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Background: Improving the microenvironment to augment endogenous regenerative potential has emerged as a fundamental concept for stimulating and expediting periodontal tissue repair and regeneration. Previous studies have demonstrated that TPPU, a soluble epoxide hydrolase inhibitor (sEHi), mediates the suppression of inflammatory bone loss in periodontitis models. However, the underlying mechanisms remain largely elusive. Methods: In this study, we constructed a human umbilical vein endothelial cell (HUVEC) and periodontal ligament stem cell (PDLSC) coculture system in vitro and tested the anti-inflammatory effect of TPPU under inflammatory conditions. The roles of HIF-1α and Endomucin (EMCN) in the anti-inflammatory effects of TPPU were analyzed. The effects of TPPU on osteogenesis and osteoclastogenesis in cocultured cells were examined. The in vivo periodontitis model further verified the effects of TPPU on inhibiting neutrophil adhesion and inflammation and inhibiting osteoclasts. Results: Our in vitro experiments demonstrated that TPPU enhances the interaction between mesenchymal stem cells and vascular endothelial cells to enhance anti-inflammatory and osteogenic differentiation effects and revealed a new anti-inflammatory mechanism of TPPU involving the upregulation of EMCN in endothelial cells to prevent lymphocyte recruitment. We also confirmed that TPPU inhibits osteoclast activity. Our in vivo findings showed that TPPU inhibits osteoclast activity and neutrophil adhesion and enhances periodontal tissue repair and regeneration. Conclusions: TPPU promotes local regeneration in periodontitis by inhibiting inflammation and bone resorption. Thus, targeting soluble epoxide hydrolase represents an endogenous regenerative strategy for periodontitis treatment. [ABSTRACT FROM AUTHOR]

Background: Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. Methods: Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. Results: LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. Conclusions: LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Cobalt–chromium (Co-Cr) alloys have been widely used as dental-restoration materials for many years. This study sought to investigate whether selective laser melting (SLM) is a more appropriate process than traditional casting (CAST) for fabricating dental Co-Cr alloys. Metallurgical microscopy, X-ray photoelectron spectroscopy (XPS), Vickers hardness and nanoindentation tests, and friction and wear tests were used to evaluate the microstructure, surface compositions, mechanical properties, and wear resistance, respectively. Additionally, the biocompatibilities and cell adhesion of the alloys were evaluated with L-929 fibroblasts via CCK-8 assay, Live/Dead staining, flow cytometric analysis, scanning electron microscopy (SEM) observation and real-time PCR (RT-PCR) assay. The XPS results showed that the two alloys were all mainly comprised of Co, Cr, and O. The hardness in the CAST group equaled 7.15 ± 0.48 GPa, while in the SLM group, it equaled 9.06 ± 0.49 GPa. The friction coefficient of SLM alloys remained at approximately 0.46, but the CAST specimens fluctuated significantly. SLM alloys exhibited shallower wear scars and less wear debris compared with CAST alloys, simultaneously. Additionally, there were higher survival and expression of cell-adhesion-related genes on SLM alloys of L-929 cells, which meant that the deleterious effect on L-929 cells was significantly reduced compared with that for the CAST alloys. Overall, the wear resistances and biocompatibilities of the Co-Cr dental alloys were dramatically affected by the fabrication technique. The SLM technique is advantageous over the CAST technique for fabricating Co-Cr dental alloys. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) membranes are widely used to treat bone defects. In this study, sequential electrospinning and electrospraying techniques were used to prepare a dual-layer GBR membrane composed of gelatin (Gel) and chitosan (CS) containing simvastatin (Sim)-loaded poly(lactic- co -glycolic acid) (PLGA) microspheres (Sim@PLGA/Gel-CS). As a GBR membrane, Sim@PLGA/Gel-CS could act as a barrier to prevent soft tissue from occupying regions of bone tissue. Furthermore, compared with traditional GBR membranes, Sim@PLGA/Gel-CS played an active role on stimulating osteogenesis and angiogenesis. Determination of the physical, chemical, and biological properties of Sim@PLGA/Gel-CS membranes revealed uniform sizes of the nanofibers and microspheres and appropriate morphologies. Fourier-transform infrared spectroscopy was used to characterize the interactions between Sim@PLGA/Gel-CS molecules and the increase in the number of amide groups in crosslinked membranes. The thermal stability and tensile strength of the membranes increased after N-(3-dimethylaminopropyl)-N9- ethylcarbodiimide/N-hydroxysuccinimide crosslinking. The increased fiber density of the barrier layer decreased fibroblast migration compared with that in the osteogenic layer. Osteogenic function was indicated by the increased alkaline phosphatase activity, calcium deposition, and neovascularization. In conclusion, the multifunctional effects of Sim@PLGA/Gel-CS on the barrier and bone microenvironment were achieved via its dual-layer structure and simvastatin coating. Sim@PLGA/Gel-CS has potential applications in bone tissue regeneration. Typical membranes were divided into osteogenic and barrier layers. The osteoblast layer promoted the adhesion and proliferation of MC3T3-E1 cells and HUVECs, whereas the barrier layer effectively inhibited the aggressive growth of L929 cells. [Display omitted] • Compared with traditional guided bone regeneration (GBR) membranes, the simvastatin in poly(lactic- co -glycolic acid) microspheres with gelatin and chitosan (Sim@PLGA/Gel-CS) proven with multiple functions in preventing occupy growth, and stimulating osteogenesis and angiogenesis that was hoped to obtain multi-functional GBR membranes. • PLGA microspheres among Gel-CS fibers used as a drug-release system enabled prolonged release of simvastatin, which maintained the local dose and avoided the side effects of systemic administration. • In addition to the Sim coating, Sim@PLGA/Gel-CS was prepared as two layers with different structures: an osteogenic layer with loose fibers containing Sim@PLGA microspheres and a barrier layer with compact fibers. This design is beneficial for preventing soft tissue damage and promoting bone tissue repair. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) membranes are widely used to treat bone defects. In this study, sequential electrospinning and electrospraying techniques were used to prepare a dual-layer GBR membrane composed of gelatin (Gel) and chitosan (CS) containing simvastatin (Sim)-loaded poly(lactic- co -glycolic acid) (PLGA) microspheres (Sim@PLGA/Gel-CS). As a GBR membrane, Sim@PLGA/Gel-CS could act as a barrier to prevent soft tissue from occupying regions of bone tissue. Furthermore, compared with traditional GBR membranes, Sim@PLGA/Gel-CS played an active role on stimulating osteogenesis and angiogenesis. Determination of the physical, chemical, and biological properties of Sim@PLGA/Gel-CS membranes revealed uniform sizes of the nanofibers and microspheres and appropriate morphologies. Fourier-transform infrared spectroscopy was used to characterize the interactions between Sim@PLGA/Gel-CS molecules and the increase in the number of amide groups in crosslinked membranes. The thermal stability and tensile strength of the membranes increased after N-(3-dimethylaminopropyl)-N9- ethylcarbodiimide/N-hydroxysuccinimide crosslinking. The increased fiber density of the barrier layer decreased fibroblast migration compared with that in the osteogenic layer. Osteogenic function was indicated by the increased alkaline phosphatase activity, calcium deposition, and neovascularization. In conclusion, the multifunctional effects of Sim@PLGA/Gel-CS on the barrier and bone microenvironment were achieved via its dual-layer structure and simvastatin coating. Sim@PLGA/Gel-CS has potential applications in bone tissue regeneration. Typical membranes were divided into osteogenic and barrier layers. The osteoblast layer promoted the adhesion and proliferation of MC3T3-E1 cells and HUVECs, whereas the barrier layer effectively inhibited the aggressive growth of L929 cells. [Display omitted] • Compared with traditional guided bone regeneration (GBR) membranes, the simvastatin in poly(lactic- co -glycolic acid) microspheres with gelatin and chitosan (Sim@PLGA/Gel-CS) proven with multiple functions in preventing occupy growth, and stimulating osteogenesis and angiogenesis that was hoped to obtain multi-functional GBR membranes. • PLGA microspheres among Gel-CS fibers used as a drug-release system enabled prolonged release of simvastatin, which maintained the local dose and avoided the side effects of systemic administration. • In addition to the Sim coating, Sim@PLGA/Gel-CS was prepared as two layers with different structures: an osteogenic layer with loose fibers containing Sim@PLGA microspheres and a barrier layer with compact fibers. This design is beneficial for preventing soft tissue damage and promoting bone tissue repair. [ABSTRACT FROM AUTHOR]