunctive PDT helped in reducing the clinical peri-implant inflammation. However, no significant change was observed for biological bone biomarkers among tobacco smokers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: The aim of the present study was to compare the effectiveness of mechanical debridement (MD) with and without adjunct antimicrobial photodynamic therapy (aPDT) for treating peri-implant mucositis among prediabetic cigarette-smokers and non-smokers., Methods: Prediabetic and non-diabetic smokers and non-smokers with peri-implant mucositis were included. Patients with peri-implant mucositis were divided into 4 groups as follows: Group-1: Prediabetic smokers with peri-implant mucositis; Group-2: Prediabetic non-smokers with peri-implant mucositis; Group-3: Systemically-healthy smokers with peri-implant mucositis; and Group-4: Systemically-healthy non-smokers with peri-implant mucositis. Hemoglobin A1c levels were measured in all groups prior to MD with adjunct aPDT. Peri-implant plaque index (PI), bleeding on probing (BOP) and probing depth (PD) were assessed at baseline and at 4- and 12-weeks of follow-up. Sample-size estimation was done and data normality was assessed. Group-comparisons were performed. and P < 0.01 was selected as an indicator of statistical significance., Results: Fifteen, 15, 15 and 15 individuals were included in groups 1, 2, 3 and 4, respectively. At baseline, peri-implant PI, BOP and PD were comparable in all groups. In prediabetic smokers and non-smokers, there was no significant difference in peri-implant PI, BOP and PD at 4- and 12-weeks' follow-up. Among non-diabetic smokers and non-smokes MD with adjunct PDT significant reduced PI (P < 0.01) and PD (P < 0.01) at 4- and 12-weeks' follow-up., Conclusion: The outcomes of MD with adjunct aPDT for the treatment of peri-implant mucositis are compromised in smokers and non-smokers with prediabetes. In non-diabetic smokers and non-smokers, MD with aPDT is effective for treating peri-implant mucositis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: The study's aim was to assess the clinical outcome 6 and 12 months after a nonsurgical treatment of peri-implantitis per se or in conjunction with a combination of local antiseptic and anti-inflammatory treatment., Materials and Methods: Included were 69 patients with periodontitis, with 106 implants, diagnosed with peri-implantitis. Peri-implantitis was defined as radiographic bone loss ≥3 mm, probing depth (PD) ≥ 6 mm, with bleeding on probing. Group M peri-implantitis was treated with ultrasonic debridement and soft tissue curettage. Group P had additional implant surface treatment with rotatory hand piece composed of chitosan bristle, soft tissue curettage combined with application of 0.95% hypochlorite and 1 mg minocycline HCl., Results: After 6 months, both groups demonstrated significant reduction of mean plaque index, PD, and clinical attachment level (0.71 ± 0.57, 0.81 ± 0.55; 4.77 ± 0.73 mm, 4.42 ± 0.5 mm; 5.03 ± 0.86 mm, 5.13 ± 0.73 mm; respectively) and bleeding on probing. After 6 and 12 months, group P showed significantly better PD results compared to group M. The bleeding was significantly less in group P after 12 months (15.3% ± 6.2, 25.1% ± 8.2, respectively)., Conclusions: Adjunctive treatment with local antiseptic and anti-inflammatories during mechanical phase was positively associated with inflammation reduction and connective tissue reattachment., (© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Purpose: To study the effect of chlorhexidine combined with mechanical debridement on peri-implant inflammation and the influence on SF-36 score of patients., Methods: One hundred patients with peri-implantitis admitted to Zhejiang Provincial People's Hospital from January 2015 to January 2019 were selected and randomly divided into control group and combined group with 50 cases in each group according to random number table method.Patients in both groups were treated with mechanical debridement, and patients in the combined group were gargled with chlorhexidine gargle apart from mechanical debridement. Plaque biofilm average activity and modified plaque index (mPLI), bleeding on probing (BOP), modified sulcus bleeding index (mSBI), probing the depth (PPD), clinical attachment level(AL) were measured before and after treatment. Sf-36 scale and VAS visual pain score were used to evaluate the quality of life and pain degree of patients, and the therapeutic effect and incidence of complications were assessed. The data were analyzed with SPSS 20.0 software package., Results: There was no significant difference in average activity, mPLI, mSBI, AL, PPD, BOP, VAS and SF-36 scores between the two groups before treatment(P>0.05); after treatment, the average activity, mPLI, mSBI, AL, PPD, BOP and VAS scores of plaque biofilm in the combined group were significantly lower than those of the control group, and the total effective rate of SF-36 score was significantly higher than that of the control group. The total effective rate of the combined group was significantly higher than that of the control group(P<0.05). The incidence of complications in the combined group was significantly lower than that in the control group(P<0.05)., Conclusions: Chlorhexidine combined with mechanical debridement is an effective treatment of peri-implantitis, which can effectively inhibit plaque biofilm activity and plaque formation, alleviate pain and improve the quality of life of patients.

Dental implant surgery is a routine treatment in clinical dentistry. However, implant surgery is associated with an increased risk of bacterially induced peri-implantitis and the production of reactive oxygen species (ROS), with no established treatment. We recently designed a new redox injectable gel (RIG) containing nitroxide radicals for the treatment of peri-implantitis. Here, we investigated the antioxidative effect of RIG as a preventive therapy for ROS-associated peri-implantitis in a rat model of alveolar bone resorption and in vitro. In each rat, the maxillary first molar tooth was replaced with a screw-type implant, and rats were assigned to one of four groups: an implant alone, an implant with infection, implant with infection and treatment with nRIG (a non-nitroxide radical-containing injectable hydrogel) or RIG. We confirmed the long-term retention of RIG in the peri-implant region and found that RIG significantly protected the alveolar bone volume and decreased lipid peroxidation. In culture, we found that RIG restored osteoblast proliferation and differentiation in the presence of hydrogen peroxide (H 2 O 2 )-induced oxidative stress. Moreover, using a malondialdehyde assay of lipid peroxidation, we found that RIG suppressed oxidative stress in H 2 O 2 -treated rat osteoblasts. Overall, RIG is anticipated as a prophylactic treatment for peri-implantitis and may help preserve oral function. Statement of Significance 1. Implant surgery is associated with an increased risk of bacterially induced peri-implantitis and the production of reactive oxygen species (ROS). We designed a novel redox injectable gel (RIG) containing nitroxide radicals for the treatment of peri-implantitis. In this study, we investigated the antioxidative effect of RIG as a preventive therapy for ROS-associated peri-implantitis in a rat model and in vitro. 2. We showed that treatment with RIG reduces oxidative damage in a rat peri-implantitis model, protecting against bone resorption and a loss of bone density. We showed that RIG inhibits H 2 O 2 -mediated decreases in proliferation, osteoblast differentiation, and mineralization, and also against lipid peroxidation in vitro. Our results indicate that RIG has an antioxidative effect of peri-implantitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Aim: To study effect of delmopinol hydrochloride (DEL) in comparison with chlorhexidine digluconate (CHX) and a placebo (PLA) in addition to non-surgical mechanical debridement in patients with peri-implant mucositis., Materials and Methods: Eighty-nine patients with at least one implant diagnosed with peri-implant mucositis were randomly assigned to one of three study groups (DEL, CHX and PLA). Professional non-surgical mechanical debridement was performed at baseline. Mouth rinsing was carried out by the patients twice a day in addition to their regular oral hygiene practices. Assessments of efficacy were performed for the primary outcome - Implant bleeding on probing (IBOP%) and secondary outcomes - modified Bleeding Index (mBI) and modified Plaque Index (mPI) at 1 and 3 months., Results: At 3 months, there was statistically significant reduction in IBOP% and mBI within the study groups compared to baseline. However, there was no statistically significant difference between the study groups at 3 months follow-up. Moreover, there was a statistically significant difference according to mPI at 1 month between the chlorhexidine and placebo group (p = .004)., Conclusions: This study confirms that mechanical debridement combined with oral hygiene instruction is effective in treatment of peri-implant mucositis. The clinical effects between groups were comparable., (© 2020 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objectives: The aim of this study was to conduct a systematic review and meta-analysis on the efficacy of growth factors (GF) on clinical outcomes after treatment (surgical/non-surgical) of peri-implant diseases (peri-implant mucositis and peri-implantitis)., Materials and Methods: A protocol was developed to answer the following focused question: Is there any difference for the use of GF for treatment of peri-implant diseases versus comparative GF treatment or without GF? Electronic database and manual searches were independently conducted to identify randomized controlled trials (RCTs). Publications were selected based on eligibility criteria and then assessed for risk-of-bias using the Cochrane Handbook. The primary outcome was probing depth (PD) and bleeding on probing (BOP) reduction along with changes in vertical defect depth (VDD). Changes in clinical attachment level, gingival recession, and plaque index, among others, were studied as secondary outcomes. Based on primary outcomes, random-effects meta-analysis was conducted., Results: A total of five RCTs were included. GF enhance the reduction of PD (standardized mean difference (SMD) = - 1.28; 95% confidence interval (CI) - 1.75, - 0.79; p = < 0.0001) and BOP (SMD = - 1.23; 95% CI - 1.70, - 0.76; p = < 0.0001) in the management of peri-implant mucositis. For the treatment of peri-implantitis, the use of GF yielded to significantly greater improvement in VDD (SMD = 0.68; 95% CI 0.22, 1.14; p = 0.004); however, there were no significant differences in terms of PD (SMD = 0.08; 95% CI - 1.08, 1.26; p = 0.887) and BOP (SMD = 0.211; 95% CI - 0.20, 0.63; p = 0.317). The overall risk of bias of the included studies was low to unclear., Conclusion: The results of the present systematic review suggest that the addition of GF might enhance the outcomes in the treatment of peri-implant mucositis. However, there is a lack of evidence for supporting additional benefit of GF managing peri-implantitis., Clinical Relevance: Within the limitations of the current systematic review and based on the meta-analyses, (1) the addition of GF for the treatment peri-implant mucositis might be associated with better outcomes in terms of PD and BOP, and (2) an additional benefit of GF for the treatment peri-implantitis could not be determined on the basis of the selected evidence.

Background: Dental implant failures still occur because of peri-implant diseases such as peri-implantitis. The objective of this study was to treat peri-implantitis in beagle dogs by fabricating minocycline hydrochloride (MH)-loaded graphene oxide (GO) films on implant abutment surfaces., Methods: Beagle dogs with silk ligature were used to establish the peri-implantitis model. Modified sulcus bleeding index, peri-implant probing pocket depth, radiographic evaluation, micro-CT tomography analysis, and histological evaluation were determined to evaluate the therapeutic effect of MH-loaded GO films on abutment surfaces for peri-implantitis., Results: Radiographic and micro-CT analysis showed that lots of marginal bone loss could be found on Ti and MH/Ti groups, especially for Ti group. Little bone less could be seen on GO/Ti group while bone less on MH/GO/Ti group was negligible. Results of the histological analysis presented that lots of neutrophils could be found on Ti and MH/Ti groups. However, almost none of the neutrophils could be observed on GO/Ti and MH/GO/Ti while lots of osteocytes could be found., Conclusion: MH-loaded GO films on implant abutment surfaces could prevent the further development of peri-implantitis and exhibit good therapeutic effect for peri-implantitis in beagle dogs., (© 2019 American Academy of Periodontology.)

Background: The aim of our study was to evaluate the effects of a hyaluronic acid (HA) gel at 45 days on the microbiome of implants with peri-implantitis with at least 1 year of loading., Methods: A randomized controlled trial was conducted in peri-implantitis patients. Swabs containing the samples were collected both at baseline and after 45 days of treatment. 16S rRNA sequencing techniques were used to investigate the effect of HA gel on the subgingival microbiome., Results: One hundred and eight samples of 54 patients were analyzed at baseline and after follow-up at 45 days. Three strata with different microbial composition were obtained in the samples at baseline, representing three main microbial consortia associated with peri-implantitis. Stratum 1 did not show any difference for any variable after treatment with HA, whereas in stratum 2, Streptococcus, Veillonella, Rothia, and Granulicatella did decrease (P < 0.05). Similarly, Prevotella and Campylobacter (P < 0.05) decreased in stratum 3 after treatment with HA. Microbial diversity was found to be decreased in stratum 3 (P < 0.05) after treatment with HA compared with the control group, in which an increase was found (P < 0.05)., Conclusions: HA reduced the relative abundance of peri-implantitis-related microorganisms, especially the early colonizing bacteria, suggesting a specific action during the first stages in the development of the disease. HA did not alter relative abundances of non-oral genera. The use of HA in advanced stages of peri-implantitis resulted in a decrease in microbial alpha diversity, suggesting a protective action of the peri-implant site against bacteria colonization., (© 2019 American Academy of Periodontology.)

Aim: The aim of the present clinical trial was to evaluate the efficacy of photodynamic therapy (PDT) as an adjunct to mechanical debridement (MD) in the treatment of severe peri-implantitis (PI) with abscess., Materials and Methods: Selected individuals with severe PI were divided into two groups: Group A: received methylene blue mediated (PDT) using diode laser as an adjunct to MD, whereas, Group B received thrice daily application of 500 mg amoxicillin and 400 mg metronidazole with adjunctive MD. Peri-implant plaque scores (PS), probing depth (PD), bleeding on probing (BOP) and clinical attachment loss (CAL) were reported. Microbial counts of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia were analyzed using polymerase chain reaction. The assessment of pain was done with the help of numeric pain rating scale (NPRS). All assessments were done at baseline and repeated at 6 and 12 months, respectively., Results: A total of 40 individuals completed the clinical trial. Both Group A and Group B comprised of 20 patients respectively. A significant improvement was observed in BOP in Group A at 12 months compared to Group B. No statistically significant changes were seen for NPRS scores between both groups (p > 0.05). Statistically significant differences were observed in values for P. gingivalis, T. denticola and T. forsythia at 6 months follow-up period in comparison to baseline for both Group A and Group B (p < 0.05). Whereas, the values observed at 6 months follow-up period for Porphyromonas gingivalis also reported a statistically significant difference in between the groups (p < 0.05)., Conclusion: PDT was equally effective in reducing severe peri-implant symptoms compared to antimicrobial therapy as an adjunct to mechanical debridement., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effects of adjunctive delivery of a sodium hypochlorite gel in the treatment of peri-implant mucositis (PM)., Materials and Methods: Forty-six subjects with 68 implants diagnosed with PM were randomly assigned to two treatment groups. Prior to mechanical debridement, a sodium hypochlorite gel was delivered to the implants of the test group while implants of the control group received a placebo gel. Application of both test and placebo gels was repeated 5 times at baseline. The primary outcome variable was the change in pocket probing depth (PPD) between baseline and 6 months., Results: After 6 months, the mean PPD decreased statistically significantly from 3.93 ± 1.09 mm to 3.04 ± 0.46 mm in the test (p = 0.0001) and from 3.68 ± 0.85 mm to 3.07 ± 0.58 mm in the control (p = 0.0001) group, respectively. No statistically significant difference (p = 0.53) was observed with respect to PPD changes from baseline to 6 months between test (0.88 ± 1.04 mm) and control group (0.61 ± 0.75 mm), respectively. The number of implants with bleeding on probing (BoP) decreased statistically significantly from 33 to 18 in the test group (p = 0.0001) and from 34 to 23 in the control group (p = 0.0001) after 6 months., Conclusions: In conclusion and within the limits of the present study, changes in PPD from baseline to 6 months were not statistically significantly different between groups. Complete resolution of mucosal inflammation was not achieved with either of the therapies., Clinical Relevance: The present outcomes have showed that a complete resolution of peri-implant mucositis is not possible to obtain by means mechanical debridement with or without a sodium hypochlorite gel application.

Aim: The aim of this study was designed to assess the peri-implant oral hygiene parameters, clinical, radiographic, host-derived immune biomarkers and microbiological levels after photochemotherapy (PCT) and local antibiotic therapy (LAT) in peri-implantitis lesions among cigarette smokers., Materials and Methods: Fifty current cigarette smokers with peri-implantitis were divided into two groups: PCT and LAT. Test implants received PCT that consisted of toluidine blue photosensitizer and application of 660 nm diode laser with a total of 100 mW power and 124.3 W/cm 2 energy using continuous mode of irrigation for 60 s. Control implants received one-unit subgingival application of metronidazole gel in viscous consistency. Clinical measurements included the assessment of plaque scores (PS), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL). Intraoral standardized digital peri-apical radiographs were taken at baseline and at 12 months. Interleukin (IL)-1β and matrix metalloproteinase (MMP)-1 in the PICF were determined using the manufacturers guide from one-step enzyme-linked immunosorbent assay. Real-time polymerase chain reaction (PCR) for Parvimonas micra, Porphyromonas gingivalis and Tannerella forsythia was performed and counts evaluated at baseline, 3, 6 and 12-months., Results: Plaque scores reduced in both groups (p < 0.05). Mean BOP percentage significantly increased in both the groups at 1-month follow-up compared to baseline. Following this period, BOP showed reduction from 1-month to consecutive follow-up periods. The PD significantly reduced in both the groups with no statistically significant difference when compared between PCT and LAT groups at follow-up (p > 0.05). CAL did not change over the period and between both groups (p > 0.05). The differences from baseline to 12 months and between the groups for mesial and distal crestal bone levels did not show any statistical significance (p > 0.05). The levels of IL-1β significantly dropped from baseline to 12 months in the LAT group (p < 0.05). However, for PCT groups, the levels of IL-1β significantly reduced only at 12-month visit follow-up (p < 0.05). MMP-1 showed statistically significant reduction at 9 and 12-months compared with baseline for LAT group. Both P. gingivalis and T. forsythia showed statistically significant reduction in both the groups when values were compared from baseline to 3-, 6- and 12-months follow-up (p < 0.05). However, these differences were not significant when compared between the groups (p > 0.05)., Conclusion: Both PCT and LAT showed equal efficacies in improving clinical, host-derived immune biomarkers and microbiological parameters in peri-implant infection in cigarette smokers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previous studies report periodontitis and peri-implantitis being able to induce systemic low-grade inflammation, which is known to be associated with increased risk for some systemic medical disease such as cardiovascular disease. In this regard, recent studies have shown that host modulation therapy (HMT) together with traditional mechanical and surgical treatment not only cease the progression of periodontitis but also reduce the systemic collagenolytic biomarkers in both oral fluids and circulation. This suggests that the corresponding adjunctive HMT-medication could be effective in the prevention and treatment of dental peri-implantitis, as well. Furthermore, low-cost, safe, and practical oral fluid active matrix metalloproteinase-8 (aMMP-8) lateral-flow immunotests have been proposed as point-of-care/chair-side diagnostic tools to detect peri-implantitis and periodontitis, and to monitor their effective resolutions, while using various therapeutic strategies, including host modulation. This study reports the potential benefits of HMT-medication in the prevention and treatment of dental peri-implantitis among five patients (four of five were current/ex-smokers). In addition, the aMMP-8 point-of-care test diagnosed 20 peri-implantitis and 20 healthy controls correctly. In conclusion, this study and previous studies support the potential effectiveness of HMT-medication(s) and point-of-care/chair-side technologies in the treatment and diagnostics/monitoring of peri-implantitis. However, more studies are needed to further confirm this.

Antibiotic resistance is a major public health problem worldwide and the finding of alternative methods for eliminating bacteria is one of the prerogatives of medical research. The indiscriminate use of antibiotics in dentistry, especially for the treatment of peri-implantitis, could lead to superinfections. Alternative methods, like photodynamic therapy mediated by the use of aminolevulinic acid and a red light has been largely described, especially in dentistry, but results were encouraging against Gram-positive bacteria, but limited against Gram-negative. The effectiveness of photodynamic therapy mediated by a novel product containing aminolevulinic acid, Aladent (ALAD) has been tested in this in vitro study, against different types of bacteria particularly involved in the infections of the oral cavity and peri-implantitis. The novelty of ALAD is the marked hydrophilicity that should increase the passage of the molecule through the membrane pores of Gram-negative bacteria. Considering the novelty of the product a preliminary experiment permitted to test the effectiveness against Enterococcus faecalis after 1 h of ALAD incubation at different concentrations, with or without different timings of LED irradiation. The count of CFUs and the live/dead observation with fluorescent microscopy showed a significant reduction and killing of bacterium. Then, in the second stage, that could meet the necessity of effectiveness and the clinician's requests to reduce the timing of treatment, ALAD, with and without irradiation, was tested on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Veillonella parvula and Porphyromonas gingivalis. In particular, the efficiency of different concentrations of the product after a 25 min incubation was tested with and without the adjunctive LED irradiation for 5 min. A slight ALAD bactericidal effect was reported for all bacteria, also without LED irradiation, however, the most effective treatment was 25 min of 50% ALAD incubation followed by 5 min of a red LED. The in vitro tests demonstrated that ALAD gel with LED irradiation exerts a potent antibacterial activity on different bacteria, both Gram-positive and Gram-negative., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: To compare the effectiveness of two protocols in the treatment of peri-implant mucositis (p-iM) among cigarette smokers., Materials and Methods: Three groups were randomized into (i) single session of antimicrobial photodynamic therapy (aPDT) with mechanical debridement (MD) (Group-A), (ii) systemic AB with MD (Group-B), and (iii) MD alone (Group-C). Clinical peri-implant parameters including plaque scores (PS), bleeding on probing (BOP) and probing depth (PD) were measured at baseline, 6 weeks and 12 weeks. Microbiological parameters included the assessment of percentage level of Pseudomonas aeruginosa and Staphylococcus aureus at baseline and 12 weeks. All parameters were analyzed using Friedman test and multiple comparisons performed using Bonferroni tests. P-value less than 0.05 were considered statistically significant., Results: At 6 weeks of follow-up, there was a statistically significant reduction in PS (p < 0.001), BOP (p < 0.01), and PD (p < 0.05) among patients in groups A and B on intragroup comparison. At 12 weeks of follow-up, there was a further significant reduction in PS (p < 0.001) and BOP (p < 0.01) among patients in groups A and B on intragroup comparison but this reduction was comparable with 6-week follow-up. On inter-group comparison, only Group-A showed statistically significant reduction in BOP compared to Group-B and C at 6 weeks (p < 0.05). The levels of both P. aeruginosa and S. aureus in Group-A and Group-B showed statistically significant reductions at 12 weeks compared with baseline (p < 0.01). On inter-group comparison, Group-A and B showed no significant differences at follow-up (p > 0.05)., Conclusion: This short term clinical study suggests that aPDT as an adjunct to MD is as efficacious as adjunctive antibiotic therapy. However, additional benefits in the reduction of bleeding scores were observed for aPDT in peri-implant inflammation among cigarette smokers., (Copyright © 2019. Published by Elsevier B.V.)

Background: Recently, antimicrobial photodynamic therapy (aPDT) as an alternative treatment modality has been used adjunctively in the treatment of periodontitis and peri-implantitis. Photosensitizing agents in the form of nanoparticles have been designed for improving the efficiency of aPTD. Graphene quantum dots are a special type of nanocrystals that can promote aPDT when coupled with curcumin (Cur). The main objective of the present study was to investigate the effects of photoexcited GQD-Cur on the metabolic activity of perio-pathogen mixed biofilms., Materials and Methods: GQD-Cur was synthesized and characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible spectrometry (UV-Vis), and X-ray diffraction (XRD). The cell cytotoxicity effect of GQD-Cur was evaluated on primary human gingival fibroblast (HuGu) cells. Perio-pathogen mixed biofilms including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia photosensitized with GQD doped with Cur were irradiated with a blue LED at a wavelength of 435 ± 20 nm for 1 min, and then bacterial viability measurements were performed. The antimicrobial susceptibility profile, biofilm formation ability, amount of reactive oxygen species (ROS) released, and variations of gene expressions involved in biofilm formation were assessed., Results: The SEM, DLS, FTIR, UV-Vis spectrometry, and XRD pattern confirmed that GQD-Cur was synthesized successfully. According to the results, GQD-Cur exhibited no cytotoxicity against HuGu cells. Photoexcited GQD-Cur resulted in a significant reduction in cell viability (93%) and biofilm formation capacity (76%) of peri-pathogens compared to the control group (P < 0.05). According to the results, a significant concentration-dependent increase in the ROS generation was observed in perio-pathogens mixed cells treated with different doses of GQD-Cur-aPDT. Moreover, rcpA, fimA, and inpA gene expression profiles were downregulated by 8.1-, 9.6-, and 11.8-folds, respectively., Conclusions: Based on the results, photoexcited GQD-Cur have a high potency of perio-pathogens suppression in planktonic and biofilm forms and downregulation of the biofilm genes expression pattern was exploited as a nanoscale-based platform for periodontitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: TLR2 (Toll-like receptor 2) signaling and its downstream proinflammatory cytokines are considered to be important in the progression of peri-implantitis. A natural medicine, mangiferin has exhibited modulatory effect on TLR2 signaling and anti-inflammatory effects on different diseases. The objective of the present study is to investigate the effect of mangiferin on peri-implantitis and the potential mechanisms by administering this drug to an experimental peri-implantitis mouse model., Methods: Maxillary left first, second, and third molars of mice were extracted, and dental implants were placed in the region of the maxillary left second molars. Then, peri-implantitis was induced by tying ligatures around implants, and mangiferin was given orally to the mice. After 6-week mangiferin treatment, bone loss around the implants was detected using micro-computerized tomography (micro-CT). Alveolar bone and inflammatory infiltrate in peri-implant tissues were examined using hematoxylin and eosin (H&E) staining. Production of interleukin-6 (IL6), a TLR2 downstream proinflammatory cytokine, in the tissue surrounding implants was measured using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. IL6 protein expression and TLR2 signaling pathway activation in peri-implant tissues were detected using western blot analysis., Results: Micro-CT demonstrated reduced bone loss in peri-implantitis upon mangiferin administration. Additionally, H&E staining showed more alveolar bone and less inflammatory infiltrate in peri-implant tissues after mangiferin application. Moreover, qRT-PCR analysis demonstrated lower levels of IL6 gene expression, and western blot analysis showed decreased protein expression of IL6 and TLR2, and suppressed phosphorylation of TLR2 downstream nuclear factor-κB, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase after mangiferin treatment., Conclusions: These results suggest the suppressive effect of mangiferin on bone damage and inflammatory infiltrate in peri-implantitis. These therapeutic effects may be associated with inhibited IL6 production and reduced TLR2 signaling activation in peri-implant tissues.

Scaffolds and implants in orthopaedics and regenerative dentistry usually fail because of bacterial infections. A promising solution would be the development of biomaterials with both significant regenerative potential and enhanced antibacterial activity. Working towards this direction, fluorapatite was synthesised and doped with Sr 2+ and Ce 3+ ions in order to tailor its properties. After experiments with four common bacteria (i.e. E. Coli, S. Aureus, B. Subtilis, B. Cereus), it was found that the undoped and the Ce 3+ doped fluorapatites present better antibacterial response than the Sr 2+ doped material. The synthesised minerals were incorporated into chitosan scaffolds and tested with Dental Pulp Stem Cells (DPSCs) to check their regenerative potential. As was expected, the scaffolds containing Sr 2+ -doped fluorapatite, presented high osteoconductivity leading to the differentiation of the DPSCs into osteoblasts. Similar results were obtained for the Ce 3+ -doped material, since both the concentration of osteocalcin and the RUNX2 gene expression were considerably higher than that for the un-doped mineral. Overall, it was shown that doping with Ce 3+ retains the good antibacterial profile of fluorapatite and enhances its regenerative potential, which makes it a promising option for dealing with conditions where healing of hard tissues is compromised by bacterial contamination.

The aim of this study was to evaluate the effects of adjunct systemic antibiotic treatment with metronidazole (MTZ) and amoxicillin (AMX) in patients receiving non-surgical subgingival debridement (NSD) for peri-implantitis. Forty subjects presenting with at least one implant with severe peri-implantitis were randomized into an experimental group [treated with NSD plus MTZ (400 mg) and AMX (500 mg) three times a day for 14 days] and a control group treated with NSD plus placebo. Clinical parameters and submucosal biofilm profiles were evaluated up to 1 year post-treatment. Overall, both treatments improved clinical parameters over time. At 1 year, mean probing depth (PD), mean clinical attachment (CA) level and proportions of red complex pathogens did not differ significantly between the two groups. In addition, mean PD and CA changes to 1-year posttreatment did not differ significantly between the two groups between baseline and 1-year post-treatment. These results suggest that the addition of MTZ and AMX to the treatment protocol of patients undergoing NSD for with severe peri-implantitis does not improve the clinical and microbiological outcomes of NSD. The fact that half of the implants in both groups did not achieve clinical success (PD < 5 mm, no BoP, no bone loss) suggest that neither of the tested protocols were effective for treating severe peri-implantitis.

The concentration of methylene blue (MB) photosensitizer could affect the eradication efficacy of antimicrobial photodynamic therapy (aPDT) in the treatment of contaminated implants, which is linked to the osseointegration of the implant. We evaluated osteoblast functions on the contaminated SLA (sandblasting, large-grit and acid-etching) Ti alloy surfaces after the concentration-dependent use of MB-aPDT. Totally 1164 SLA discs were randomly distributed for the analyses of antibacterial efficacy and osteoblast functions. Gram-negative (Aggregatibacter actinomycetemcomitans; A. actinomycetemcomitans) or Gram-positive (Streptococcus mutans; S. mutans) adhered on disc samples was subjected to aPDT with different MB concentrations (200, 250, 300, 350, and 400 μg/mL) using 660 nm diode laser with maximum output 80 mW for 1 min irradiation (4.8 J/cm 2 ). Bactericidal effect was examined by viability, morphology, and lipopolysaccharide (LPS) assays. The disinfected disc surfaces by MB-aPDT to support osteoblast-like MG63 attachment, proliferation, differentiation, and mineralization were assessed for the predetermined culture time intervals. The statistical differences between the means were performed using a one-way analysis of variance (ANOVA) with a post hoc Scheffe test. The results of the morphology observation and bacterial survival examination consistently indicated a remarkably lower quantity of bacterial colonies on biofilm-contaminated surfaces after the aPDT treatment with higher MB concentration. Similarly, the higher MB concentration in aPDT resulted in the lower LPS amounts remaining on the A. actinomycetemcomitans-contaminated surfaces. Intriguingly, the expression of osteoblast cultured on disinfected surfaces using aPDT with higher MB concentration was comparable to the control without contamination. Within the limits of this in vitro model, this formulation of 400 μg/mL MB used in aPDT may be not only the lethal concentration against the 2 bacteria-contaminated implants, but it could also enhance the osteoblast functions on the contaminated implants. Nevertheless, the efficacy in the clinical practice for peri-implantitis therapy remains to be studied., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) can be used for the management of peri-implantitis. This study aimed to explore the efficacy and safety of PDT for peri-implantitis in Chinese Han patients., Methods: This was a single-centre, open-label, randomized controlled trial of participants with peri-implantitis treated at the Beijing Chao-Yang Hospital, randomized 1:1 to PDT or no PDT. PDT was performed using toluidine blue (10 mg/mL; 3 min) and a 635-nm laser (750 mW; 10 s/implant side; minimum of 60 mW/cm 2 ). The primary outcome was the decline in periodontal probing depth (PD) at 6 months. The secondary outcomes were peri-implant plaque index (PLI), sulcular bleeding index (SBI), and clinical attachment loss (CAL)., Results: PD after treatment was smaller in the PDT group (n = 66) than in controls (n = 65) (all P < 0.001 vs. baseline). At 1 month, compared with controls, the PD in the PDT group was larger, while at 3- and 6-month, the PDs were smaller (all P < 0.001). CAL, PLI and SBI in the PDT group was better (P < 0.05 vs. controls)., Conclusion: PDT combined with mechanical debridement significantly improves PD, PLI and SBI in participants with peri-implantitis. Importantly, PDT achieved a better CAL than mechanical debridement and cleaning., (© 2019 Australian Dental Association.)

Background: Antimicrobial photodynamic therapy (aPDT) is an effective adjunctive therapeutic modality for the treatment of local infections, including periodontitis and peri-implantitis. After receiving aPDT, microbial cells in the biofilm structure may produce and/ or release soluble biofilm-derived effectors (BDEs), which may affect the biology of the host cells in the community context of their surrounding microenvironment. Given the fact that no study has investigated the role of BDEs following aPDT in the pathogenesis of infectious diseases, the aim of the current study was to determine the effect of BDEs of Aggregatibacter actinomycetemcomitans following exposure to sub-lethal doses of indocyanine green (ICG)-aPDT on human gingival fibroblasts (HGFs) in terms of cytokines produced., Materials and Methods: In this study, we evaluated the effect of biofilm-conditioned medium (BCM) resulting from the treatment of A. actinomycetemcomitans biofilm with a sub-lethal dose of aPDT on cytokines production, including IL-6, IL-8, CXCL10, TGF-β, and bFGF of HGFs using enzyme-linked immunoassays (ELISA). The sensitivity of cytokines to BDEs was determined by micro-titer plates., Results: The maximal sub-lethal dose of ICG-PDT was 20.15 μM/mL ICG at a fluence of 31.2 J/cm 2 . The BCM of ICG-PDT-treated viable A. actinomycetemcomitans significantly reduced IL-6, IL-8, and CXCL10 levels compared to the BCM of untreated viable A. actinomycetemcomitans (78-, 93-, and 61.6-fold reduction, respectively; all P < 0.01). TGF-β and bFGF were strongly induced by BCM of ICG-PDT treated viable A. actinomycetemcomitans (by 57.7 and 36.1 folds, respectively; both P < 0.05). The BCM of untreated viable A. actinomycetemcomitans degraded most of the CxCL10, TGF-β and bFGF (58.8, 61.5, and 71.6%, respectively) in 24 h, while it degraded 9.3% of IL-6 and 15.1% of IL-8 after 24 h., Conclusion: The results of the current study revealed that a sub-lethal dose of ICG-aPDT through the effect of BCM on HGFs could not only significantly reduce the production of pro-inflammatory cytokines but also promoted their role in periodontal regeneration due to increasing the bFGF level. Altogether, ICG-aPDT, with it's antimicrobial effects reduces inflammation and induces of tissue regeneration resulting from BCM, can be considered an efficient adjunctive therapeutic method for the treatment of local infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The bystander effects, whereby naive (bystander) microbial cells near microbial cells directly exposed to certain treatment show responses that would not have happened in the absence of the directly targeted microbial cells, is recently documented in the field of microbiology. In this article, we discuss that substantial bystander responses are also observed after antimicrobial photodynamic therapy (aPDT) using curcumin (Cur)., Materials and Methods: Bystander effects induced by whole bacterial cell suspension (WBCS T ), cell-free supernatants fluid (CFSF T ), and bacterial cell pellet (BCP T ) obtained from A. actinomycetemcomitans culture treated with Cur-aPDT on cell survival, quorum sensing (QS) ability, metabolic activity and efflux capacity of A. actinomycetemcomitans were determined using microbial viability assay, Escherichia coli-based bioassay, XTT reduction method, and ethidium bromide (EtBr) accumulation assay, respectively., Results: A. actinomycetemcomitans cell survival reduced by 82.7% (P = 0.001) and 76.2% (P = 0.01) after exposure to WBCS T and CFSF T , respectively. The A. actinomycetemcomitans population increased by 5.5% (P = 0.7) after exposure to BCP T . Bacterial metabolic activity decreased by 42.6% (P = 0.02), 35.3% (P = 0.03), and 9.4% (P = 0.5) after exposure to WBCS T , CFSF T , and BCP T , respectively. A. actinomycetemcomitans exposed to WBCS T , CFSF T , and BCP T showed a reduction of 83.2% (P = 0.001), 77.2% (P = 0.01) and 21.9% (P = 0.09) in the QS mediator compared to the WBCS U , CFSF U , and BCP U of untreated A. actinomycetemcomitans, respectively. No significant change of the EtBr accumulation was observed in the three preparations of the Cur-aPDT-treated culture (i.e. WBCS T , CFSF T , and BCP T ) compared to their respective controls., Conclusions: The results of the current study revealed that Cur-aPDT could significantly reduce microbial cell survival, cell metabolic activity, efflux capacity, and QS ability through the bystander effects. As a result, the bystander effects of Cur-aPDT along with the direct effect of Cur-aPDT can enhance the efficiency of aPDT as an adjunct therapeutic strategy for treatment of local infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This aim of this study was to evaluate a chitosan brush for the treatment of peri-implant mucositis., Materials and Methods: A total of 11 patients with a combined total of 24 dental implants and who were diagnosed with peri-implant mucositis were included in this 6-month, split mouth, pilot clinical trial. Implants were randomly assigned to either treatment with a chitosan brush using an oscillating dental hand piece or treatment with titanium curettes. Supportive treatment was provided at 3 months. Two calibrated periodontists, blinded to treatment group, performed all examinations, including probing pocket depths (PPD) and bleeding on probing (mBoP). The changes in clinical parameters were compared between groups at 2 weeks, 4 weeks and 6 months. A Mann-Whitney U test with an alpha level of 0.05 was used for the statistical analyses., Results: Both groups demonstrated significant reductions in mBoP between baseline and 6 months. The test implants treated with the chitosan brush had a better improvement in mBoP at 2 weeks and 4 weeks compared to the implants treated with the titanium curettes. The reduction in PPD was significantly better in the test group at 4 weeks. All implants had stable bone levels, as seen on radiographs between baseline and 6 months., Conclusion: Reduced signs of inflammation were seen in both groups 6 months after the baseline treatment and 3 months after maintenance. A chitosan brush seems to be a safe and efficient device for debridement of dental implants., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Local delivery agents (LDAs) are widely used in peri-implantitis treatments. The aim of this study was to identify LDAs remaining on the dental implant surfaces and to analyze the components of these residues after applying various cleaning methods. Implants were prepared with a sand-blasted, large-grit, acid-etched surface. Four kinds of LDAs were applied on the implant surfaces: chlorhexidine gel (group 2), tetracycline solution (group 3), and 2 kinds of minocycline hydrochloride agents (groups 4 and 5). Group 1 received normal saline as a control. Two cleaning methods were applied for different durations as follows: (1) running distilled water for 10 seconds (subgroup A), 5 minutes (subgroup B), and 15 minutes (subgroup C); and (2) water spray of a dental-unit chair for 10 seconds (subgroup D) and 5 minutes (subgroup E). Scanning electron microscopy and energy-dispersive x-ray spectroscopy were used to analyze the surface morphology and residue components for all implants. The amount of LDA removed from the implant surfaces in groups 1, 2, 3, and 5 increased with the cleaning duration and pressure. However, Minocline remained coated on the implant surfaces in group 4 under all cleaning conditions. Minocline could not be cleaned off well by water due to its hydrophobicity. Therefore, directly using this agent on implant surfaces with peri-implantitis should be carefully considered. The presence of LDA residues without drug efficacies on implant surfaces might interfere with reosseointegration and act as a reservoir of microorganisms.

The purpose of this study was to determine the clinical, microbial, and radiographic effects of local minocycline combined with surgical treatment of peri-implantitis. Fifty patients with peri-implantitis were recruited, and surgical treatment with the local application of either minocycline or placebo ointment was performed. The application of minocycline was repeated with supragingival debridement at 1, 3, and 6 mo postoperatively. Plaque index, gingival index (GI), probing pocket depth (PPD), and bleeding/suppuration on probing were measured at baseline and 1-, 3-, and 6-mo evaluations. The change in supporting bone level (SBL) measured with cone beam computed tomography was analyzed between baseline and 6 mo. Microbial analysis was performed with real-time polymerase chain reaction. Both groups exhibited improvements in clinical and radiographic measurements after surgical treatment. There was a significant difference in the changes of mean PPD between the test and control groups (2.68 ± 1.73 and 1.55 ± 1.86 mm, respectively, P = 0.039). The changes of mean GI and SBL differed significantly between the groups (ΔGI: 0.83 ± 0.60 and 0.40 ± 0.68; ΔSBL: 0.72 ± 0.56 and 0.31 ± 0.49 mm, respectively, P = 0.026 and 0.014). Treatment success rates (defined as PPD <5 mm, absence of bleeding/suppuration on probing, and no further bone loss) were 66.7% and 36.3% in the test and control groups, respectively. The count of red complex bacteria tended to decrease in both groups until 6 mo; however, no significant intergroup difference was found. None of the patients in the test group carried Porphyromonas gingivalis or Tannerella forsythia at 6 mo. These findings indicate that the repeated local delivery of minocycline combined with surgical treatment provides significant benefits in terms of clinical parameters and radiographic bone fill, with a higher treatment success rate in the short healing period (cris.nih.go.kr KCT0002844).

Objective: The aims of this study were to 1) encapsulate ibuprofen (IBU) and basic fibroblast growth factor (bFGF) in a thermosensitive micellar hydrogel, 2) test the biological properties of this in situ drug delivery system, and 3) study the effect of hydrogel in promoting soft tissue healing after implant surgery and its anti-inflammatory function as an early local treatment of peri-implantitis., Materials and Methods: A thermosensitive micellar hydrogel was prepared from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone) (PECT) nanoparticles and tested in vitro using a scanning electron microscope, rheometer, UV spectrophotometer, HPLC, and transmission electron microscope., Results: The bFGF + IBU/PECT hydrogel formed a stable, water-dispersible nanoparticle core shell that was injectable at room temperature, hydrogel in situ at body temperature, and provided sustained release of both hydrophilic and hydrophobic drugs. The hydrogel promoted the proliferation and adhesion of human gingival fibroblasts, upregulated the expression of adhesion factors such as vinculin proteins, and showed anti-inflammatory properties., Conclusion: In situ preparation of IBU-and bFGF-loaded PECT hydrogel represents a promising drug delivery system with the potential to provide early local treatment for peri-implantitis., Competing Interests: Disclosure The authors report no conflicts of interest in this work.