Precise antibacterial therapeutics based on stimuli-responsive nanomaterials.

Bacterial infection refers to the process in which bacteria invade, grow, reproduce, and interact with the body, ultimately causing a series of pathological changes. Nowadays, bacterial infection remains a significant public health issue, posing a huge threat to human health and a serious financial burden. In the post-antibiotic era, traditional antibiotics are prone to inducing bacterial resistance and difficulty in removing bacterial biofilm. In recent years, antibacterial therapy based on nanomaterials has developed rapidly. Compared with traditional antibiotics, nanomaterials effectively remove bacterial biofilms and rarely result in bacterial resistance. However, due to nanomaterials' strong permeability and effectiveness, they will easily cause cytotoxicity when they are not controlled. In addition, the antibacterial effect of non-responsive nanomaterials cannot be perfectly exerted since the drug release property or other antibacterial effects of these nano-materials are not be positively correlated with the intensity of bacterial infection. Stimuli-responsive antibacterial nanomaterials are a more advanced and intelligent class of nano drugs, which are controlled by exogenous stimuli and microenvironmental stimuli to change the dosage and intensity of treatment. The excellent spatiotemporal controllability enables stimuli-responsive nanomaterials to treat bacterial infections precisely. In this review, we first elaborate on the design principles of various stimuli-responsive antibacterial nanomaterials. Then, we analyze and summarizes the antibacterial properties, advantages and shortcomings of different applied anti-bacterial strategies based on stimuli-responsive nanomaterials. Finally, we propose the challenges of employing stimuli-responsive nanomaterials and corresponding potential solutions.

Characterization of Ferroelectric Al0.7Sc0.3N Thin Film on Pt and Mo Electrodes.

In the past decade, aluminum scandium nitride (AlScN) with a high Sc content has shown ferroelectric properties, which provides a new option for CMOS-process-compatible ferroelectric memory, sensors and actuators, as well as tunable devices. In this paper, the ferroelectric properties of Al0.7Sc0.3N grown on different metals were studied. The effect of metal and abnormal orientation grains (AOGs) on ferroelectric properties was observed. A coercive field of approximately 3 MV/cm and a large remanent polarization of more than 100 µC/cm2 were exhibited on the Pt surface. The Al0.7Sc0.3N thin film grown on the Mo metal surface exhibited a large leakage current. We analyzed the leakage current of Al0.7Sc0.3N during polarization with the polarization frequency, and found that the Al0.7Sc0.3N films grown on either Pt or Mo surfaces have large leakage currents at frequencies below 5 kHz. The leakage current decreases significantly as the frequency approaches 10 kHz. The positive up negative down (PUND) measurement was used to obtain the remanent polarization of the films, and it was found that the remanent polarization values were not the same in the positive and negative directions, indicating that the electrode material has an effect on the ferroelectric properties.

3D printing of MXene composite hydrogel scaffolds for photothermal antibacterial activity and bone regeneration in infected bone defect models.

The repair of infected bone defects with irregular shapes is still a challenge in clinical work. Infected bone defects are faced with several major concerns: the complex shapes of bone defects, intractable bacterial infection and insufficient osseointegration. To solve these problems, we developed a personalized MXene composite hydrogel scaffold GelMA/ß-TCP/sodium alginate (Sr2+)/MXene (Ti3C2) (GTAM) with photothermal antibacterial and osteogenic abilities by 3D printing. In vitro, GTAM scaffolds could kill both Gram-positive and Gram-negative bacteria by NIR irradiation due to the excellent photothermal effects of MXene. Furthermore, rat bone marrow mesenchymal stem cells were mixed into GTAM bioinks for 3D bioprinting. The cell-laden 3D printed GTAM scaffolds showed biocompatibility and bone formation ability depending on MXene, crosslinked Sr2+, and ß-TCP. In vivo, we implanted 3D printed GTAM scaffolds in S. aureus-infected mandible defects of rats with NIR irradiation. GTAM scaffolds could accelerate the healing of infection and bone regeneration, and play synergistic roles in antibacterial and osteogenic effects. This study not only provides a strategy for the precise osteogenesis of infected bone defects, but also broadens the biomedical applications of MXene photothermal materials.

Effective modification of photocatalytic and piezocatalytic performances for poly(heptazine imide) by carbon dots decoration.

As the high-crystalline phase of carbon nitride, poly(heptazine imide) (PHI) has attracted much attention in recent years, considering the more effective light absorption, better charge carrier behavior, and higher surface area of PHI compared with its counterpart with a melon structure that is commonly synthesized through thermal polymerization. Nevertheless, exploring effective strategies to further improve the performance of PHI is still highly desirable. In this work, it is revealed that the photocatalytic as well as piezocatalytic performances of PHI are greatly promoted by coupling with carbon dots (CDots) through a facile ultrasonication process. Detailed structure characterizations indicate that a very low content of CDots (0.05%) decoration can double the light absorbance and achieve the efficient separation and transfer of photogenerated charge carriers. The optimal photocatalytic hydrogen evolution rate of PHI/CDots is about 2.49 and 2.81 times that of PHI, under UV-Visible and visible light irradiation, respectively. Moreover, the piezocatalytic H2O2 generation and KMnO4 degradation activities of PHI/CDots are around 2 times that of PHI. The results obtained in this work provide references for the modification of PHI and may inspire new strategies for the design of highly efficient carbonaceous photocatalysts.

Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling.

BACKGROUND: The brain is in many ways an immunologically and pharmacologically privileged site because of the blood-brain barrier (BBB). But for chronic peripheral inflammation, inflammatory signals can be transmitted from the peripheral system into the central nervous system (CNS) through multiple channels and result in neuroinflammation. Leptomeningeal cells that form the BBB can trigger one signaling pathway by releasing cytokines to transmit inflammatory signals. Besides, the Janus kinase (JAK) family may have a certain function in the activation of leptomeninges. In the present study, we try to use coniferyl aldehyde (CA), a natural anti-inflammatory phenolic compound, to inhibit this inflammatory process and elucidate the underlying molecular mechanisms. RESULTS: Secretion of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) significantly increased after incubation with P. gingivalis. Moreover, TNF-α, IL-1ß, and IL-6 levels were upregulated, and the JAK2 signaling was enhanced in leptomeningeal cells in a conditioned medium from activated macrophages, which leads to the immune response in microglia. However, this inflammatory effect of leptomeningeal cells was reversed by CA administration, accompanied by the decreased immune response in microglia. The western blot assay revealed that JAK2 phosphorylation was suppressed in leptomeningeal cells treated with CA. CONCLUSIONS: This study demonstrates that activated macrophages by P. gingivalis markedly induce the release of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) from leptomeningeal cells, thereby activating the JAK2 signaling pathway and subsequently enhancing immune responses in microglia in the CNS. CA effectively inhibits the inflammatory effect of leptomeningeal cells via suppressing the JAK2 signaling pathway.

Porphyromonas gingivalis Infection Induces Amyloid-ß Accumulation in Monocytes/Macrophages.

Abnormal accumulation of amyloid-ß (Aß) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aß in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aß is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aß metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aß pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aß in the brain of patients with periodontitis. We showed that the increased expression of IL-1ß, AßPP770, CatB, Aß1-42, and Aß3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1ß, AßPP770, Aß1-42, and Aß3-42 in RAW264.7 cells. Aß3-42, but not Aß1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aß3-42 tended to be higher than that induced by Aß1-42. Additionally, the expression of AßPP770, CatB, Aß1-42, and Aß3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aß accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aß in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.

Tissue preservation through socket-shield technique and platelet-rich fibrin in immediate implant placement: A case report.

RATIONALE: In this report, a combination of socket-shield technique (SST) and platelet-rich fibrin (PRF) technique was used for immediate implant placement on a fractured central incisor. During the follow-up visit, cone beam computed tomography (CBCT) and clinical observation were used to evaluate the preservation outcome of peri-implant bone and gingiva. PATIENT CONCERNS: The patient was a 28-year-old healthy female patient who desired her fractured 21 to be replaced with an implant-supported single crown; the fractured 21 comprised a post-core crown with insufficient residual bone at the labial site. DIAGNOSIS: The root of 21 exhibited a complex root fracture; the labial portion of the alveolar ridge was thin (<1 mm) and partial ankylosis of the residual root was observed. INTERVENTIONS: Modified SST was applied to the labial portion of the residual root. The implant was placed immediately at the lingual site of the retained socket-shield root fragment; PRF was the placed in the gap between the root fragment and the implant. Final prosthodontic treatment was performed at 24 weeks after implant placement. OUTCOMES: Clinical examination and CBCT scanning at various follow-up visits time showed that the periodontal tissue was well- preserved. At 6 months after surgery, the average horizontal and vertical peri-implant bone resorption was 0.4 mm; a follow-up visit at 18 months post-loading indicated that peri-implant tissue was well preserved by the shield-technique and no significant peri-implant tissue resorption was displayed. LESSON SUBSECTIONS: In cases of anterior teeth with intact but insufficient residual alveolar ridge, the SST with PRF may be effective for preservation and maintenance of stable peri-implant tissue.