Effects of customized CAD/CAM abutments on cytokine levels in peri-implant crevicular fluid during early implant healing: a pilot study.

OBJECTIVES: This study aimed to assess levels of biomarkers associated with inflammation and tissue destruction in peri-implant crevicular fluid (PICF) of implants provided with customized or standard healing abutments during early implant healing. MATERIALS AND METHODS: Thirty implants were placed in 22 patients with partial posterior edentulism. Subsequently, test group implants (n=15) received one-piece titanium abutments that were fabricated using computer-aided design/computer-aided manufacturing (CAD/CAM). Control group implants (n=15) were provided with standard abutments. PICF collection and standardized periapical radiographs were carried out at suture removal one week later, following crown delivery after 3 months and at 6 months. Expression of C-reactive protein (CRP), interferon-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12A, IL-17A, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase (MMP)-13, osteopontin, osteoactivin, Receptor Activator of NF-κB (RANK), and TGF-ß were analyzed using a multiplex ELISA kit. RESULTS: Both groups showed a significant decrease in protein expression of CRP, IL-1ß, IL-6, IL-8, MIP-1α, osteopontin, osteoactivin, and TGF-ß, while MMP-13 levels increased during the observation period. A rise in OPG and RANK levels was detected among customized abutments. Expression of CRP was higher, whereas IL-1ß, IL-1α, and MIP-1α were decreased in control compared to test group implants after 6 months. Marginal bone loss did not depend on abutment modality. CONCLUSIONS: Both abutment types showed distinctive temporal expression of inflammatory biomarkers during 6 months following implant placement. TRIAL REGISTRATION: ISRCTN98477184, registration date 18/05/2022 CLINICAL RELEVANCE: Customized healing abutments exert similar effects on inflammation during early implant healing compared to standard healing abutments.

Effects of enamel matrix derivative in nonsurgical periodontal therapy on pro-inflammatory profiles, microbial environment and clinical outcome: a randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the impact of enamel matrix derivative (EMD) application following subgingival instrumentation of residual pockets in periodontitis patients on inflammatory host response, microbiological composition, and clinical outcome. METHODS: In this double-blinded randomized controlled trial, a total of 22 patients with generalized periodontitis stage III or IV presenting with ≥ 6 mm probing pocket depth (PPD) at re-evaluation after initial periodontal therapy were included. Participants were randomly allocated at a 1:1 ratio to subgingival instrumentation with (EMD +) or without (EMD-) non-surgical EMD application into the pocket. PPD, clinical attachment level (CAL), bleeding on probing (BoP), plaque index (PI), as well as a panel of pro-inflammatory cytokines and periodontal pathogen count in the gingival crevicular fluid (GCF) of the respective sites were evaluated at baseline (T0) and six months afterwards (T1). RESULTS: Both treatment groups showed a significant PPD reduction (EMD + 1.33 ± 1.15 mm, p < 0.001; EMD- 1.32 ± 1.01 mm, p < 0.001) as well as CAL gain (EMD + 1.13 ± 1.58 mm, p < 0.001; EMD- 0.47 ± 1.06 mm, p = 0.005) from T0 to T1. While no intergroup differences for PPD reduction were observed, CAL gain was higher in EMD + sites compared to EMD- (p = 0.009). No essential effects on cytokine expression as well as bacterial count were detected. CONCLUSIONS: Application of EMD as an adjunct to subgingival instrumentation of residual pockets yielded benefits regarding CAL gain; however, effects on PPD reduction, inflammatory cytokines, and bacterial count were negligible. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04449393), registration date 26/06/2020. CLINICAL RELEVANCE: Based on the obtained results, additional non-surgical EMD application compared to subgingival instrumentation alone showed no clinically relevant effects on treatment outcome and underlying biological mechanisms.

Effects of Er:YAG laser irradiation of different titanium surfaces on osteoblast response.

The aim of this in vitro study was to evaluate the effects of erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation on titanium surface topography and the proliferation and differentiation of osteoblasts using standard clinical treatment settings. Er:YAG laser irradiation at two levels ((1): 160 mJ, pulse at 20 Hz; (2): 80 mJ, pulse at 20 Hz) was applied to moderately rough and smooth titanium disks before MG-63 osteoblast-like cells were cultured on these surfaces. Titanium surface and cell morphology were observed by scanning electron microscopy. Cell proliferation/viability was measured by CCK-8 test. Gene expression of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), and collagen type 1 was measured by qPCR, and OPG and OC protein production was determined by enzyme-linked immunosorbent assay. Treatment with Er:YAG laser at 160 mJ/20 Hz markedly caused heat-induced fusion of titanium and cell condensation on moderately rough surfaces, but not in smooth surfaces. MG-63 proliferation/viability decreased after 5 days in moderately rough surfaces. The expression of ALP, OC, OPG, and collagen type 1 was unaffected by laser treatment at 160 mJ/20. Laser irradiation at 80 mJ/20 Hz enhanced RANKL gene expression after 5 days in moderately rough surfaces. Study results suggest that Er:YAG laser irradiation at clinically relevant setting has no essential effect on osteogenic gene and protein expression of osteoblasts. However, surface structure, cell attachment, and proliferation are influenced by both treatment protocols, which implies that caution should be taken in the clinical treatment of peri-implant diseases when Er:YAG laser is used.

Effect of interdental brush design on plaque during nonsurgical periodontal therapy.

OBJECTIVE: The aim of this randomized controlled trial was to evaluate the interproximal cleaning efficacy of waist-shaped compared with straight soft interdental brushes in patients undergoing nonsurgical periodontal therapy. MATERIALS AND METHODS: Ten patients diagnosed with periodontitis stage II or III were scheduled for nonsurgical periodontal therapy. Baseline plaque control record (PCR), modified approximal plaque index (API), papillary bleeding index (PBI), probing pocket depth (PPD), and bleeding on probing (BOP) were evaluated. Four interdental spaces of equal sizes were determined, and baseline plaque indices (PI) were assessed on eight surfaces of the respective adjacent teeth, resulting in 640 measuring positions. Interdental brushes with a straight or waist-shaped design were randomly allocated to the right or left side, and patients received oral hygiene instructions. Follow-up measurements including PCR, API, PBI, and site-specific PI were performed during initial nonsurgical periodontal therapy sessions and reevaluation which was undertaken 8 weeks afterwards. RESULTS: PCR, API, and PBI decreased significantly compared with baseline at each time point (p < 0.001). PPD (waist-shaped, baseline 4 mm (range, 2-9 mm) vs. reevaluation 3 mm (range, 1-6 mm); p < 0.001; straight, baseline 4 mm (range, 2-10) vs. reevaluation 3 mm (range, 1-6) mm; p < 0.001) and BOP (p = 0.008) showed significant reduction in both groups. Sub-analysis of site-specific areas including line angles and interproximal areas revealed no significant reduction of plaque during the observation period between both brush designs. No difference between straight and waist-shaped brushes regarding PPD or BOP decrease was found. CONCLUSION: The efficacy of both interdental brush designs concerning plaque control in patients undergoing nonsurgical periodontal therapy was similar. CLINICAL RELEVANCE: The use of interdental brushes is essential for biofilm removal in patients during initial periodontal therapy, regardless of brush design. CLINICAL TRIAL REGISTRATION: ISRCTNregistry (#ISRCTN24498365), http://www.isrctn.com/ISRCTN24498365.

Short-term results of the combined application of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser and erbium-doped yttrium aluminum garnet (Er:YAG) laser in the treatment of periodontal disease: a randomized controlled trial.

OBJECTIVES: Nd:YAG and Er:YAG lasers have been previously used as an adjunct in periodontal therapy. The aim of this single-blinded randomized controlled clinical trial was to evaluate the efficacy of a combined application of Nd:YAG and Er:YAG laser irradiation in periodontal treatment. MATERIALS AND METHODS: Twenty-two patients with at least one site of ≥ 6 mm periodontal probing depth (PPD) after mechanical debridement with curettes and sonic instruments at periodontal reevaluation were included in the study. Patients were randomly allocated at a 1:1 ratio to either a combined Nd:YAG/Er:YAG laser therapy (test group) or a "turned off" laser therapy (control group). The Nd:YAG laser was used for periodontal pocket deepithelialization and to stabilize the resulting blood clot. The Er:YAG laser was primarily used for root surface modification. PPD (mm), clinical attachment level (CAL, mm), and bleeding on probing (BOP, +/-) at the site of laser treatment were evaluated at baseline and 2 months after treatment. RESULTS: The mean improvements from baseline to 2-month follow-up for PPD were significantly better in the laser group (2.05 ± 0.82 mm) compared to the control group (0.64 ± 0.90 mm; p = 0.001). Likewise, the gain in CAL was significantly better in the laser group (1.50 ± 1.10 mm) than in the control group (0.55 ± 1.01mm; p = 0.046). CONCLUSIONS: The combined application of Nd:YAG and Er:YAG laser irradiation as an adjunct to conventional non-surgical therapy showed a significant beneficial effect on periodontal treatment results. CLINICAL RELEVANCE: Combined Nd:YAG and Er:YAG laser irradiation could be a useful procedure additionally to conventional non-surgical periodontal therapy to improve periodontal treatment results. CLINICAL TRIAL REGISTRATION: ISRCTN registry #ISRCTN32132076.

Impact of 0.1% octenidine mouthwash on plaque re-growth in healthy adults: a multi-center phase 3 randomized clinical trial.

OBJECTIVES: To investigate plaque inhibition of 0.1% octenidine mouthwash (OCT) vs. placebo over 5 days in the absence of mechanical plaque control. MATERIALS AND METHODS: For this randomized, placebo-controlled, double-blind, parallel group, multi-center phase 3 study, 201 healthy adults were recruited. After baseline recording of plaque index (PI) and gingival index (GI), collection of salivary samples, and dental prophylaxis, subjects were randomly assigned to OCT or placebo mouthwash in a 3:1 ratio. Rinsing was performed twice daily for 30 s. Colony forming units in saliva were determined before and after the first rinse. At day 5, PI, GI, and tooth discoloration index (DI) were assessed. Non-parametric van Elteren tests were applied with a significance level of p < 0.05. RESULTS: Treatment with OCT inhibited plaque formation more than treatment with placebo (PI: 0.36 vs. 1.29; p < 0.0001). OCT reduced GI (0.04 vs. placebo 0.00; p = 0.003) and salivary bacterial counts (2.73 vs. placebo 0.24 lgCFU/ml; p < 0.0001). Tooth discoloration was slightly higher under OCT (DI: 0.25 vs. placebo 0.00; p = 0.0011). Mild tongue staining and dysgeusia occurred. CONCLUSIONS: OCT 0.1% mouthwash inhibits plaque formation over 5 days. It therefore can be recommended when regular oral hygiene is temporarily compromised. CLINICAL RELEVANCE: When individual plaque control is compromised, rinsing with octenidine mouthwash is recommended to maintain healthy oral conditions while side effects are limited.

Which substances loaded onto collagen scaffolds influence oral tissue regeneration?-an overview of the last 15 years.

BACKGROUND: Collagen scaffolds are widely used for guided bone or tissue regeneration. Aiming to enhance their regenerative properties, studies have loaded various substances onto these scaffolds. This review aims to provide an overview of existing literature which conducted in vitro, in vivo, and clinical testing of drug-loaded collagen scaffolds and analyze their outcome of promoting oral regeneration. MATERIALS AND METHODS: PubMed, Scopus, and Ovid Medline® were systematically searched for publications from 2005 to 2019. Journal articles assessing the effect of substances on oral hard or soft tissue regeneration, while using collagen carriers, were screened and qualitatively analyzed. Studies were grouped according to their used substance type-biological medical products, pharmaceuticals, and tissue-, cell-, and matrix-derived products. RESULTS: A total of 77 publications, applying 36 different substances, were included. Collagen scaffolds were demonstrating favorable adsorption behavior and release kinetics which could even be modified. BMP-2 was investigated most frequently, showing positive effects on oral tissue regeneration. BMP-9 showed comparable results at lower concentrations. Also, FGF2 enhanced bone and periodontal healing. Antibiotics improved the scaffold's anti-microbial activity and reduced the penetrability for bacteria. CONCLUSION: Growth factors showed promising results for oral tissue regeneration, while other substances were investigated less frequently. Found effects of investigated substances as well as adsorption and release properties of collagen scaffolds should be considered for further investigation. CLINICAL RELEVANCE: Collagen scaffolds are reliable carriers for any of the applied substances. BMP-2, BMP-9, and FGF2 showed enhanced bone and periodontal healing. Antibiotics improved anti-microbial properties of the scaffolds.

Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis.

BACKGROUND: Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The biological effects of bisphosphonates are thought to be mainly associated with osteoclasts inhibition, whereas their effects on osteoblast function are unclear. A potential of bisphosphonate coated surfaces to stimulate osteoblast differentiation was investigated by several in vitro studies with contradictory results. The purpose of this systematic review and meta-analysis was to evaluate the effect of bisphosphonate coated implant surfaces on alkaline phosphatase activity in osteoblasts. METHODS: In vitro studies that assessed alkaline phosphatase activity in osteoblasts following cell culture on bisphosphonate coated titanium surfaces were searched in electronic databases PubMed/MEDLINE, Scopus and ISI Web of Science. Animal studies and clinical trials were excluded. The literature search was restricted to articles written in English and published up to August 2019. Publication bias was assessed by the construction of funnel plots. RESULTS: Eleven studies met the inclusion criteria. Meta-analysis showed that coating of titanium surfaces with bisphosphonates increases alkaline phosphatase activity in osteoblasts after 3 days (n = 1), 7 (n = 7), 14 (n = 6) and 21 (n = 3) days. (7 days beta coefficient = 1.363, p-value = 0.001; 14 days beta coefficient = 1.325, p-value < 0.001; 21 days beta coefficient = 1.152, p-value = 0.159). CONCLUSIONS: The meta-analysis suggests that bisphosphonate coatings of titanium implant surfaces may have beneficial effects on osteogenic behaviour of osteoblasts grown on titanium surfaces in vitro. Further studies are required to assess to which extent bisphosphonates coating might improve osseointegration in clinical situations.

Thoracolumbar Rotation During Tai Chi Movements-A Biomechanical Analysis of the Entire Peking Style Routine.

The impact of spinal mobility and sagittal spinal shape on the development of balance impairment supports the hypothesis that enhancing spine flexibility results in an improvement in postural balance ability. Therefore, the aim of this study was to investigate whether the range of motion of thoracolumbar rotation during the movements of the Tai Chi Peking style routine is sufficient to improve thoracolumbar flexibility. Three-dimensional kinematic and kinetic data were collected from eight athletes of the German Wushu Federation, while performing all movements of the entire Peking style routine (1) in a competition version corresponding to national/international championships and (2) in a health sport version performed with shorter and higher stances (i.e. a smaller distance between the feet and thus less knee flexion). For each movement the total mean and standard deviation values for the total range of motion of thoracolumbar rotation was calculated. Statistical analysis was performed using the Wilcoxon signed-rank test for paired differences. Eight movements showed major differences (10.12-19.73°) between the two versions. For the remaining movements, only minor differences (0.7-9.56°) were observed. All movements performed on both sides showed no significant lateral differences. Most of the Tai Chi movements, regardless of the performed version, cover a range of motion of thoracolumbar rotation that has the potential to lead to an improvement of thoracolumbal spine flexibility with appropriate training. The most effective single movements (25.97-72.22°) are Brush Knee and Step Forward, Step Back and Repulse Monkey, Grasp the Sparrow's Tail, Wave Hand in the Clouds, and Fair Lady Weaves with Shuttle.

Effect of Tai Chi on muscle strength, physical endurance, postural balance and flexibility: a systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of Tai Chi training on muscle strength, physical endurance, postural balance and flexibility, as measured by tests commonly used in health-related fitness or competitive sports contexts. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The following databases were searched up to 31 July 2020: CINAHL, Cochrane Library, MEDLINE via PubMed and SPORTDiscus. ELIGIBILITY CRITERIA FOR STUDIES: Inclusion: (1) Randomised controlled trials published in German or English; (2) Tai Chi used as an intervention to improve physical performance; (3) Test methods commonly used in health-related fitness or competitive sports and (4) Participants aged ≥16 years (irrespective of health status). Exclusion: (1) Studies not focusing on Tai Chi or including Tai Chi mixed with other interventions and (2) Modified or less than eight Tai Chi movements. RESULTS: Out of 3817 records, 31 studies were included in the review, 21 of them in the meta-analysis. Significant improvements in handgrip strength (2.34 kg, 95% CI 1.53 to 3.14), walking distance during 6 min (43.37 m, 95% CI 29.12 to 57.63), standing time in single-leg-stance with open eyes (6.41 s, 95% CI 4.58 to 8.24) and thoracolumbar spine flexibility (2.33 cm, 95% CI 0.11 to 4.55) were observed. CONCLUSION: Tai Chi training seems to moderately improve physical fitness when evaluated by tests used in health-related fitness or competitive sports. Moreover, thoracolumbar spine flexibility seems to be a factor in the improvement of postural balance. Further research is needed, including younger healthy participants performing a widely used, standardised form (eg, Peking-style routine) with high-intensity movements (eg, use of lower stances).

Characteristics and frequency distribution of bone defect configurations in peri-implantitis lesions-A series of 193 cases.

BACKGROUND: Knowledge on peri-implantitis bone defect characteristics and predictors is still limited. PURPOSE: To describe peri-implantitis bone defect characteristics and identify possible predictors. METHODS: Various parameters at patient- (age, gender, smoking, and supra-structure), implant- (surface, type, connection, platform, and misfit), and site level (region, alveolar ridge position, defect characteristics, neighboring structure) were recorded retrospectively. RESULTS: Among 193 implants, the most prevalent defects were class Ic (25.4%), and Id (23.8%); a previously non-described category "class Id with only one bone wall" was frequently observed (11.9%). Mean intrabony defect depth and width ranged from 4.5 to 6.2 mm and from 2.7 to 2.9 mm, respectively; mean dehiscence extent ranged from 2.8 to 7.0 mm. A total of 37.8% of the defects presented horizontal bone loss and an intrabony component; in 52.7% of the implants, total defect extent was >6 mm. Jaw region, implant position within the alveolar ridge, and implant/abutment misfit showed significant associations either to defect configuration and/or defect extent. CONCLUSION: (a) Most common peri-implantitis defects exhibited a combination of intrabony component and a buccal/oral dehiscence, while purely circumferential defects were relatively seldom; (b) implants with defects with bone dehiscence were placed more frequently closer to the lateral aspect of the ridge harboring the dehiscence; (c) implants placed in the lower anterior region had the highest risk for more severe peri-implant bone loss; and (d) peri-implant bone defects with only a single bone wall appropriate for regenerative procedure were relatively frequent.

Impact of Implant Surface Material and Microscale Roughness on the Initial Attachment and Proliferation of Primary Human Gingival Fibroblasts.

Due to the rising demand for zirconia (Zr) based implant systems, it is important to understand the impact of Zr and titanium (Ti) implants and particularly their topography on soft tissue healing. As human gingival fibroblasts (hGFs) are the predominant cells in peri-implant soft tissue, we focused on examining the effect of implant material and surface roughness on hGFs' initial attachment, growth and the expression of proteins involved in the focal adhesion. hGFs isolated from eight healthy donors were cultured on the following surfaces: smooth titanium machined surface (TiM), smooth zirconia machined surface (ZrM), moderately rough titanium surface (SLA), or moderately rough zirconia surface (ZLA) for up to 14 days. The initial attachment of hGFs was evaluated by scanning electron microscopy. Cell proliferation/viability was assessed by cell counting kit 8. Focal adhesion and cytoskeleton were visualized by a focal adhesion staining kit. The gene expression of focal adhesion kinase (FAK), α-smooth muscle actin (α-SMA), and integrin subunits ITG-ß1, ITG-ß4, ITG-α4, ITG-α5, ITG-α6, was evaluated by qPCR. Cell proliferation/viability was slightly decreased by moderately rough surfaces, whereas no effect of surface material was observed. Cell morphology was strikingly different between differently treated surfaces: on machined surfaces, cells had elongated morphology and were attached along the grooves, whereas on moderately rough surfaces, cells were randomly attached. Surface roughness had a more pronounced effect on the gene expression compared to the surface material. The expression of FAK, α-SMA, ITG-ß4, ITG-α5, and ITG-α6 was enhanced by moderately rough surfaces compared to smooth surfaces. Within the limitations of this in vitro study, it can be concluded that the behavior of primary hGFs is primarily affected by surface structure, whereas no apparent advantage of Zr over Ti could be observed.

Effect of Multi-Phosphonate Coating of Titanium Surfaces on Osteogenic Potential.

The aim of this study was to evaluate the impact of a novel multi-phosphonate (MP) coating strategy of dental implant surfaces on the expression of osteogenesis-related factors in vitro. MG-63 human osteoblast-like cells, bone marrow mesenchymal stem cells (BM-MSCs), and human periodontal ligament stem cells (hPDLSCs) were cultured separately on titanium disks with and without MP coating. Cell attachment was visualized by focal adhesion and actin cytoskeleton staining. The proliferation and gene expression of the markers related to osteogenesis and bone turnover were measured after 48 and 120 h of cell culture. Actin cytoskeleton assembly and focal adhesion were similar between test surfaces within each cell type but differed from those on tissue culture plastic (TCP). The proliferation of MG-63 cells and PDLSCs was comparable on all surfaces, while BM-MSCs showed an increase on tissue culture plastic (TCP) versus titanium. The gene expression of osteoprotegerin and receptor activator of nuclear factor-kappa B ligand was higher in MG-63 cells grown on MP-coated surfaces. At the same time, osteocalcin was decreased compared to the other surfaces. Collagen type I gene expression after 120 h was significantly lower in hPDLSCs cultivated on MP-coated surfaces. Within the limitations of this study, MP coating on titanium surfaces might have a slight beneficial effect on bone turnover in vitro.

Effect of implant surface material and roughness to the susceptibility of primary gingival fibroblasts to inflammatory stimuli.

OBJECTIVES: The impact of the implant surface material and roughness on inflammatory processes in peri-implantitis is not entirely clear. Hence, we investigated how titanium and zirconia surfaces with different roughness influence the susceptibility of primary human gingival fibroblasts to different inflammatory stimuli. METHODS: Primary human gingival fibroblasts were isolated from 8 healthy individuals and cultured on following surfaces: smooth titanium machined surface (TiM), smooth zirconia machined surface (ZrM), moderately rough titanium surface (SLA), or moderately rough zirconia surface (ZLA). Subsequently, stimulation with one of the following stimuli was performed: Porphyromonas gingivalis lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß. The resulting production of IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 was measured by qPCR and ELISA. RESULTS: P. gingivalis LPS induced IL-6 and MCP-1 production was slightly higher on titanium surfaces compared to zirconia surfaces. IL-1ß induced IL-6 production was not affected by any surface characteristic. The production of MCP-1 in response to IL-1ß was higher on smooth compared to rough surfaces and was not affected by the material. The production of IL-6 and MCP-1 in response to TNF-α was most strongly affected by surface characteristics. Higher production of these cytokine was observed on smooth compared to rough surfaces and on titanium compared to zirconia surfaces. Surface characteristics had only minor effects on IL-8 production. SIGNIFICANCE: The susceptibility of primary gingival fibroblasts to inflammation depends on various factors, such as surface material, surface roughness and the nature of inflammatory stimuli. All these factors might determine susceptibility to peri-implantitis.

Relevance of the plasminogen system in physiology, pathology, and regeneration of oral tissues - From the perspective of dental specialties.

Plasmin is a proteolytic enzyme that is crucial in fibrinolysis. In oral tissues, the plasminogen system plays an essential role in physiological and pathological processes, which in addition to fibrinolysis include degradation of extracellular matrix, inflammation, immune response, angiogenesis, tissue remodeling, cell migration, and wound healing. Oral tissues reveal a change in the plasminogen system during pathological processes such as periodontitis, peri-implantitis, or pulpitis, as well as in response to mechanical load. The plasminogen system is also a key element in tissue regeneration. The number of studies investigating the plasminogen system in dentistry have grown continuously in recent years, highlighting its increasing relevance in dental medicine. In this review, we present the diverse functions of the plasminogen system in physiology and its importance for dental specialists in pathology and regeneration. We thus provide an overview of the current knowledge on the role of the plasminogen system in the different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery.

L-mimosine and dimethyloxaloylglycine decrease plasminogen activation in periodontal fibroblasts.

BACKGROUND: The use of prolyl hydroxylase inhibitors such as l-mimosine (L-MIM) and dimethyloxaloylglycine (DMOG) to improve angiogenesis is a new approach for periodontal regeneration. In addition to exhibiting pro-angiogenic effects, prolyl hydroxylase inhibitors can modulate the plasminogen activator system in cells from non-oral tissues. This study assesses the effect of prolyl hydroxylase inhibitors on plasminogen activation by fibroblasts from the periodontium. METHODS: Gingival and periodontal ligament fibroblasts were incubated with L-MIM and DMOG. To investigate whether prolyl hydroxylase inhibitors modulate the net plasminogen activation, kinetic assays were performed with and without interleukin (IL)-1. Moreover, plasminogen activators and the respective inhibitors were analyzed by casein zymography, immune assays, and quantitative polymerase chain reaction. RESULTS: The kinetic assay showed that L-MIM and DMOG reduced plasminogen activation under basal and IL-1-stimulated conditions. Casein zymography revealed that the effect of L-MIM involves a decrease in urokinase-type plasminogen activator activity. In agreement with these findings, reduced levels of urokinase-type plasminogen activator and elevated levels of plasminogen activator inhibitor 1 were observed. CONCLUSION: L-MIM and DMOG can reduce plasminogen activation by fibroblasts from the gingiva and the periodontal ligament under basal conditions and in the presence of an inflammatory cytokine.