Biomaterials science and surface engineering strategies for dental peri-implantitis management.

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.

Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

Mechanical properties, in vitro biodegradable behavior, biocompatibility and osteogenic ability of additively manufactured Zn-0.8Li-0.1Mg alloy scaffolds.

Alloying and structural design provide flexibility to modulate performance of biodegradable porous implants manufactured by laser powder bed fusion (L-PBF). Herein, bulk Zn-0.8Li-0.1Mg was first fabricated to indicate the influence of the ternary alloy system on strengthening effect. Porous scaffolds with different porosities, including 60 % (P60), 70 % (P70) and 80 % (P80), were designed and fabricated to study the influence of porosity on mechanical properties, in vitro degradation behavior, biocompatibility and osteogenic ability. Pure Zn (Zn-P70) scaffolds with a porosity of 70 % were utilized for the comparison. The results showed Zn-0.8Li-0.1Mg bulks had an ultimate tensile strength of 460.78 ± 5.79 MPa, which was more than 3 times that of pure Zn ones and was the highest value ever reported for Zn alloys fabricated by L-PBF. The compressive strength (CS) and elastic modulus (E) of scaffolds decreased with increasing porosities. The CS of P70 scaffolds was 24.59 MPa, more than 2 times that of Zn-P70. The weight loss of scaffolds during in vitro immersion increased with increasing porosities. Compared with Zn-P70, a lower weight loss, better biocompatibility and improved osteogenic ability were observed for P70 scaffolds. P70 scaffolds also exhibited the best biocompatibility and osteogenic ability among all the used porosities. Influence mechanism of alloying elements and structural porosities on mechanical behaviors, in vitro biodegradation behavior, biocompatibility and osteogenic ability of scaffolds were discussed using finite element analysis and the characterization of degradation products. The results indicated that the proper design of alloying and porosity made Zn-0.8Li-0.1Mg scaffolds promising for biodegradable applications.

Eldecalcitol inhibits the progression of oral cancer by suppressing the expression of GPx-1.

OBJECTIVES: This study aimed to investigate the role of eldecalcitol in the progression of oral squamous cell carcinoma and to explore the related mechanism. MATERIALS AND METHODS: The effects of eldecalcitol on the proliferation, cell cycle, apoptosis, and migration of oral cancer cells (SCC-15 and CAL-27) were evaluated with cell counting kit-8, flow cytometry, quantitative real-time polymerase chain reaction, western blotting, and scratch assay. Mouse xenograft tumor model was established to further confirm the role of eldecalcitol in the progression of oral cancer. Immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting were used to detect glutathione peroxidase-1 expression in oral cancer tissue and cells treated with eldecalcitol. RESULTS: Eldecalcitol was found to inhibit the proliferation and migration of SCC-15 and CAL-27 cells significantly, block the cell cycle in the G0/G1 phase, and enhance the apoptosis. In addition, glutathione peroxidase-1 was downregulated by eldecalcitol and acted as an important medium of eldecalcitol in inhibiting the proliferation and migration of SCC-15 and CAL-27 cells, as well as promoting their apoptosis. CONCLUSIONS: Eldecalcitol may inhibit the progression of oral cancer by suppressing the expression of glutathione peroxidase-1, which may provide new insight into the application of eldecalcitol as a potential anti-cancer drug.

Regulatory T cells showed characteristics of T helper-17(Th17) cells in mice periodontitis model.

OBJECTIVES: This study aimed to clarify the regulatory role of Th17-Treg balance in periodontitis and further reveal Treg plasticity. MATERIALS AND METHODS: An experimental periodontitis model was established by ligation and injection of Pg-LPS. Inflammatory factors were measured by ELISA and RT-PCR. Alveolar bone absorption was evaluated by micro-CT and histomorphology. Quantities of Treg and Th17 cell and their related gene expression were examined. Furthermore, after magnetic bead-sorting spleen Treg cells, Treg/Th17 characteristic genes were explored. Immunofluorescence double staining of Foxp3 and IL-17 was conducted to further reveal Treg plasticity. RESULTS: Inflammatory cytokines in serum and gingival tissue increased significantly in periodontitis, which revealed obvious crestal bone loss. Further analysis showed that the number of Th17 cells and expression of related genes increased more significantly than Treg cells, demonstrating Treg-Th17 imbalance. Flow cytometry showed that the proportions of Treg cells in the blood and spleen were lower in periodontitis group. Furthermore, Foxp3 was downregulated, and Rorc/ IL-17A were increased in Treg cells of periodontitis group. Immunofluorescence double staining showed significantly increased number of IL-17+Foxp3+ cells in periodontitis. CONCLUSIONS: These results provided evidence that Treg cells showed characteristics of Th17 cells in mice with periodontitis, although its mechanisms require further study.

Periostin regulates LPS-induced apoptosis via Nrf2/HO-1 pathway in periodontal ligament fibroblasts.

OBJECTIVE: Periostin is important for the maintenance of periodontal tissue, but its role in periodontitis is controversial. This research investigated the effect of periostin in periodontitis and the underlying mechanism. DESIGN: Mouse periodontitis models in vivo and inflammation model in vitro which were induced by Porphyromonas gingivalis lipopolysaccharide were established to evaluate periostin expression. Human periodontal ligament fibroblasts (PDLFs) were treated with lipopolysaccharide and N-acetylcysteine, fluorescence staining, flow cytometry, Western blot, and qRT-PCR were used to detect reactive oxygen species (ROS), periostin expression, and apoptosis-related makers. The periostin gene was successfully transfected into PDLFs to verify the effect of periostin on apoptosis. Then, the Nrf2 inhibitor was added to clarify the mechanism. RESULTS: Periostin expression decreased in the periodontal ligaments of mouse periodontitis models and lipopolysaccharide-induced PDLFs. Lipopolysaccharide promoted the activation of ROS and apoptosis in PDLFs, whereas N-acetylcysteine reversed this condition. Overexpression of periostin suppressed apoptosis of PDLFs and reversed the inhibitory effect of lipopolysaccharide on nuclear Nrf2 expression. Moreover, the Nrf2 inhibitor attenuated the protective effect of periostin on lipopolysaccharide-induced apoptosis. CONCLUSIONS: Lipopolysaccharide induced apoptosis in PDLFs by inhibiting periostin expression and thus Nrf2/HO-1 pathway, indicating that periostin could be a potential therapeutic target for periodontitis.

Exendin-4 and eldecalcitol synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells through M2 macrophages polarization via PI3K/AKT pathway.

BACKGROUND: The incidence of diabetic osteoporosis is increasing. This article evaluates the effect of combination treatment with the hypoglycemic drug exendin-4 (Ex-4) and the vitamin D analog eldecalcitol (ED-71) on improving diabetic osteoporosis and explores the relevant mechanism of action. METHOD: Micro-CT, HE staining, immunohistochemistry, qPCR and ELISA were used to evaluate the impact of Ex-4 and ED-71 on bone formation and macrophage polarization in a mouse model of diabetic osteoporosis in vivo. Immunofluorescence, flow cytometry and qPCR were used to characterize the polarization type of macrophages treated with Ex-4 and ED-71 in vitro. A co-culture system of BMSCs and macrophages was established. Subsequently, crystal violet staining, alkaline phosphatase staining and alizarin red staining were used to evaluate the migration and osteogenesis differentiation of BMSCs. RESULTS: Ex-4 combined with ED-71 significantly reduced blood glucose levels and enhanced bone formation in mice with diabetic osteoporosis. In addition, Ex-4 synergized with ED-71 to induce the polarization of macrophages into M2 through the PI3K/AKT pathway. Macrophages treated with the combination of Ex-4 and ED-71 can significantly induce the osteogenic differentiation of BMSCs. CONCLUSION: Ex-4 synergized with ED-71 to reduce blood glucose levels significantly. And this combination therapy can synergistically induce osteogenic differentiation of BMSCs by promoting M2 macrophages polarization, thereby improving diabetic osteoporosis. Therefore, the combination of Ex-4 and ED-71 may be a new strategy for the treatment of diabetic osteoporosis.

As a Novel Tumor Suppressor, LHPP Promotes Apoptosis by Inhibiting the PI3K/AKT Signaling Pathway in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) refers to the malignant tumor of the head and neck with a highest morbidity. It exhibits a poor prognosis and unsatisfactory treatment partially attributed to delayed diagnosis. As indicated from existing reports, the protein histidine phosphatase LHPP acts as a vital factor in tumorigenesis in liver, lung, bladder, breast and pancreatic tumor tissues. Thus far, the functional mechanism of LHPP in OSCC remains unclear. DGE analysis, OSCC cell lines and OSCC cases were found that LHPP was down-regulated in OSCC tissues and cells compared with that in normal oral mucosa tissues and cells, and was closely related to OSCC differentiation. Cell counting Kit 8 test, EdU proliferation test, scratches test, invasion test, monoclonal formation test, mouse xenograft tumor model, HE staining and immunohistochemistry showed that LHPP inhibited OSCC growth, proliferation and migration in vivo and in vitro. GO and KEGG enrichment analysis, LHPP transcription factor analysis and flow cytometry found that LHPP promotes the apoptosis of OSCC by decreasing the transcriptional activity of p-PI3K and p-Akt. Finally, our results suggested that LHPP inhibited the progression of OSCC through the PI3K/AKT signaling pathway, indicating that LHPP may be a new target for the treatment of OSCC.

Measurement and Inspection of Photo-Realistic 3-D VR Models.

Recent advancements in virtual reality (VR) may help unlock the full potential offered by 3-D photorealistic models generated using state-of-the-art photogrammetric methods. Using VR to carry out analyses on photogrammetric models has the potential to assist the user in performing basic offline engineering inspection of digital twins-digitized representations of real-world objects and structures. However, for such benefits to materialize, it is necessary to create suitable interactive systems for working with photogrammetric models in VR. To this end, this article presents PhotoTwinVR-an immersive gesture-controlled system for manipulation and inspection of 3-D photogrammetric models of physical objects in VR. An observational study with three domain experts validates the feasibility of the system design for practical use-cases involving offline inspections of pipelines and other 3-D structures.

Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt/Beta catenin signaling pathway.

OBJECTIVES: The aims of this study were to explore: (ⅰ) the effect of Notum on periodontitis in vivo; (ⅱ) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro; and (ⅲ) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs. DESIGN: C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum. In in vitro experiments, Western blot, qRT- PCR and ELISA were used to examine the expression of Notum in a lipopolysaccharide-induced inflammation model. Alkaline phosphatase staining was used to evaluate alkaline phosphatase activity. Western blot and qRT - PCR were used to measure the expression of osteogenic-related markers after adding human recombinant Notum and Notum inhibitor ABC99. In addition, LiCl, an agonist of the Wnt/Beta-catenin signaling pathway, was added to explore using Western blot whether Notum was involved in regulating the osteogenic differentiation of human periodontal ligament stem cells through the Wnt/Beta-catenin signaling pathway. RESULTS: Notum was highly expressed in periodontal tissues of mice and lipopolysaccharide-induced inflammation cell model. The protein and messenger ribonucleic acid levels of hPDLSCs osteogenic markers were reduced after adding human recombinant Notum. However, the inhibitory effect of Notum on the osteogenic differentiation of hPDLSCs could be significantly reversed by adding LiCl. CONCLUSION: These results demonstrated that Notum inhibited the osteogenic differentiation of hPDLSCs probably via the Wnt/Beta-catenin the downstream signaling pathway.

Oxidative stress induced pyroptosis leads to osteogenic dysfunction of MG63 cells.

Periodontitis is characterized by alveolar bone destruction and is one of the most common chronic oral diseases. Inflammatory cytokines released by pyroptosis, which can be triggered by oxidative stress, are critical in the development of periodontitis. This study aims to clarify whether oxidative stress causes osteoblast dysfunction by inducing pyroptosis in the process of periodontitis. We found that treatment with lipopolysaccharide (LPS) led to NLRP3 inflammasome-mediated pyroptosis of MG63 cells as well as decreased cell migration. Of note, LPS stimulation increased LDH release in a time- and dose-dependent manner. However, inhibition of reactive oxygen species with N-acetyl-L-cysteine attenuated oxidative stress-mediated pyroptosis and improved migration injury in osteoblasts treated with LPS. Further, inhibition of the NLRP3 inflammasome with MCC950 improved osteoblast migration and restored the expression of osteogenic differentiation-related proteins such as COL 1, RUNX 2 and ALP. In conclusion, oxidative stress caused by LPS induces pyroptosis in osteoblasts, leading to osteogenic dysfunction.