pdgf与种植体黏膜炎

Background: Osseointegrated dental implants have become increasingly common as a treatment option for missing teeth. Peri-implant infections are caused by bacterial plaque that may initiate an inflammatory release of cytokines, enhance accumulation of neutrophils in implant lesion, and trigger the production of matrix metalloproteinase-8 (MMP-8). MMP-8 is essential in inflammatory and degenerative processes of periodontal tissues and produced by activated cells. The purpose of this study was to detect the role of MMP-8 as a biomarker of active and aggressive peri-implant mucositis. Material and method: Eighty subjects (40 with peri-implant mucositis and 40 with successful and healthy peri-implant mucosa) were enrolled in this study. The 42 male and 38 female subjects were attended at AL-Karama and AL-Ma'amoun Specialized Dental Centers in Baghdad, Iraq from November 24, 2021 to May 25, 2022. Follow-up examinations were performed on patients to monitor the progression of disease. Peri-implant sulcular fluid was examined and identified using enzyme-linked immunosorbent assay technique for MMP-8. Results: Results showed that MMP-8 levels continue to rise after 3 weeks and are significantly higher in the patient group (P=0.00000) than the group with successful implants. Conclusion: MMP-8 can be used to reflect, associate, and predict clinical disease activity and progression of peri-implant mucositis properly.

OBJECTIVES To clinically and histologically evaluate the efficacy of using acellular dermal matrix (ADM) for peri-implant vertical soft tissue augmentation at implant placement. MATERIALS AND METHODS Twenty patients were enrolled in this study. According to the initial thickness of vertical soft tissue, patients were assigned into the ADM group (≤2 mm) or the control group (>2 mm) prior to implant surgery + ADM grafting or implant surgery alone. Second-stage surgery was carried out 3 months later and a small piece of ridge membrane was harvested for histological and immunohistochemical evaluation. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in peri-implant crevicular fluid (PICF) were also assessed 1 week, 1 month and 5 months after second-stage surgery. Clinical parameters were recorded to evaluate peri-implant health at 1 week and 3 months after implant restoration. RESULTS All 20 implants healed uneventfully and successfully. Soft tissue thicknesses were comparable in the two groups at second-stage surgery (3.20 ± 0.42 mm vs 3.50 ± 0.58 mm). In the ADM group, the mean increase in soft tissue thickness was 1.85 ± 0.34 mm. Histological and immunohistochemical outcomes showed no differences between the two groups. VEGF and PDGF-BB levels in PICF were significantly lower in the ADM group 1 week after second-stage surgery (p < 0.01), yet they decreased in both groups later. The difference between the groups had disappeared by 5 months after second-stage surgery. The clinical peri-implant parameters were good and stable by the end of the study (3 months after restoration). CONCLUSIONS Our results suggested that using ADM at implant placement was effective in increasing the thickness of peri-implant vertical soft tissue and achieved comparable clinical and histological performance to the control group. However, the incremental soft tissue showed inferior angiogenic ability in the early stage of wound healing.

While osseointegration has traditionally been the focal point of dental implant design, recent research highlights the equally crucial role of establishing a resilient and biologically integrated soft tissue seal for long-term implant success. This review critically examines recent advances (primarily from the past five years) that elucidate the molecular, cellular, and materials science strategies essential for enhancing peri-implant soft tissue integration. Key factors include precisely engineered surface topographies at micro- and nanoscale levels, surface chemical modifications that enhance wettability and protein adsorption, and biomimetic coatings incorporating extracellular matrix-derived peptides, chemokines, and growth factors. Recent studies underscore the impact of laser micro- and nano-texturing, plasma treatments, and biofunctionalization in modulating fibroblast and epithelial cell behaviors, accelerating tissue attachment, and mitigating early inflammatory responses. Emerging implant-abutment designs, such as platform switching and transmucosal zirconia abutments, demonstrate improved soft tissue stability and reduce crestal bone loss. Additionally, the immunomodulatory potential of next-generation materials offers promising avenues for directing macrophage polarization and enhancing wound resolution. Collectively, this review synthesizes the latest evidence on material-driven and biological strategies for engineering a stable soft tissue interface. It provides a translational roadmap for the development of implant systems optimized for long-term soft tissue health, addressing a critical unmet need in dental implantology.

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Bacterial invasion at the titanium-tissue interface causes peri-implant inflammation, posing challenges for implants in orthopedics, maxillofacial prosthetics, and dentistry. This study hypothesized that titanium surface decarbonization improves soft tissue cell adhesion and growth. One-minute vacuum ultraviolet (VUV) light treatment at 172 nm reduced surface carbon from 60% to 29% without altering surface topography, making surfaces hydrophilic and hydro-attractive. Human fibroblasts attached to VUV-treated surfaces 2-4 times more frequently than untreated surfaces, with an even greater increase on tilted and curved surfaces. Fibroblast proliferation rose 2-6 times, with an expedited G1-to-S phase transition. Cell retention under dislodging forces increased 2-5 times on VUV-treated surfaces. RNA sequencing showed upregulation of extracellular matrix production, growth factors, cell cycle progression, antioxidant defenses, and proteoglycan/glycosaminoglycan (GAG)-binding, alongside downregulation of the inflammatory response on VUV-treated titanium surfaces. An oxidative stress test showed minimal adverse effects from hydrogen peroxide on cells on VUV-treated surfaces, attributed to increased intracellular glutathione reserves. Enhanced adhesion on VUV-treated titanium was negated by treating the cells with GAG-cleaving enzymes. These findings demonstrate that VUV-mediated decarbonization enhances fibroblast attachment, proliferation, and adhesion by fostering homeostatic cellular phenotypes involving proteoglycan/GAG interactions and antioxidant defense, offering a strategy to improve the soft tissue sealing around titanium implants.

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Soft tissue sealing around zirconia (ZrO2) abutment is critical for the long-term stability of dental implants. The goal of the study is to develop a strong basal lamina (BL)-mediated epithelial attachment to ZrO2 via a novel physicochemical immobilization method. An electrophoretic fusion (EPF) method was applied to fuse a phosphonic acid (PA) linker to ZrO2 discs. Bindings of the PA linker and the following protease activated receptor 4 (PAR4) were verified by Fourier-transform infrared spectroscopy (FITR). Then, ZrO2 discs were doped in platelet-rich plasma (PRP). Platelet-derived growth factor (PDGF) was measured to assess platelet activation. PRP-doped discs were subsequently co-cultured with human gingival epithelial cells (OBA9) to evaluate establishment of basal lamina-mediated epithelial attachment. The EPF method achieved robust immobilization of the PA linker and PAR4 onto the ZrO2 surface. The resultant PAR4-coupled ZrO2 successfully induced platelet aggregation and activation. Furthermore, a BL-mediated epithelial attachment was established. The results are significant for clinical application to minimize the risk of developing peri-implant diseases.

The primary aim of this cross‐sectional study was to investigate the association between prosthesis design and peri‐implant mucosa dimensions and morphology. The secondary aim was to investigate associations between mucosal dimensions and the presence of mucositis.

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Summary Dental implants make it possible to replace teeth in more sophisticated ways. Nevertheless, peri-implantitis is one of the leading causes of implant failure, which can be avoided with proper soft tissue sealing. The aim of this study was to achieve the promotion of the synthesis of peri-implant epithelial hemidesmosome through Histatin 1 and porcine small intestinal submucosa (SIS) hydrogel to form a good peri-implant seal. The results show that hydrogel can improve the biological barrier function around implants by combining antibacterial, promoting soft tissue healing and promoting epithelial bonding. This means that the morphology and anti-infection ability of soft tissue are enhanced, which ensures the long-term stability of the implant.SIS-Hst1 hydrogel has certain clinical application in the prevention and early treatment of peri-implantitis. In conclusion, Hst1-SIS hydrogel, as a local administration system, provides experimental evidence for the prevention of peri-implant disease.

ABSTRACT Objectives The purpose of this pilot study is to compare gene expression in mucosa around dental implants with zirconia abutment to titanium and investigate presence of particles in mucosa samples and on implant heads. Material and Methods Ten patients with a single implant supported prosthesis connected to zirconia or titanium abutments were invited at the five-year control. A clinical examination and a survey on experience of function and appearance were conducted. A mucosa biopsy taken in close vicinity to the implant were analysed by real-time polymerase chain reaction (qPCR) and presence of particles in a scanning electron microscope/energy-dispersive X-ray spectroscope (SEM/EDX). Cytological smear samples were collected and analysed through inductively coupled plasma mass spectrometry (ICP-MS) to investigate presence of particles on implant heads. Results In total, 9 patients participated in the study, five with titanium abutments and four with zirconia abutments. All patients were satisfied with function and aesthetics. Titanium and iron particles were detected in mucosa biopsies. The ICP - MS analysis demonstrated presence of zirconia and titanium. Several proinflammatory genes were upregulated in the zirconia abutment group. Conclusions Around zirconia abutments a slight increase in proinflammatory response and amount of wear particles was seen as compared to titanium. Wear particles of titanium were present in all soft tissue samples, however zirconia particles only in the samples from implants heads/mucosa with zirconia abutments.

The stability of peri-implant soft tissues is essential for long-term success. Integrins play a vital role in biological processes through developing and maintaining cell interactions; however, few studies have evaluated the effects of modifications to abutment surfaces on cell adhesion across integrin expression. Therefore, this pilot study assessed the influence of different surface topographies of titanium healing abutments prepared by additive manufacturing (AM) on the gene expression levels of the integrin subunits α2, β1, αv, and β6 in the human peri-implant mucosa. Thirteen healthy adults were included. Depending on the number of required implants, the subjects were distributed in different groups as a function of healing abutment topography: group 1 (fully rough surface); group 2 (upper machined + lower rough); group 3 (rough upper surface + lower machined); group 4 (fully machined). A total of 40 samples (n = 10/group) of the peri-implant mucosa around the abutments were collected 30 days after implant placement, and subsequently, the gene expression levels were evaluated using real-time PCR. The levels of gene expression of β1-subunit integrin were upregulated for individuals receiving fully rough surface abutments compared with the other surface topographies (p < 0.05). However, the healing abutment topography did not affect the gene expression levels of the α2, αv, and β6 integrin subunits in the human peri-implant mucosa (p > 0.05). This preliminary study suggested that controlled modifications of the surface topography of titanium healing abutments produced by AM may influence the quality of the peri-implant mucosa in the early stages of the soft tissue healing process.

Aim and objectives: The aim of the present study is to detect the presence of changes in the color of the peri-implant mucous membranes in a group of patients with implants supported dentures and to correlate these changes with the age of the dentures. Our study group consisted of 62 patients with one or more dental implants placed between 6 months and 5 years prior to the study. Data were collected by dental examinations and were photographically documented. Later, the data were introduced and analyzed in SPSS software, version 14.0. The correlations revealed that all patients with peri-implant mucosal discoloration had prosthesis placed in the previous 2 years. If these color changes are not a sign of peri-implant inflammation, we recommend evaluating them regularly to follow their evolution.

Background: An experimental study was designed to evaluate the effect of chlorhexidine gluconate chips on clinical status of peri-implant mucosa and plaque formation on healing abutments following single-stage implant surgeries. Materials and Methods: Twenty-eight single-stage implant sites were grouped into 14 test and control sites. The study commences from the time of suture removal following surgery, designated as day 0. Chlorhexidine chip insertion into peri-implant sulcus in test sites was done on day 0, 10, and 20. Peri-implant crevicular fluid was collected on day 0, 10, 20, and 30 for biochemical estimation of aspartate aminotransferase (AST). The modified sulcus bleeding index (mBI) score was obtained in both test and control sites on day 10, 20, and 30. On day 30, all the healing abutments were unscrewed and sent for stereomicroscopic analysis to assess the plaque formation on its surface. Results: Statistically significant difference was not observed in AST levels and mBI in both test and control groups in various time intervals. In the stereomicroscopic assessment of healing abutment, mild grade of plaque accumulation was seen in three samples in test group, one sample in control group, and severe grade was seen in six samples in test group and nine samples in the control group. Conclusion: Inflammatory condition of peri-implant mucosa and plaque retentive properties on healing abutment surface were found to have reduced with the usage of chlorhexidine gluconate chips. However, the study failed to establish a statistically significant correlation of these observations.

The morphology and histology of the soft tissue around the implant are different from the periodontal tissue, but the difference in the regulation of blood flow is not known. The aim of the study was to compare the resting blood flow and the vasodilatation capacity of the gingiva between implants and teeth. Twenty-six healthy volunteers with single-tooth implants were involved. The implant-borne crown was retained on either a zirconia or titanium abutment. The vasodilatation capacity of the gingiva was assessed by a postocclusive reactive hyperemia test. Blood flow was measured by a laser speckle contrast imager at the buccal gingiva of the implant-borne crown and an analog natural tooth. No significant differences in baseline gingival blood flow were observed between the different abutments and the teeth in either region. The hyperemia after compression was significantly attenuated at the zirconia abutments in all regions during the entire investigation period (20 minutes) compared to the titanium abutments and the teeth. No differences were observed between titanium abutments and the teeth. The resting microcirculation seems to be the same at implants and teeth. However, the vascular reactivity might be disturbed at the zirconia, but not at the titanium, abutment.

Background: Peri-implant diseases leading to the failure of dental implants is concern in the field of dentistry. Difference in immune response around peri-implant tissues with healthy tissue might be responsible for the hidden cause of peri-implant diseases. Hence, in the current study, the dispersion of the dendritic cell (DC) subpopulations and Langerhans cells (LCs) was evaluated in healthy peri-implant mucosa (HPIM) and healthy mucosa (HM) to know the imbalance in immune homeostasis. Subjects and Methods: A total of 15 nonsmoker participants were selected for the study. First sample of the HM was obtained before the implant placement (Group I) and second sample of peri-implant mucosa was obtained at the time of placement of the gingival former (Group II). Immunochemistry was used to quantify DCs and LCs in the samples. Statistical Analysis Used: To analyze the distribution of cells in the epithelium and lamina propria, Wilcoxon matched pairs test was used. Results: Mean numbers of CD1a (LCs) in the epithelium and lamina propria of Group I and Group II were 25.2 ± 6.41 and 27.47 ± 10.26 and 19.27 ± 7.27 and 12.46 ± 3.04, respectively. Mean numbers of factor XIIIa (DCs) in the epithelium and lamina propria in Group I and Group II were 30.37 ± 5.42 and 86.93 ± 13.99 and 50.47 ± 7.27 and 124.33 ± 10.27, respectively. Statistically significant differences in the number of cells in the epithelium and lamina propria of Group I and Group II were noted (P = 0.001 and P = 0.001). Conclusions: CD1a-positive LCs were more in the epithelium rather than lamina propria in Group II. Higher numbers of factor XIIIa-positive DCs were observed in the lamina propria than epithelium in Group I and II.

The poor quality of life associated with the loss of teeth can be improved by the placing of dental implants. However, successful implantation relies on integration with soft tissues or peri-implant inflammatory disease that can lead to the loss of the implant. Pharmacological agents, such as antibiotics and antiseptics, can be used as adjunct therapies to facilitate osseointegration; however, they can have a detrimental effect on cells, and resistance is an issue. Alternative treatments are needed. Hence, this study aimed to examine the safety profile of bergenin (at 2.5 μM and 5 μM), a traditional medicine, towards human gingival fibroblasts cultured on acid-etched zirconia implant surfaces. Cellular responses were analysed using SEM, resazurin assay, and scratch wound healing assay. Qualitative assessment was conducted for morphology (day 1) and attachment (early and delayed), and quantitative evaluation for proliferation (day 1, 3, 5 and 7), and migration (0 h, 6 h and 24 h). The concentrations of bergenin at 2.5 μM and 5 μM did not demonstrate a statistically significant effect with regard to any of the cellular responses (p > 0.05) tested. In conclusion, bergenin is non-cytotoxic and is potentially safe to be used as a local pharmacological agent for the management of peri-implant inflammatory diseases.

PURPOSE The maintenance of peri-implant health relies significantly on the integrity of the peri-implant seal, particularly vulnerable at the interface between implant abutment and soft tissue. Early healing stages around implants involve cellular exposure to oxidative stress. This study aimed to investigate whether vacuum ultraviolet (VUV)-treated titanium augments the growth and functionality of human gingival fibroblasts while mitigating cellular stress. METHODS Machined titanium plates underwent treatment with 172 nm VUV light for one minute, with untreated plates as controls. Human gingival fibroblasts were cultured on treated and untreated plates, and their behavior, growth, and functionality were assessed. Functionally impaired fibroblasts, treated with hydrogen peroxide, were also cultured on these titanium plates, and plate-to-plate transmigration ability was evaluated. RESULTS Fibroblasts on VUV-treated titanium exhibited a 50% reduction in intracellular reactive oxygen species production compared to controls. Additionally, glutathione, an antioxidant, remained undepleted in cells on VUV-treated titanium. Furthermore, the expression levels of inflammatory cytokines IL-1β and IL-8 decreased by 40-60% on VUV-treated titanium. Consequently, fibroblast attachment and proliferation doubled on VUV-treated titanium compared to those in the controls, leading to enhanced cell retention. Plate-to-plate transmigration assays demonstrated that fibroblasts migrated twice as far on VUV-treated surfaces compared to those in the controls. In particular, the transmigration ability, impaired in functionally impaired fibroblasts on the controls, was preserved on VUV-treated titanium. CONCLUSIONS VUV-treated titanium promotes the growth, function, and migration of human gingival fibroblasts by reducing cellular stress and enhancing antioxidative capacity. Notably, the transmigration ability significantly improved on VUV-treated titanium.

ABSTRACT Background: Peri-implant soft tissue health is crucial for the long-term success of dental implants. Patients with systemic conditions, such as diabetes mellitus and cardiovascular diseases, are at higher risk for peri-implant complications. This study aimed to assess the cellular responses of peri-implant soft tissues in vitro, simulating conditions influenced by systemic diseases, to better understand the potential impact of these conditions on implant success. Materials and Methods: An in vitro study was conducted using human gingival fibroblasts exposed to simulated inflammatory conditions representative of diabetes (high glucose environment) and cardiovascular diseases (increased proinflammatory cytokines). Titanium discs with treated surfaces were used to mimic implant surfaces. Cellular proliferation, adhesion, and cytokine expression were evaluated using MTT assay, fluorescence microscopy, and ELISA, respectively. Experimental groups included Group 1: Healthy control, Group 2: High-glucose condition, Group 3: Proinflammatory cytokine condition, and Group 4: Combined high-glucose and proinflammatory cytokine condition. Results: Fibroblast proliferation rates were significantly reduced in Groups 2 (50%) and 3 (55%) compared to Group 1 (85%). Adhesion strength was also compromised in Groups 2 (60%) and 3 (65%), with the lowest observed in Group 4 (40%). Cytokine analysis revealed elevated levels of IL-6 and TNF-α in Groups 3 (IL-6: 150 pg/mL, TNF-α: 200 pg/mL) and 4 (IL-6: 180 pg/mL, TNF-a: 250 pg/mL) compared to the control (IL-6: 50 pg/mL, TNF-α: 60 pg/mL). Conclusion: Systemic conditions significantly impair peri-implant soft tissue cellular responses, including proliferation, adhesion, and inflammation regulation. These findings underscore the importance of tailored peri-implant management strategies for patients with systemic diseases to ensure implant longevity.

Objectives: This study aimed to evaluate the effects of different titanium (Ti) anodized surfaces on soft tissue healing around dental implant abutments. Methods: Discs of machined (MC), pink anodized (PA) and yellow anodized (YA) surfaces were morphologically characterized and evaluated in vitro. Cell adhesion and collagen synthesis by human gingival fibroblasts (hGFs) were assessed to evaluate the regenerative potential of the surfaces under study. Their inflammatory potential was evaluated in THP-1 cell cultures by measuring cytokine secretion, and their proteomic adsorption patterns were characterized using nano-liquid chromatography mass spectrometry (nLC-MS/MS). Statistical significance was considered at 5%. In relation to proteomics, statistical differences were evaluated using the Student t-test with the Perseus application. Results: The anodization process resulted in a reduction in the surface roughness parameter (Ra) relative to the machined titanium (p < 0.05). No differences in hGF adhesion were found between the surfaces after one day. PA induced increased hGF collagen synthesis after 7 days (p < 0.05). The secretion of TNF-α was lower for anodized surfaces than for MC, and its concentration was lower for PA than for YA (p < 0.05). In turn, TGF-β was higher for PA and YA versus MC after one and three days of culture. A total of 176 distinct proteins were identified and 26 showed differences in adhesion between the anodized surfaces and MC. These differential proteins were related to coagulation, lipid metabolism, transport activity, plasminogen activation and a reduction in the immune response. Conclusions: Anodized Ti surfaces showed promising anti-inflammatory and regenerative potential for use in dental implant abutments. Anodization reduced surface roughness, increased collagen synthesis and lowered TNF-α secretion while increasing TGF-β levels compared to machined surfaces. Identified proteins related to coagulation and lipid metabolism supported these findings. Clinical relevance: Anodized surfaces could offer improved short-term peri-implant soft tissue healing over machined surfaces. The analysis of abutment surface, instead of implant surface, is a new approach that can provide valuable information.

Abstract Objective: Aim of present study was to evaluate gingival tissue samples obtained from healthy and diseased sites of teeth and dental implants in terms of hypoxia and collagenase activity. Methods: Four study groups were created as Group-1; healthy individuals (H), Group-2; periodontitis patients with stage 3 grade B (P), Group-3; patients with peri-implant mucositis. Group-4; patients with peri-implantitis (P-IMP). Plaque index (PI), gingival index (GI) and probing pocket depth (PPD) were recorded. Gingival and peri-implant mucosal biopsies were obtained. Fibroblast and inflammatory cells were counted. Hypoxia-inducible factor (HIF)-1α, prolyl hydroxylase (PH), matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) levels were determined via immunohistochemistry. Results: Healthy controls had highest fibroblast cell counts and lowest inflammatory cell counts compared to other groups. Peri-implantitis and periodontitis samples had similar fibroblast and inflammatory cell counts, while peri-implant mucositis had higher fibroblast cells and lowered inflammatory cells compared to periodontitis and peri-implantitis samples. HIF-1α, COX-2 and iNOS levels were lowest in healthy controls and increased in other groups. Peri-implant mucositis samples had significantly lower expressions of HIF-1α, COX-2 and iNOS compared to peri-implantitis and periodontitis groups. PH expressions were lower in periodontitis and peri-implantitis groups compared to healthy controls and peri-implant mucositis groups. MMP-8 levels were lower in healthy group compared to other groups while levels were similar in periodontitis, peri-implant mucositis and peri-implantitis groups. TIMP levels were similar in groups. Conclusion: Periodontitis, peri-implantitis, and peri-implant mucositis samples exhibited higher inflammation and lower fibroblast cell counts and tend to have increased tissue collagenase activity, hypoxia and inflammation compared to healthy samples.

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Dental implant clinical success is dependent on effective peri-implant tissue attachment to the trans-mucosal portion following placement. Modification of transmucosal implant surfaces can improve cellular adhesion and function leading to formation of an effective soft-tissue seal during healing, of which gingival fibroblasts are prominent cells to migrate to repair wounds and crucial for the development of a collagen rich connective tissue. Biocompatible loaded scaffold materials have been developed to allow local release of molecules with effective biological activity. Our previous studies indicate that strontium can promote gingival fibroblast metabolism, decrease apoptosis and support adhesion to titanium healing abutments. In this study, we developed a strontium-loaded alginate hydrogel scaffold which can be easily personalized to fit over any size and shape of implant transmucosal collar or healing abutment. Results indicate that biologically active strontium ions are effectively released from loaded alginate hydrogel material to promote fibroblast viability and migration to repair in vitro wounds similar to that of strontium citrate solution. Overall, this novel strontium-loaded alginate scaffold device displays good biocompatibility and functionality, demonstrating high potential as a system to provide local delivery of strontium to improve peri-implant mucosal healing following implant placement and clinical success.

Purpose: To investigate inflammatory responses in peri-implant crevicular fluid (PICF) in comparison to periodontal tissue. Materials and Methods: Nineteen participants with healthy implants restored with titanium or gold-casting abutment were included. PICF and gingival crevicular fluid (GCF) were collected for inflammatory cytokine detection by ELISA. Cytokine levels in PICF or GCF of the same individual were compared using the paired t-test, and those from titanium or gold-casting (UCLA) abutment were compared using the independent t-test. Human gingival fibroblast responses to PICF and GCF were then evaluated with one-way ANOVA. Results: The results demonstrated that IL-6, IL-8, TNFα, and IFNγ expressed in PICF are similar to GCF in the same individual. However, IL-1β (p = 0.032) and IL-1α (p = 0.030) was statistically significantly higher in PICF than in GCF. IL-8 level was statistically significantly higher with gold-casting than with titanium abutments (p = 0.003). PICF statistically significantly stimulated higher expression of RANKL, IL-1β, IL-6, and IL-8 mRNA in human gingival fibroblasts (HGF), while focal adhesion kinase (FAK) suppressed mRNA. Conclusion: The inflammatory cytokines, including IL-1α and IL-1β, are higher in healthy peri-implant tissues. Abutment materials may also influence the level of inflammatory cytokines in PICF. Inflammatory mediators in crevicular fluid may affect HGF inflammatory responses and peri-implant tissue integration.

Introduction: The objective of this study was to examine the effect of photofunctionalization on the soft-tissue contour formed at the interface of various abutment materials using end-point analyses obtained from the three-dimensional oral mucosal model (3D-OMMs). Methods: Commercially pure titanium (CPTi), alumina-toughened zirconia (ATZ), and yttria-stabilized zirconia (YSZ) made into discs shapes were classified into two groups: UV-treated (PTx) and non-treated (NTx). The materials in PTx groups were exposed to UV light for 12 min. Human gingival fibroblasts and TR146 epithelial cell lines co-cultured on the acellular dermal membrane were used to construct the 3D-OMM. After 4 days of culture, the discs were inserted into the holes prepared within the membrane of 3D-OMMs. The contour formed by the tissue was evaluated after 14 days of culture. Results: The UV treatment of abutment materials resulted in the formation of more non-pocket-tissue types among the PTx group (p = 0.002). Of all materials tested, soft tissue contour around YSZ showed higher scores for the non-pocket type in both non- and UV-treated groups. Conclusions: The non-pocket type of tissue attachment was frequently found in all surfaces modified by photofunctionalization, particularly zirconia. The 3D-OMM can be used to evaluate the biological endpoints of implant surface modifications.

Soft tissue integration (STI) at the transmucosal level around dental implants is crucial for the long-term success of dental implants. Surface modification of titanium dental implants could be an effective way to enhance peri-implant STI. The present study aimed to investigate the effect of bioinspired lithium (Li)-doped Ti surface on the behaviour of human gingival fibroblasts (HGFs) and oral biofilm in vitro. HGFs were cultured on various Ti surfaces—Li-doped Ti (Li_Ti), NaOH_Ti and micro-rough Ti (Control_Ti)—and were evaluated for viability, adhesion, extracellular matrix protein expression and cytokine secretion. Furthermore, single species bacteria (Staphylococcus aureus) and multi-species oral biofilms from saliva were cultured on each surface and assessed for viability and metabolic activity. The results show that both Li_Ti and NaOH_Ti significantly increased the proliferation of HGFs compared to the control. Fibroblast growth factor-2 (FGF-2) mRNA levels were significantly increased on Li_Ti and NaOH_Ti at day 7. Moreover, Li_Ti upregulated COL-I and fibronectin gene expression compared to the NaOH_Ti. A significant decrease in bacterial metabolic activity was detected for both the Li_Ti and NaOH_Ti surfaces. Together, these results suggest that bioinspired Li-doped Ti promotes HGF bioactivity while suppressing bacterial adhesion and growth. This is of clinical importance regarding STI improvement during the maintenance phase of the dental implant treatment.

Background Natural compounds and biomaterials, such as nanohydrogels, have gained interest due to their biocompatibility and tissue regeneration potential. A novel nanohydrogel was prepared by employing Tridax procumbens, a traditional plant with anti-inflammatory properties and chitosan nanoparticles and a natural bioadhesive with potent antimicrobial and antioxidant effects and dopamine, which has been shown to regulate angiogenesis and influence cell growth. The objective of this study was to examine how human gingival fibroblast (HGF) cells respond to a nanohydrogel formulation containing dopamine, chitosan nanoparticles, and T. procumbens extract in terms of cell viability and cell migration. Methods From human gingival tissue, fibroblasts were cultured. A nanohydrogel formulation was prepared by combining dopamine, chitosan nanoparticles, and T. procumbens extract. Three groups were evaluated: Group 1 (nanohydrogel containing dopamine, chitosan nanoparticles, and T. procumbens extract (DnCTP)), Group 2 (chitosan nanoparticles and T. procumbens extract (nCTP)), and Group 3(T. procumbens extract (TP)). The MTT assay was used to measure the percentage of cell viability and a scratch assay to observe cell migration in the wounded area at different concentrations. The data were tabulated in Microsoft Excel (Microsoft Corporation, USA) and imported to IBM SPSS Statistics for Windows, version 23.0 (released 2015, IBM Corp., Armonk, NY), and the Mann-Whitney U test was conducted to statistically analyze the cell viability for different concentrations within the three groups. Results The nanohydrogel formulation (DnCTP) showed dose-dependent effects on cell viability with the highest cell viability at 40 µL/mL concentration, and higher concentrations of 80 µL/mL exhibited cytotoxic effects. nCTP and TP showed decreased cell viability at 80 µL/mL concentration (p < 0.05), indicating potential cytotoxicity at higher concentrations. DnCTP showed improved cell migration in the scratch assay as compared to other groups (nCTP and TP), indicating its potential for facilitating wound healing. Conclusion Dopamine, chitosan nanoparticles, and T. procumbens worked together synergistically to create a nanohydrogel formulation (DnCTP) that showed promise for improving wound healing in human gingival fibroblast cells at a dose-dependent concentration, which may therefore work as an excellent wound-healing agent in periodontal and peri-implant therapy.

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens—bis-acrylic 1 and 2, flowable and bulk–fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control—were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20–30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk–fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.

Peri-implant health depends on the complex interactions between the dental implant, surrounding soft/hard tissues and the oral microbial environment. However, existing 2D and monoculture models fail to replicate this complexity, limiting their clinical relevance. Therefore, this study aimed to develop a clinically relevant 3D in vitro model that integrates oral soft tissue, hard tissue and a titanium implant in a 3D setup to accurately replicate the peri-implant environment. In addition, the model was designed to integrate bacterial biofilms, in order to mimic incipient peri-implant infections. As a hard tissue component, osteoblast-covered HA/TCP scaffold structures were developed and merged with peri-implant mucosa, resulting in a 3D in vitro peri-implant bone-mucosa composite model. The composite model was then cultivated for 2, 7 and 14 days. At each time point, histological analysis, live/dead staining and collagen immunofluorescence staining were performed to assess its structural integrity, osteoblast viability and bone ECM characteristics. To demonstrate proof-of-concept for suitability in simulating implant infection, an oral multispecies biofilm was integrated on top of the implant in the peri-implant bone-mucosa model. Cell viability and osteoblastic phenotype were maintained throughout the study period. Microscopic and histological analyses confirmed a homogenous structure, with a stratified epithelium overlying collagen-embedded human gingival fibroblasts closely connected to the underlying scaffold structure interspersed with bone cells. Combined with a living multispecies biofilm, this model represents several essential components observed in peri-implant interaction. By combining oral soft tissue, hard tissue and a titanium implant in a 3D setup, this model represents the first and most complex model for evaluating innovative implant materials and novel treatment strategies as well as studying the development of peri-implant diseases. Incorporating different biofilms could enhance the model’s clinical relevance, enabling the study of pro-inflammatory responses to bacterial infections in a setting that includes both soft and hard tissue.

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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.

AIM To evaluate the cytokine, chemokine, and growth factor levels in peri-implant sulcular fluid (PISF) during healing and osseointegration at osteotomy sites prepared either with piezosurgery (PS) or drills. METHODS Fourteen patients having contralateral partial edentulism in the posterior maxilla were enrolled and 38 osteotomies were prepared. Implants were placed with one-stage surgery. Insertion torque, early healing index, probing depth and modified gingival and plaque indices and crestal bone loss (CBL) were measured. PISF was collected from each implant at weeks 2, 4, 8, 12, and 24 and were analyzed by a 30-Plex immunoassay. Data analysis employed Brunner-Langer method. RESULTS CBL values did not depend on osteotomy modality (P > 0.05). Eighteen molecules (interleukine (IL)-1β, granulocyte colony stimulating factor (G.CSF), IL-13, IL-6, IL-12, interferon (IFN)-γ, IFN-α, IL-2, IL-2 R, IL-8, macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-1, interferon gamma-induced protein (IP)-10, monokine induced by IFN-γ (MIG), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) showed time-dependent decrease (P < 0.05), but they were not treatment-dependent (P > 0.05). When values of weeks 4, 8, 12, and 24 were compared to week 2, it was found that all were highest at week 2 and decreased thereafter (P < 0.05). The decrease was significant at weeks 4 or 8 for multitude of molecules and was mostly sustained throughout the follow-up. Week 8 regulated on activation, normal T cell expressed and secreted (RANTES) values in PS group were lower in PS group compared to drill group (P < 0.05). CONCLUSION Implants placed into osteotomies created with PS and drills are similar in terms of PISF biomarker changes during the osseointegration and wound healing period. When clinical and CBL parameters were taken into account together with the PISF molecular data it can be speculated that PS and conventional drill osteotomy have similar effects on peri-implant tissues on the biochemical, clinical and radiological levels.

BACKGROUND A biological seal that protects the implant from any biological or external impingement is created by the supracrestal attached tissues. Sohn's poncho technique is a technique that utilizes a healing abutment at the implant site to stabilize the Platelet Rich Fibrin membrane. Thus, the aim of this study is to evaluate the efficacy of Sohn's poncho technique used for placement of leukocyte platelet rich fibrin (L-PRF) membrane in improving the peri-implant mucosal thickness and width of keratinized mucosa as well as in the acceleration of healing process compared to the peri-implant mucosa surrounding healing abutments placed without the L-PRF membrane. MATERIALS AND METHODS A split mouth randomized controlled clinical trial was designed in which implants were placed in the mandibular posterior region. Healing abutment is placed along with the L-PRF membrane at the test site using Sohn's poncho technique and at control site conventional healing abutment placement was done at second stage. The thickness of peri-implant mucosa as primary outcome and the Width of keratinized tissue and healing as secondary outcomes were measured and assessed at various time intervals. RESULTS Statistically significant difference was seen in inter-group analysis when peri-implant mucosal thickness (3.8mm ± 0.4 vs 2.3mm ± 0.4) and width of keratinized mucosa (3.6mm ± 0.6 vs 2.7mm ± 0.3) in test and control groups respectively and intra-group analysis of test and control groups at 4 weeks and 6 weeks' time points. The control group showed faster healing when compared to the test group. CONCLUSION Sohn's poncho technique in combination with L-PRF has the potential to improve the thickness of peri-implant mucosa and the width of keratinized mucosa around implants. This article is protected by copyright. All rights reserved.

This study aimed to evaluate the correlation between epidermal growth factor (EGF) and receptor (EGFR) levels in different clinical stages of dental implant rehabilitation and trace mucositis development’s biological profile. Thirty-six participants from the Specialization in Implant Dentistry, Universidade Federal Fluminense, Brazil, were included in the study and underwent sample collection: inside the alveolar socket, immediately before implant placement (Group 1, n = 10); at the peri-implant crevicular fluid (PICF) during reopening (Group 2, n = 10); PICF from healthy peri-implant in function (Group 3, n = 8); and PICF from mucositis sites (Group 4, n = 18). Quantitative polymerase chain reaction (PCR) evaluated EGF/EGFR gene expression using the SYBR Green Master Mix detection system. The results showed that EGF expression in the peri-implant crevicular fluid was statistically different. There was a higher EGF expression for group C (peri-implant health) (p = 0.04) than for the other groups. Regarding EGFR, there was no statistical difference among the groups (p = 0.56). It was concluded that low levels of EGF gene expression in the peri-implant crevicular fluid are related to the development of peri-implant mucositis and the absence of mucosae sealing. There was no correlation between EGFR gene expression with health or mucositis.

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

Abstract This experimental study aimed to evaluate the effects of injectable platelet-rich fibrin (i-PRF) on mucosal healing and the release of growth factors in rats. 40 rats were used; i-PRF was administered in the right buccal area while saline was injected in the left. Cytokeratin, FGF, PDGF, TGF, and VEGF expressions were determined with immunohistochemistry. Gene expressions of EGF, TGF-β, and VEGF were analysed. Epithelialization started on the 3rd day, and connective tissue maturation was more prominent in the i-PRF-applied group. Also, the releases of VEGF, EGF, TGF-β, PDGF, and FGF were higher in the i-PRF group during the 14 days. Gene expression analysis showed that changes in TGF-β at 14 days after i-PRF injection and VEGF after 21 days were statistically significant. The results of this study suggested that autologous i-PRF application enhanced the healing of oral mucosal wounds by increasing the release of growth factors for 21 days.

Oral mucosal wounds are characterized by rapid healing with minimal scarring, partly attributable to the “enhanced” wound healing properties of oral mucosal fibroblasts (OMFs). Hepatocyte growth factor (HGF) is a pleiotropic growth factor, with potential key roles in accelerating healing and preventing fibrosis. HGF can exist as full-length or truncated (HGF-NK), NK1 and NK2 isoforms. As OMFs display elevated HGF expression compared to dermal fibroblasts (DFs), this study investigated the extent to which HGF mediates the preferential cellular functions of OMFs, and the influence of pro-fibrotic, transforming growth factor-β1 (TGF-β1) on these responses. Knockdown of HGF expression in OMFs by short-interfering RNA (siHGF) significantly inhibited OMF proliferative and migratory responses. Supplementation with exogenous TGF-β1 also significantly inhibited proliferation and migration, concomitant with significantly down-regulated HGF expression. In addition, knockdown abrogated OMF resistance to TGF-β1-driven myofibroblast differentiation, as evidenced by increased α-smooth muscle actin (α-SMA) expression, F-actin reorganisation, and stress fibre formation. Responses were unaffected in siHGF-transfected DFs. OMFs expressed significantly higher full-length HGF and NK1 levels compared to patient-matched DFs, whilst NK2 expression was similar in both OMFs and DFs. Furthermore, NK2 was preferentially expressed over NK1 in DFs. TGF-β1 supplementation significantly down-regulated full-length HGF and NK1 expression by OMFs, while NK2 was less affected. This study demonstrates the importance of HGF in mediating “enhanced” OMF cellular function. We also propose that full-length HGF and HGF-NK1 convey desirable wound healing properties, whilst fibroblasts preferentially expressing more HGF-NK2 readily undergo TGF-β1-driven differentiation into myofibroblasts.

Introduction: The aim of the present study was to compare the effects of laser and basic fibroblastic growth factor (bFGF) treatment on operative wound healing in a rat model. Methods: Sixty-six male Wistar rats were employed in this study. A 10-mm surgical wound was created on the buccal mucosa of each rat, under anesthesia, and then the rats were divided into 3 groups of 22: (1) GF group (received subcutaneous injection of bFGF), (2) laser group (treated with low-level laser irradiation), and (3) control group (received no treatment). On day 5, half of the rats in each group and on day 10 the other half, were sacrificed. Afterward, samples were taken from rats' buccal mucosa for histological assay and scoring. The data were analyzed using MannWhitney test (α =5%). Results: On day 5 there was not any significant difference between GF and control groups; however, the laser group showed clinically delayed wound coverage, compared to other groups (P<0.05). On day 10, histological examination demonstrated marked vascular granulation tissue ( GT) in GF group. Collagen production was significantly prominent in laser group compared to GF treated samples (P=0.004). Inflammation of GT in GF and laser groups was significantly less than that in control samples (P=0.005 and P=0.001, respectively). Conclusion: The components of wound matrix induced by GF and laser treatment were significantly different. Although bFGF or laser treatment of oral wounds, under the conditions of the present study, did not accelerate wound healing, they showed some other notable effects on the quality of healing.

Introduction: Modern dentistry aims to restore the comfort and health of the stomatognathic system. Dental implants have emerged as a promising option for this purpose. Concentrated growth factors (CGFs) have been suggested to enhance the healing of bone grafts and enhance the integration of implants into the bone. Growth factors are proteins which regulate the complex process of wound healing. They play an important role in cell migration, cell proliferation, and angiogenesis in the tissue regeneration phase. CGF was first developed by Sacco in 2006. It can be used as a barrier membrane to accelerate soft-tissue healing. CGF does not require any chemical or anticoagulants, and hence, it is free from viral transmission diseases. Crestal bone levels, peri-implant bone density, bleeding, probing depth, mobility, occlusion factors, restoration adequacy, radiographic images, oral hygiene, and patient health status are some of the important parameters for determining longevity of success rates in implant dentistry. This study will assess the peri-implant bone density and crestal bone levels with and without the use of CGF. Aim: To evaluate the effect of CGFs on peri-implant bone density and in the preservation of crestal bone levels around dental implants. Materials and Methods: Sampling procedure: Random selection of population (Sealed envelope method) Number of groups: Two-Control group (Group 1) and Experimental group (Group 2) Sample size: 20 For Group 2, implants were placed with CGF. For Group 1, implants were placed without CGF. The peri-implant bone density and bone levels were measured by Digora and signora software. Results: The mean crestal bone loss on the mesial aspect of implants placed in Group 2 is 0.294 mm and Group 1 is 0.345 mm, and the mean crestal bone loss on the distal aspect of implants placed in Group 2 is 0.320 mm and in Group 1 is 0.331 mm. There are no many significant differences on mesial and distal aspects around implants between the two groups Intragroup comparison of bone density values in Group 1 shows the mean difference from baseline to 1 month is 0.6, and after three and 6 months periods are 1.1 and 1.1, respectively, which indicates not much significant improvement in bone density values in Group 1. Intergroup comparison shows a significant difference between both the groups starting from as early as the 1st month. Conclusion: The results of this study indicate that CGF is significantly better in the regeneration of bone around the implants when comparing with nonCGF groups. Although CGF showed improvement in bone formation, there are no many differences in crestal bone level changes on mesial and distal sides of the implants between the two groups.

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