A Glutathione Peroxidase-Mimicking Nanozyme Precisely Alleviates Reactive Oxygen Species and Promotes Periodontal Bone Regeneration.

The use of oxidoreductase nanozymes to regulate reactive oxygen species (ROS) has gradually emerged in periodontology treatments. However, current nanozymes for treating periodontitis eliminate ROS extensively and non-specifically, ignoring the physiological functions of ROS under normal conditions, which may result in uncontrolled side effects. Herein, using the MIL-47(V)-F (MVF) nanozyme, which mimics the function of glutathione peroxidase (GPx), it is proposed that ROS can be properly regulated by specifically eliminating H2 O2 , the most prominent ROS. Through H2 O2 elimination, MVF contributes to limiting inflammation, regulating immune microenvironment, and promoting periodontal regeneration. Moreover, MVF stimulates osteogenic differentiation of periodontal stem cells directly, further promoting regeneration due to the vanadium in MVF. Mechanistically, MVF regulates ROS by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) pathway and promotes osteogenic differentiation directly through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. A promising periodontitis therapy strategy is presented using GPx-mimicking nanozymes through their triple effects of antioxidation, immunomodulation, and bone remodeling regulation, making nanozymes an excellent tool for developing precision medicine.

Injectable CNPs/DMP1-loaded self-assembly hydrogel regulating inflammation of dental pulp stem cells for dentin regeneration.

Vital pulp preservation, which is a clinical challenge of aseptic or iatrogenic accidental exposure of the pulp, in cases direct pulp capping is the main technology. Human dental pulp stem cells (hDPSCs) play a critical role in pulp tissue repair, but their differentiative ability could be inhibited by the potential infection and inflammatory response of the exposed pulp. Therefore, inflammatory regulation and differentiated promotion of hDPSCs are both essential for preserving living pulp teeth. In this study, we constructed a functional dental pulp-capping hydrogel by loading cerium oxide nanoparticles (CNPs) and dentin matrix protein-1 (DMP1) into an injectable Fmoc-triphenylalanine hydrogel (Fmoc-phe3 hydrogel) as CNPs/DMP1/Hydrogel for in situ drugs delivery. With a view to long-term storage and release of CNPs (anti-inflammatory and antioxidant) to regulate the local inflammatory environment and DMP1 to promote the regeneration of dentin. Results of CCK-8, LDH release, hemolysis, and Live/Dead assessment of cells demonstrated the good biocompatibility of CNPs/DMP1/Hydrogel. The levels of alkaline phosphatase activity, quantification of the mineralized nodules, expressions of osteogenic genes and proteins demonstrated CNPs/DMP1/Hydrogel could protect the activity of hDPSCs' osteogenic/dentinogenic differentiation by reducing the inflammation response via releasing CNPs. The therapy effects were further confirmed in rat models, CNPs/DMP1/Hydrogel reduced the necrosis rate of damaged pulp and promoted injured pulp repair and reparative dentin formation with preserved vital pulps. In summary, the CNPs/DMP1/Hydrogel composite is an up-and-coming pulp-capping material candidate to induce reparative dentin formation, as well as provide a theoretical and experimental basis for developing pulp-capping materials.

Remodeling periodontal osteoimmune microenvironment through MAPK/NFκB phosphorylation pathway of macrophage via intelligent ROS scavenging.

Periodontitis is an inflammatory disorder which leads to the defect of tooth-supporting tissue, especially in alveolar bone. During this process, the polarization behavior of macrophages affects immune inflammation and bone regeneration in which reactive oxygen species (ROS) play an essential role. ROS level should be regulated to the physiological level to protect stem cells from the inflammatory immune microenvironment. Our previous study constructed a ROS-responsive nanoplatform (Pssl-NAC), which possessed ROS-responsive antioxidative effect and could be potentially applied in periodontitis. However, the connection among bone regeneration, inflammation and oxidative stress remained in osteoimmune regulation is not clear. To further investigate the mechanism of the way how Pssl-NAC works in the treatment of periodontitis would be meaningful. Here, we investigated the effect of PssL-NAC in the regulation of the osteoimmune microenvironment through macrophage polarization. Results show PssL-NAC regulated the macrophage polarization direction in an inflammatory environment by maintaining an appropriate level of intracellular ROS, in which the MAPK/NFκB phosphorylation pathway is particularly important. In the macrophage-human periodontal ligament stem cells (hPDLSCs) co-culture system, PssL-NAC treatment significantly enhanced the osteogenic differentiation of hPDLSCs. In vivo experiment further confirmed the M2-like macrophages increased in the periodontal tissue of rats, and the expression of iNOS and p65 decreased after PssL-NAC treatment. In conclusion, PssL-NAC regulates the osteoimmune microenvironment and protects stem cells from oxidative stress injury for bone regeneration, which provides a strategy for the treatment of periodontitis.

Combined Black Phosphorus Nanosheets with ICG/aPDT is an Effective Anti-Inflammatory Treatment for Periodontal Disorders.

Introduction: Antibacterial photodynamic treatment (aPDT) has indispensable significance as a means of treating periodontal disorders because of its extraordinary potential for killing pathogenic bacteria by generating an overpowering amount of reactive oxygen species (ROS). The elevated ROS that may result from the antibacterial treatment procedure, however, could exert oxidative pressure inside periodontal pockets, causing irreparable damage to surrounding tissue, an issue that has severely restricted its medicinal applications. Accordingly, herein, we report the use of black phosphorus nanosheets (BPNSs) that can eliminate the side effects of ROS-based aPDT as well as scavenge ROS to produce an antibacterial effect. Methods: The antibacterial effect of ICG/aPDT was observed by direct microscopic colony counting. A microplate reader and confocal microscope enabled measurements of cell viability and the quantification of ROS fluorescence. BPNS administration regulated the oxidative environment. IL-1ß, IL-6, TNF-α, IL-10, TGF-ß, and Arg-1 mRNA expression levels were used to assess the inflammatory response after BPNS treatment. In vivo, the efficacy of the combination of BPNSs and ICG/aPDT was evaluated in rats with periodontal disease by histomorphometric and immunohistochemical analyses. Results: The CFU assay results verified the antibacterial effect of ICG/aPDT treatment, and ROS fluorescence quantification by CLSM indicated the antioxidative ability of the BPNSs. IL-1ß, IL-6, TNF-α, IL-10, TGF-ß, and Arg-1 mRNA expression levels were significantly decreased after BPNS treatment, confirming the in vitro anti-inflammatory effect of this nanomaterial. The histomorphometric and immunohistochemical analyses showed that the levels of proinflammatory factors decreased, suggesting that the BPNSs had anti-inflammatory effects in vivo. Conclusion: Treatment with antioxidative BPNSs gives new insights into future anti-inflammatory therapies for periodontal disease and other infection-related inflammatory illnesses and provides an approach to combat the flaws of aPDT.

Polyvinyl chloride degradation by a bacterium isolated from the gut of insect larvae.

Evidence for microbial degradation of polyvinyl chloride (PVC) has previously been reported, but little is known about the degrading strains and enzymes. Here, we isolate a PVC-degrading bacterium from the gut of insect larvae and shed light on the PVC degradation pathway using a multi-omic approach. We show that the larvae of an insect pest, Spodoptera frugiperda, can survive by feeding on PVC film, and this is associated with enrichment of Enterococcus, Klebsiella and other bacteria in the larva's gut microbiota. A bacterial strain isolated from the larval intestine (Klebsiella sp. EMBL-1) is able to depolymerize and utilize PVC as sole energy source. We use genomic, transcriptomic, proteomic, and metabolomic analyses to identify genes and proteins potentially involved in PVC degradation (e.g., catalase-peroxidase, dehalogenases, enolase, aldehyde dehydrogenase and oxygenase), and propose a PVC biodegradation pathway. Furthermore, enzymatic assays using the purified catalase-peroxidase support a role in PVC depolymerization.

Micro(nano)plastic size and concentration co-differentiate nitrogen transformation, microbiota dynamics, and assembly patterns in constructed wetlands.

Micro/nano-sized plastics (MPs/NPs) existing in wastewater system are the potential threats to nitrogen (N) biotransformation. Constructed wetlands (CWs) as wastewater treatment systems are considered the important barriers preventing MPs/NPs from entering the open water. However, little is known about how the accumulation of MPs/NPs affects microbial N transformation, dynamics, assembly, and metabolism of wetland microbiota. Herein, we constructed 12 wetland systems to address the above knowledge gaps over 300-day exposure to different sizes (3 mm - 60 nm) and concentrations (10 - 1000 µg/L) of MPs/NPs. The results showed that MPs/NPs accumulation caused decrease in NH4+-N removal (by 7.6% - 71.2%) and microbial diversity and intriguingly altered microbiota composition (especially in the high-concentration groups) without damage on the high removal efficiency of NO3--N and NO2--N (66.2% - 99.8%) in all except for the nano-sized plastic-exposed wetlands. Moreover, MPs/NPs exposure induced shift in the strengths of non-random species aggregation and segregation patterns co-differentiated by the size and concentration of MPs/NPs, and MPs/NPs accumulation created size-differentiated alternative niches for nitrogen-transforming bacteria, e.g., canonical nitrifiers (Nitrospira and Nitrosomonas) and denitrifiers (Thauera, Comamonas, and Aquabacterium), which were enriched in MPs groups where denitrifying enzyme-coding genes were also enriched, suggesting potential positive impact of larger plastics on denitrification. Our study highlights MPs/NPs-induced divergence in microbiota dynamics and nitrogen transformation in CWs, and provides important insights into how microbiota structurally and functionally respond to long-term MPs/NPs disturbance.