Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo.

Introduction: Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. Pseudomonas aeruginosa is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response. Aim: This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response. Material and methods: In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology. Results: In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1ß, IL-6, and IL-1α secretion, as compared with untreated supernatants. Conclusion: In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.

Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg2+ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg2+ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.

Achieving stomal continence with an ileal pouch and a percutaneous implant.

In this study, a soft-tissue-anchored, percutaneous port used as a mechanical continence-preserving valve in reservoir ileo- and urostomies was functionally and morphologically evaluated in eight dogs. During follow-up, the skin failed to attach to the implant, but the intestine inside the stoma port appeared to be attached to the mesh. After reaching adequate reservoir volume, the urostomies were rendered continent by attaching a lid to the implant. The experiments were ended at different time intervals due to implant-related adverse events. In only one case did the histological evaluation reveal integration at both the implant-intestine and implant-skin interfaces, with a low degree of inflammation and the absence of bacterial colonisation. In the remaining cases, integration was not obtained and instead mucosal downgrowth and biofilm formation were observed. The skin-implant junction was characterised by the absence of direct contact between the epidermis and the implant. Varying degrees of epidermal downgrowth, granulation tissue formation, inflammatory cell infiltration and bacterial growth and biofilm formation were prominent findings. In contrast, the subcutaneously located anchor part of the titanium port was well integrated and encapsulated by fibrous tissue. These results demonstrate the opportunity to achieve integration between a soft-tissue-anchored titanium port, skin and intestine. However, predictable long-term function could not be achieved in these animal models due to implant- and non-implant-related adverse events. Unless barriers at both the implant-skin and implant-intestine junctions are created, epidermal and mucosal downward migration and biofilm formation will jeopardise implant performance.

Compromised extraction sockets: a new classification and prevalence involving both soft and hard tissue loss.

PURPOSE: Previous studies have solely focused on fresh extraction sockets, whereas in clinical settings, alveolar sockets are commonly associated with chronic inflammation. Because the extent of tissue destruction varies depending on the origin and the severity of inflammation, infected alveolar sockets may display various configurations of their remaining soft and hard tissues following tooth extraction. The aim of this study was to classify infected alveolar sockets and to provide the appropriate treatment approaches. METHODS: A proposed classification of extraction sockets with chronic inflammation was developed based upon the morphology of the bone defect and soft tissue at the time of tooth extraction. The prevalence of each type of the suggested classification was determined retrospectively in a cohort of patients who underwent, between 2011 and 2015, immediate bone grafting procedures (ridge preservation/augmentation) after tooth extractions at Seoul National University Dental Hospital. RESULTS: The extraction sockets were classified into 5 types: type I, type II, type III, type IV (A & B), and type V. In this system, the severity of bone and soft tissue breakdown increases from type I to type V, while the reconstruction potential and treatment predictability decrease according to the same sequence of socket types. The retrospective screening of the included extraction sites revealed that most of the sockets assigned to ridge preservation displayed features of type IV (86.87%). CONCLUSIONS: The present article classified different types of commonly observed infected sockets based on diverse levels of ridge destruction. Type IV sockets, featuring an advanced breakdown of alveolar bone, appear to be more frequent than the other socket types.

Effects of hyaluronic acid and deproteinized bovine bone mineral with 10% collagen for ridge preservation in compromised extraction sockets.

BACKGROUND: The aim of this study was to evaluate the efficacy of deproteinized bovine bone mineral with 10% collagen (DBBM-C) soaked with hyaluronic acid (HA) for ridge preservation in compromised extraction sockets. METHODS: Bilateral third, fourth premolars and first molar were hemisected, distal roots were extracted, and then combined endodontic periodontal lesion was induced in the remaining mesial roots. After 4 months, the mesial roots were extracted and the following four treatments were randomly performed: Absorbable collagen sponge (ACS), ACS soaked with HA (ACS+HA), ridge preservation with DBBM-C covered with a collagen membrane (RP), ridge preservation with DBBM-C mixed with HA and covered with a collagen membrane (RP+HA). Animals were sacrificed at 1 and 3 months following treatment. Ridge dimensional changes and bone formation were examined using microcomputed tomography, histology, and histomorphometry. RESULTS: At 1 month, ridge width was significantly higher in the RP and RP+HA groups than in the ACS and ACS+HA groups, while the highest proportion of mineralized bone was observed in ACS+HA group. At 3 months, ridge width remained significantly higher in the RP and RP+HA groups than in the ACS and ACS+HA groups. ACS+HA and RP+HA treatments featured the highest proportion of mineralized bone and bone volume density compared with the other groups. No statistical difference was observed between ACS+HA and RP+HA treatments. CONCLUSIONS: Ridge preservation with the mixture DBBM-C/HA prevented dimensional shrinkage and improved bone formation in compromised extraction sockets at 1 and 3 months.

Is ridge preservation effective in the extraction sockets of periodontally compromised teeth? A randomized controlled trial.

OBJECTIVE: To verify whether ridge preservation is effective in the reduction of dimensional loss and in bone formation compared to spontaneous healing in extraction sockets of periodontally compromised teeth. METHODS: Twenty-six subjects requiring tooth extraction for stage III/IV periodontitis were randomly assigned to one of two interventions: alveolar ridge preservation using collagenated bovine bone mineral and a resorbable collagen membrane (test, RP) or spontaneous healing (control, SH). Six months later, postoperative cone-beam computed tomography (CBCT) was performed to measure the linear and volumetric changes of the sockets compared to baseline scans. Biopsies were retrieved at the implant site for histomorphometric calculations. Nonparametric tests were applied for statistical analysis. RESULTS: Significantly less shrinkage occurred in RP compared to SH, mainly in the crestal zone. The width loss difference between groups was 3.3 mm and 2.2 mm at 1 mm and 3 mm below the crest, respectively (p < .05). RP yielded a gain in socket height of 0.25 mm, whereas a loss of -0.39 mm was observed in SH (p < .05). The percentage of volume loss recorded in RP was also less than that recorded in SH (-26.53% vs -50.34, p < .05). Significantly less bone proportion was detected in biopsies from RP (30.1%) compared with SH (53.9%). A positive association between baseline bone loss and ridge shrinkage was found in SH but not in RP. CONCLUSION: Ridge preservation in extraction sockets of periodontally compromised teeth was effective in reducing the amount of ridge resorption.

Association of prosthetic features and peri-implantitis: A cross-sectional study.

OBJECTIVE: To identify the influence of prosthetic features through a comprehensive analysis with other known risk factors. MATERIALS AND METHODS: A total of 169 patients (n = implants: 349) was retrospectively included in the present study. Peri-implantitis was diagnosed based on peri-implant bone loss and probing depth. Using radiographs taken 1 and 5 years following prosthesis insertion, the following features were determined: peri-implant marginal bone loss (MBL), emergence angle (EA), emergence profile (EP) and crown/implant ratio (CIR). The splinted position of prosthesis was also recorded. Multivariable generalized estimating equation was used to analyse the influence of each feature on the prevalence of peri-implantitis. The final prediction model was constructed by Cox proportional hazard regression analysis. RESULTS: The EA showed a significant correlation with MBL. A statistically greater prevalence of peri-implantitis was observed if EA ≥ 30 degrees, when EP is convex and in middle implant splinted with both mesial and distal adjacent implants in bone-level implant. A similar correlation was not observed in tissue-level implants. CIR had no significant effect on the prevalence of peri-implantitis. CONCLUSION: Over-contoured implant prosthesis is a critical local confounder for peri-implantitis. The implant splinted to both mesial and distal adjacent implant has a higher risk of peri-implantitis.

Oral Soft Tissue Regeneration Using Nano Controlled System Inducing Sequential Release of Trichloroacetic Acid and Epidermal Growth Factor.

BACKGROUND: The effect of nano controlled sequential release of trichloroacetic acid (TCA) and epidermal growth factor (EGF) on the oral soft tissue regeneration was determined. METHODS: Hydrophobically modified glycol chitosan (HGC) nano controlled system was developed for the sequential release of TCA and EGF, and the release pattern was identified. The HGC-based nano controlled release system was injected into the critical-sized defects created in beagles' palatal soft tissues. The palatal impression and its scanned body was obtained on various time points post-injection, and the volumetric amount of soft tissue regeneration was compared among the three groups: CON (natural regeneration control group), EXP1 (TCA-loaded nano controlled release system group), EXP2 (TCA and EGF individually loaded nano controlled release system). DNA microarray analysis was performed and various soft tissue regeneration parameters in histopathological specimens were measured. RESULTS: TCA release was highest at Day 1 whereas EGF release was highest at Day 2 and remained high until Day 3. In the volumetric measurements of impression body scans, no significant difference in soft tissue regeneration between the three groups was shown in two-way ANOVA. However, in the one-way ANOVA at Day 14, EXP2 showed a significant increase in soft tissue regeneration compared to CON. High correlation was determined between the histopathological results of each group. DNA microarray showed up-regulation of various genes and related cell signaling pathways in EXP2 compared to CON. CONCLUSION: HGC-based nano controlled release system for sequential release of TCA and EGF can promote regeneration of oral soft tissue defects.

Chemical Regeneration of Wound Defects: Relevance to the Canine Palatal Mucosa and Cell Cycle Up-Regulation in Human Gingival Fibroblasts.

Background: Trichloroacetic acid (TCA) is an agent widely applied in dermatology for skin regeneration. To test whether TCA can offer an advantage for the regeneration of oral soft tissue defects, the cellular events following TCA application were explored in vitro and its influence on the oral soft tissue wound healing was evaluated in a canine palate model. Methods: The cytotoxicity and growth factor gene expression in human gingival fibroblasts were tested in vitro following the application of TCA at four concentrations (0.005%, 0.05%, 0.5% and 1%) with different time intervals (0, 3, 9 and 21 h). One concentration of TCA was selected to screen the genes differentially expressed using DNA microarray and the associated pathways were explored. TCA was injected in open wound defects of the palatal mucosa from beagle dogs (n = 3) to monitor their healing and regeneration up to day 16-post-administration. Results: While the 0.5-1% concentration induced the cytoxicity, a significantly higher expression of growth factor genes was observed after 3 and 9 h following the 0.5% TCA application in comparison to other groups. DNA microarray analysis in 0.5% TCA group showed 417 genes with a significant 1.5-fold differential expression, involving pathways of cell cycle, FoxO signaling, p53 signaling, ubiquitin mediated proteolysis and cAMP signaling. In vivo results showed a faster reepithelialization of TCA-treated wounds as compared to spontaneous healing. Conclusion: TCA promoted the healing and regeneration of oral soft tissue wound defects by up-regulating the cell cycle progression, cell growth, and cell viability, particularly at a concentration of 0.5%.

Healing kinetics of oral soft tissue wounds treated with recombinant epidermal growth factor: Translation from a canine model.

OBJECTIVE: To test whether or not topically administered recombinant human epidermal growth factor (rhEGF) accelerates the early healing phase of oral soft tissue wounds. METHODS: One day following the creation of palatal defects (n = 6/animal), 14 dogs were allocated to one of the following five groups: spontaneous healing (SH), vehicle ointment (V), vehicle ointment + rhEGF at concentrations of 1 µg/g (EGF1), 10 µg/g (EGF10) or 50 µg/g (EGF50). Topical administration of ointments was repeated twice per day until sacrifice at days 8 and 16. Wound area was clinically monitored. Keratinocytes proliferation (Ki67-immunolabelling), inflammatory response (IR) and areas of collagen (C) and granulation tissue (GT) were histologically measured. Kruskal-Wallis test with Dunnett correction was used for multiple group statistical comparisons. RESULTS: Clinically, in comparison with SH, a significantly smaller wound area was observed in groups EGF1 and EGF10 at day 8 (p < 0.05). At day 16, wound closure reached 97.8% in group EGF1 compared to 83.2% in group SH, albeit no statistically different. Histologically, at day 8, significantly more GT was observed in group EGF10 compared to all other groups (p < 0.05). At day 16, in addition to a higher Ki67-immunolabelling, groups EGF1 and EGF10 demonstrated a significant decrease in GT and IR with more deposition of C compared to the other groups (p < 0.05). CONCLUSION: Application of rhEGF enhanced the early healing of acute oral soft tissue wounds compared to SH, predominantly at concentrations of 1 and 10 µg/g.

Biomodification of compromised extraction sockets using hyaluronic acid and rhBMP-2: An experimental study in dogs.

BACKGROUND: This experimental study aims to evaluate the effect of hyaluronic acid on healing of infected extraction sockets compared with recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: Both third and fourth mandibular premolars of six beagle dogs were hemisected, and the distal roots were extracted at baseline. Subsequently, combined endodontic-periodontic lesions were induced at the remaining mesial roots. After 4 months, the mesial roots on both sides of the mandible were removed. Four sockets per dog were randomly allocated to four groups: Group 1, Control; Group 2, only absorbable collagen sponge (ACS: carrier); Group 3, 1% hyaluronic acid (HA) gel + ACS; and Group 4, rhBMP-2 + ACS. After 3 months of healing, the dogs were euthanized for microcomputed tomography and histologic analysis. RESULTS: After the lesion induction period (4 months), communication between the periodontal lesion and endodontic periapical lesion was observed at all remaining mesial roots. Alveolar bone overgrowth was observed in groups 3 and 4, but bone volume density was not significantly different among all groups. At the crestal portion, mineralization, and osteocalcin expression were higher in groups 3 and 4 than in groups 1 and 2. CONCLUSION: Treatment with HA can promote bone formation and improve the wound healing rate comparable to rhBMP-2 in infected extraction sockets.

Effects of quorum-sensing inhibition on experimental periodontitis induced by mixed infection in mice.

This study aimed to verify, in in vivo settings, whether quorum-sensing inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial colonization of periodontal tissues. In BALB/c mice, periodontitis was induced through oral inoculation with P. gingivalis and F. nucleatum six times during a 42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were administered simultaneously with bacterial infection. Linear and volumetric modifications of interproximal alveolar bone levels were compared between groups using micro-computed tomography. Total bacteria, and P. gingivalis and F. nucleatum DNA in periodontal tissues, were quantified using real-time PCR. Radiographic linear measurements demonstrated a significant reduction of alveolar bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors when compared with the co-infection group. This was confirmed by a significant increase of residual bone volume in the test group. While total bacterial genes in the treatment group significantly decreased by 93% in periodontal tissue samples when quorum sensing inhibitors were administered, no significant differences of P. gingivalis DNA were found. Quorum sensing inhibitors reduced periodontal breakdown and bacterial infection in periodontal tissues after co-infection with P. gingivalis and F. nucleatum.

Oral tissue response to soft tissue expanders prior to bone augmentation: in vitro analysis and histological study in dogs.

PURPOSE: To determine whether the swelling and mechanical properties of osmotic self-inflating expanders allow or not the induction of intraoral soft tissue expansion in dogs. METHODS: Three different volumes (0.15, 0.25, and 0.42 mL; referred to respectively as the S , M , and L groups) of soft tissue expanders (STEs) consisting of a hydrogel core coated with a silicone-perforated membrane were investigated in vitro to assess their swelling behavior (volume swelling ratio) and mechanical properties (tensile strength, tensile strain). For in vivo investigations, the STEs were subperiosteally inserted for 4 weeks in dogs (n=5). Soft tissue expansion was clinically monitored. Histological analyses included the examination of alveolar bone underneath the expanders and thickness measurements of the surrounding fibrous capsule. RESULTS: The volume swelling ratio of all STEs did not exceed 5.2. In tensile mode, the highest mean strain was registered for the L group (98.03±0.3 g/cm), whereas the lowest mean value was obtained in the S group (81.3±0.1 g/cm), which was a statistically significant difference (P<0.05). In addition, the S and L groups were significantly different in terms of tensile strength (1.5±0.1 g/cm for the S group and 2.2±0.1 g/cm for the L group, P<0.05). Clinical monitoring showed successful dilatation of the soft tissues without signs of inflammation up to 28 days. The STEs remained volumetrically stable, with a mean diameter in vivo of 6.98 mm, close to the in vitro post-expansion findings (6.69 mm). Significant histological effects included highly vascularized collagen-rich fibrous encapsulation of the STEs, with a mean thickness of 0.67±0.12 mm. The bone reaction consisted of resorption underneath the STEs, while apposition was observed at their edges. CONCLUSIONS: The swelling and mechanical properties of the STEs enabled clinically successful soft tissue expansion. A tissue reaction consisting of fibrous capsule formation and bone loss were the main histological events.

Influence of rhBMP-2 on Guided Bone Regeneration for Placement and Functional Loading of Dental Implants: A Radiographic and Histologic Study in Dogs.

PURPOSE: Evidence on the outcomes of functional loading placed in recombinant human bone morphogenetic protein 2 (rhBMP-2)/acellular collagen sponge (ACS)-induced bone is lacking. The aim of this study was to verify whether guided bone regeneration (GBR) with rhBMP-2/ACS enhances regeneration of missing bone and osseointegration of dental implants subject to functional loading. MATERIALS AND METHODS: Two bilateral standardized large saddle-type defects (≈10 × 10 × 6 mm) were surgically created in each mandible of seven beagle dogs 2 months after tooth extraction. Defects were immediately reconstructed randomly using rhBMP-2 (O-BMP or InFuse) soaked in ACS, deproteinized bovine bone mineral (DBBM) granules, or ACS alone as surgical control and subsequently covered with collagen membrane. Screw-type sand-blasted, acid-etched dental implants were placed 3 months later into the reconstructed defects and into adjacent bone. Osseointegration was allowed to progress for 3 months before functional loading of 3 months until sacrifice. RESULTS: Significantly more bone fill was radiographically observed for GBR with rhBMP-2/ACS (O-BMP: 92.5%, InFuse: 79%) in comparison to the DBBM (52%) and ACS alone groups (56.6%). Osseointegration was achieved and maintained in all experimental defects challenged by prostheses-driven functional load. The bone density ranged from 37.49% in the ACS group to 64.9% in the rhBMP-2/ACS (InFuse) group with no significance. The highest mean percentage of BIC was found in rhBMP-2/ACS (InFuse: 52.98%) with no statistical difference. Crestal bone resorption was observed around implants placed in reconstructed areas without any significant difference. CONCLUSION: GBR with rhBMP-2/ACS provided the greatest bone fill among the three treatment procedures. GBR with rhBMP-2/ACS showed efficacy for placement, osseointegration, and functional loading of titanium implants in alveolar ridge defects.

Periodontal and endodontic pathology delays extraction socket healing in a canine model.

PURPOSE: The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. METHODS: The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. RESULTS: During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. CONCLUSIONS: Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket healing.

Is ridge preservation/augmentation at periodontally compromised extraction sockets safe? A retrospective study.

OBJECTIVES: This study aimed to evaluate the safety of ridge preservation/augmentation procedures when performed at compromised extraction sockets. METHODS: Patients subject to ridge preservation/augmentation at periodontally compromised sockets at Seoul National University Dental Hospital (SNUDH) were evaluated in a chart review. Tooth extractions due to acute infection were not included in our study as chronically formed lesions are the only lesions that can be detected from radiographic images. If inflammatory symptoms persisted following ridge preservation/augmentation and antimicrobial and anti-inflammatory therapy, the patient was categorized as a re-infection case and implanted biomaterial removed. RESULTS: Of 10,060 patients subject to tooth extractions at SNUDH, 2011 through 2015, 297 cases meeting inclusion criteria were reviewed. The severity and type of lesions were not specific because extracting data was only done by radiographic images and chart records. The review identified eight patients exhibiting inflammatory symptoms that required additional antimicrobial and anti-inflammatory therapy. Within this group, re-infection occurred in two patients requiring biomaterials removal. The final safety rate for the ridge preservation/augmentation was 99.3%. None of the demographic factors, systemic conditions or choice of biomaterial affected the safety of ridge preservation/augmentation. CONCLUSION: Alveolar ridge preservation/augmentation at periodontally compromised sockets appears safe following thorough removal of infectious source.

In Vivo Inhibition of Porphyromonas gingivalis Growth and Prevention of Periodontitis With Quorum-Sensing Inhibitors.

BACKGROUND: Autoinducer (AI)-2 has an important role in biofilm formation in the oral environment. Mature biofilms formed as a result of the cell-to-cell communication make it difficult to overcome periodontitis with the use of antibiotics. Previous in vitro studies suggest that quorum-sensing inhibitors (QSIs) interfere with AI-2. This study compares the QSI effects resulting from an oral inoculation of Porphyromonas gingivalis in an experimental animal model. METHODS: Forty-five male mice were divided into three groups (n = 15 each): 1) infection; 2) QSI; and 3) control. Infection and QSI groups received oral inoculation of P. gingivalis, whereas treatment with QSIs (furane compound and d-ribose) was only performed in the QSIs group. The control group was a negative control not receiving manipulation. After 42 days, mice were sacrificed, and the distance from the alveolar bone crest (ABC) to the cemento-enamel junction (CEJ) was measured by microcomputed tomography. P. gingivalis DNA was quantified in the soft and hard tissues around the molar teeth by real-time polymerase chain reaction. RESULTS: Distance from ABC to CEJ was significantly increased in the P. gingivalis infection group compared with the control group (P = 0.02) and significantly decreased in the QSI group compared with the infection group (P = 0.02). The QSI group contained 31.64% of the bacterial DNA count of the infection group. CONCLUSION: Use of QSIs in the mice infection model showed a reduction of bone breakdown and a decrease in the number of bacteria in vivo, suggesting that QSIs can be a new approach to prevention and treatment of periodontitis.

Hyaluronic Acid Improves Bone Formation in Extraction Sockets With Chronic Pathology: A Pilot Study in Dogs.

BACKGROUND: Previous studies on ridge preservation focusing on fresh extraction sockets using graft materials for ridge preservation procedures have reported a delay in the tissue modeling and remodeling phases. The objective of this study is to evaluate the effect of hyaluronic acid (HA) on healing of infected sockets. METHODS: Six beagle dogs were used in this study. Both mandibular third premolars were hemisected, and the distal roots were extracted. Subsequently, periodontal and endodontic lesions were induced at the remaining mesial root. After communication of the periodontal lesion, an endodontic periapical lesion was observed at 4 months, and the mesial roots of both the right and left sides were extracted. HA was applied into the socket of the test group, and no treatment was administered to the other group (control group). Three months after extraction of the mesial roots, the dogs were sacrificed, and histologic evaluations were performed. RESULTS: The sockets were filled by mineralized bone (47.80% ± 6.60%) and bone marrow (50.47% ± 6.38%) in the control group, whereas corresponding values were 63.29% ± 9.78% and 34.73% ± 8.97% for the test group, respectively. There was a statistically significant difference between the groups. Reversal lines and a copious lineup of osteoblasts were observed in the middle and apical parts of the sockets in the test group. CONCLUSION: An infected socket shows delayed healing of the socket wound, and HA, because of its osteoinductive, bacteriostatic, and anti-inflammatory properties, may improve bone formation and accelerate wound healing in infected sockets.