TCPP/MgO-loaded PLGA microspheres combining photodynamic antibacterial therapy with PBM-assisted fibroblast activation to treat periodontitis.

Bacteria eradication and subsequent periodontal tissue reconstruction is the primary task for periodontitis treatment. Commonly used antibiotic therapy suffers from antibiotic resistance. Meanwhile, promoting fibroblast activity is crucial for re-establishing a damaged periodontal structure. In addition to the fibroblast activation property of Mg2+, photobiomodulation (PBM) has recently attracted increasing attention in wound healing. Using the same 635 nm laser resource, PBM could simultaneously work with antibacterial photodynamic therapy (aPDT) to achieve antibacterial function and fibroblast activation effect. Herein, multifunctional microspheres were designed by employing poly (lactic-co-glycolic acid) (PLGA) microspheres to load tetrakis (4-carboxyphenyl) porphyrin (TCPP) and magnesium oxide (MgO) nanoparticles, named as PMT, with sustained Mg2+ release for 20 days. PMT achieved excellent antibacterial photodynamic effect for periodontal pathogens F. nucleatum and P. gingivalis by generating reactive oxygen species, which increases cell membrane permeability and destroys bacteria integrity to cause bacteria death. Meanwhile, PMT itself exhibited improved fibroblast viability and adhesion, with the PMT + light group revealing further activation of fibroblast cells, suggesting the coordinated action of Mg2+ and PBM effects. The underlying molecular mechanism might be the elevated gene expressions of Fibronectin 1, Col1a1, and Vinculin. In addition, the in vivo rat periodontitis model proved the superior therapeutic effects of PMT with laser illumination using micro-computed tomography analysis and histological staining, which presented decreased inflammatory cells, increased collagen production, and higher alveolar bone level in the PMT group. Our study sheds light on a promising strategy to fight periodontitis using versatile microspheres, which combine aPDT and PBM-assisted fibroblast activation functions.

Metal-organic framework-based nanoplatform enhance fibroblast activity to treat periodontitis.

After periodontal tissue injury, reconstruct soft tissue sealing around the tooth surface is of fundamental importance to treat periodontitis. Among multiple cell types, fibroblast plays a central role in reestablishing functional periodontium. To enhance fibroblast activity, a novel metal-organic framework-based nanoplatform is fabricated using mesoporous Prussian blue (MPB) nanoparticles to load baicalein (BA), named MPB-BA. Drug release test displayed sustained BA release of MPB-BA. Cell proliferation, transwell migration and wound healing tests revealed accelerated fibroblast proliferation and migration for the established MPB-BA nanoplatform. Moreover, vinculin immunofluorescence staining, western blot and quantitative real-time PCR analysis showed up-regulated vinculin protein and integrin α5 and integrin ß1 gene expressions for MPB-BA, suggesting improved cell adhesion. In addition, hematoxylin and eosin (H&E) and Masson trichromatic staining suggested superior anti-inflammatory and collagen fiber reconstruction effects for MPB-BA in a rat experimental periodontitis model in vivo. Our study may provide a promising strategy for the treatment of periodontitis.

Aspirin/PLGA coated 3D-printed Ti-6Al-4V alloy modulate macrophage polarization to enhance osteoblast differentiation and osseointegration.

Although titanium (Ti) and Ti-based alloy have been widely used as dental and orthopedic implant materials, its bioinertness hindered the rapid osseointegration. Therefore, it is recommended to acquire ideal topographic and chemical characteristics through surface modification methods. 3D printing is a delicate manufacture technique which possesses superior controllability and reproducibility. While aspirin serve as a well-established non-steroidal anti-inflammatory agent. Recently, the importance of immune system in regulating bone dynamics has attracted increasing attention. We herein superimposed the aspirin/poly (lactic-co-glycolic acid) (ASP/PLGA) coating on the 3D-printed Ti-6Al-4V surface with uniform micro-structure to establish the Ti64-M-ASP/PLGA substrate. Scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and contact angle test confirmed the successful fabrication of the Ti64-M-ASP/PLGA substrate, with increased wettability and sustained release pattern of ASP. Compared with the Ti64 base material, the Ti64-M-ASP/PLGA substrate showed enhanced M2 and depressed M1 genes and proteins expressions in macrophages. The novel Ti64-M-ASP/PLGA substrate also displayed enhanced osteoblast proliferation, adhesion, extracellular mineralization ability and osteogenic gene expressions when cultured with macrophage conditioned medium in vitro. Furthermore, rat femora implantation model was used for in vivo evaluation. After 4 weeks of implantation, push out test, micro-computed tomography (micro-CT) and histological analyses all confirmed the superior osseointegration capabilities of the Ti64-M-ASP/PLGA implant than the other groups. Our study revealed the synergistic role played by 3D-printed micro topography and immunoregulatory drug aspirin in promoting osteogenesis in vitro and accelerating osseointegration in vivo, thus providing a promising method for better modifying the implant surface. Graphical abstract.

Photothermal therapy with regulated Nrf2/NF-κB signaling pathway for treating bacteria-induced periodontitis.

Periodontitis is an inflammatory disease initiated by bacterial infection, developed by excessive immune response, and aggravated by high level of reactive oxygen species (ROS). Hence, herein, a versatile metal-organic framework (MOF)-based nanoplatform is prepared using mesoporous Prussian blue (MPB) nanoparticles to load BA, denoted as MPB-BA. The established MPB-BA nanoplatform serves as a shelter and reservoir for vulnerable immunomodulatory drug BA, which possesses antioxidant, anti-inflammatory and anti-bacterial effects. Thus, MPB-BA can exert its antioxidant, anti-inflammatory functions through scavenging intracellular ROS to switch macrophages from M1 to M2 phenotype so as to relieve inflammation. The underlying molecular mechanism lies in the upregulation of phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) to scavenge ROS and subsequently inhibit the nuclear factor kappa-B (NF-κB) signal pathway. Moreover, MPB-BA also exhibited efficient photothermal antibacterial activity against periodontal pathogens under near-infrared (NIR) light irradiation. In vivo RNA sequencing results revealed the high involvement of both antioxidant and anti-inflammatory pathways after MPB-BA application. Meanwhile, micro-CT and immunohistochemical staining of p-Nrf2 and p-P65 further confirmed the superior therapeutic effects of MPB-BA than minocycline hydrochloride. This work may provide an insight into the treatment of periodontitis by regulating Nrf2/NF-κB signaling pathway through photothermal bioplatform-assisted immunotherapy.

Activity, distribution, and abundance of methane-oxidizing bacteria in the near surface soils of onshore oil and gas fields.

Methane-oxidizing bacteria (MOB) have long been used as an important biological indicator for oil and gas prospecting, but the ecological characteristics of MOB in hydrocarbon microseep systems are still poorly understood. In this study, the activity, distribution, and abundance of aerobic methanotrophic communities in the surface soils underlying an oil and gas field were investigated using biogeochemical and molecular ecological techniques. Measurements of potential methane oxidation rates and pmoA gene copy numbers showed that soils inside an oil and gas field are hot spots of methane oxidation and MOB abundance. Correspondingly, terminal restriction fragment length polymorphism analyses in combination with cloning and sequencing of pmoA genes also revealed considerable differences in the methanotrophic community composition between oil and gas fields and the surrounding soils. Principal component analysis ordination furthermore indicated a coincidence between elevated CH4 oxidation activity and the methanotrophic community structure with type I methanotrophic Methylococcus and Methylobacter, in particular, as indicator species of oil and gas fields. Collectively, our results show that trace methane migrated from oil and gas reservoirs can considerably influence not only the quantity but also the structure of the methanotrophic community.