Porous Microspheres as Pathogen Traps for Sepsis Therapy: Capturing Active Pathogens and Alleviating Inflammatory Reactions.

Sepsis is a systemic inflammatory response syndrome caused by pathogen infection, while the current antibiotics mainly utilized in clinical practice to combat infection result in the release of pathogen-associated molecular patterns (PAMPs) in the body. Herein, we provide an innovative strategy for controlling sepsis, namely, capturing active pathogens by means of extracorporeal blood purification. Carbon nanotubes (CNTs) were modified with dimethyldiallylammonium chloride (DDA) through γ-ray irradiation-induced graft polymerization to confer a positive charge. Then, CNT-DDAs are blended with polyurethane (PU) to prepare porous microspheres using the electro-spraying method. The obtained microspheres with a pore diameter of 2 µm served as pathogen traps and are termed as PU-CNT-DDA microspheres. Even at a high flow rate of 50 mL·min-1, the capture efficiencies of the PU-CNT-DDAs for Escherichia coli and Staphylococcus aureus remained 94.7% and 98.8%, respectively. This approach circumvents pathogen lysis and mortality, significantly curtails the release of PAMPs, and hampers the production of pro-inflammatory cytokines. Therefore, hemoperfusion using porous PU-CNT-DDAs as pathogen traps to capture active pathogens and alleviate inflammation opens a new route for sepsis therapy.

Long-term, synergistic and high-efficient antibacterial polyacrylonitrile nanofibrous membrane prepared by "one-pot" electrospinning process.

Enhancing long-term antibacterial activity of membrane materials is an effective strategy to reduce biological contamination. Herein, we developed a long-term, synergistic antibacterial polyacrylonitrile (PAN) nanofiber membrane by a "one-pot" electrospinning process. In the reaction solution of PAN and N, N-dimethylformamide (DMF), silver-silicon dioxide nanoparticles (Ag@SiO2 NPs) are in-situ synthesized and stabilized using silane coupling agent; and [2-(methacryloyloxy)-ethyl] trimethylammonium chloride (MT) monomers are then in-situ cross-linked to obtain a polyquaternary ammonium salt (PMT). Subsequently, the casting solution is directly used to fabricate Ag@SiO2/PMT-PAN nanofibrous membrane (NFM) via electrospinning. The antibacterial activity, reusability, synergy effect and biological safety of the Ag@SiO2/PMT-PAN NFM are systematically investigated, and the synergistic antibacterial mechanism is also explored. Even at very low (0.3 wt%) content of silver, the Ag@SiO2/PMT-PAN NFM exhibits excellent antibacterial activity against E. coli (99%) and S. aureus (99%). Also, the antibacterial ability of the NFM remains the same level after three cycles of antibacterial processes with the efficient synergy effects of Ag@SiO2 and PMT components. When the Ag@SiO2/PMT-PAN contacts with bacteria, the PMT attracts and kills the bacteria through electrostatic action. The bacteria with damaged cell membranes are deposited on the nanofibrous membrane, which could greatly promote the release of Ag+ and further enhance the antibacterial activity. Moreover, L929 fibroblasts are co-cultured with the extract of 4 mg/mL Ag@SiO2/PMT-PAN for 5 days, which exhibits a low cytotoxicity with a cell proliferation ratio of 95%. This work opens new pathways for developing long-term effective and synergistic antibacterial nanofibrous membrane materials to prevent infections associated with biomedical equipment.

Facile and green approach towards biomass-derived hydrogel powders with hierarchical micro-nanostructures for ultrafast hemostasis.

Although a series of biomass-derived hemostats has been developed, the desire for green-prepared hemostatic materials with biosafety has not decreased. Herein, we constructed porous carboxymethyl chitosan/sodium alginate/Ca(OH)2 powders (PCSCPs) with suitable adaptability for instant control of irregular hemorrhage via a facile and green approach. By one-pot chemical crosslinking of carboxymethyl chitosan and sodium alginate, hydrogels were formed and immediately ionically cross-linked along with the generation of Ca(OH)2 to prepare PCSCPs. As hydrogel powders, PCSCPs with abundant hydrophilic carboxymethyl groups and porous hierarchically micro-nanostructures displayed a high water absorption ratio of over 1600%. The PCSCPs were confirmed with favorable hemocompatibility, non-cytotoxic effects and excellent degradability. Hemostasis assays in vitro showed that PCSCPs possessed an outstanding property of platelet activation and red blood cell aggregation. The PCSCPs effectively shortened the hemostatic time and blood loss to ca. 50% in rodent bleeding models compared with medical gauze and commercial chitosan-based hemostats. Furthermore, a mouse subcutaneous implantation model demonstrated an ignorable inflammation response and potential tissue repair capability of PCSCPs. It's believed that green-prepared and biomass-derived PCSCPs are feasible biomedical hemostatic materials in view of engineering and provide a promising platform to design hemostats in prehospital management and clinical settings.

Photoenhanced Dual-Functional Nanomedicine for Promoting Wound Healing: Shifting Focus from Bacteria Eradication to Host Microenvironment Modulation.

Pathogenic bacterial infection has become a serious medical threat to global public health. Once the skin has serious defects, bacterial invasion and the following chain reactions will be a thorny clinical conundrum, which takes a long time to heal. Although various strategies have been used to eradicate bacteria, the treatment which can simultaneously disinfect and regulate the infection-related host responses is rarely reported. Herein, inspired by the host microenvironment, a photoenhanced dual-functional nanomedicine is constructed (Hemin@Phmg-TA-MSN) for localized bacterial ablation and host microenvironment modulation. The "NIR-triggered local microthermal therapy" and positively charged surface endow the nanomedicine with excellent bacterial capture and killing activities. Meanwhile, the nanomedicine exhibits broad-spectrum reactive oxygen species (ROS) scavenging activity via the synergistic effect of hemin and tannic acid with photoenhanced electron and hydrogen transfers. Furthermore, the in vivo experiments demonstrate that the dual-functional nanomedicine not only presents robust bacterial eradication capability, but also triggers the oxidative stress and inflammatory microenvironment regulation. The work not only shows a facile and effective way for infected wound management but also provides a new horizon for designing novel and efficient anti-infection therapy shifting focus from bacteria treatment to host microenvironment modulation.

Smart Asymmetric Hydrogel with Integrated Multi-Functions of NIR-Triggered Tunable Adhesion, Self-Deformation, and Bacterial Eradication.

Multifunctional hydrogels acting as wound dressing have received extensive attention in soft tissue repair; however, it is still a challenge to develop a non-antibiotic-dependent antibacterial hydrogel that has tunable adhesion and deformation to achieve on-demand removal. Herein, an asymmetric adhesive hydrogel with near-infrared (NIR)-triggered tunable adhesion, self-deformation, and bacterial eradication is designed. The hydrogel is prepared by the crosslinking polymerization of N-isopropylacrylamide and acrylic acid, during the sedimentation of conductive PPy-PDA nanoparticles based on the polymerization of pyrrole (Py) and dopamine (DA). Due to the conversion capacity from NIR light into heat for PPy-PDA NPs, the formed temperature-sensitive hydrogel exhibits tissue adhesive as well as NIR-triggered tunable adhesion and self-deformation property, which can achieve an on-demand dressing refreshing. Systematically in vitro/in vivo antibacterial experiments indicate that the hydrogel shows excellent disinfection capability to both Gram-negative and Gram-positive bacteria. The in vivo experiments in a full-layer cutaneous wound model demonstrate that the hydrogel has a good treatment effect to promote wound healing. Overall, the asymmetric hydrogel with tunable adhesion, self-deformation, conductive, and photothermal antibacterial activity may be a promising candidate to fulfill the functions of adhesion on skin tissue, easy removing on-demand, and accelerating the wound healing process.

Reduced polydopamine nanoparticles incorporated oxidized dextran/chitosan hybrid hydrogels with enhanced antioxidative and antibacterial properties for accelerated wound healing.

Hydrogels with antioxidative and antibacterial properties have emerged as potential dressings for accelerated wound healing. Herein, a series of reduced polydopamine nanoparticles (rPDA NPs) incorporated oxidized dextran/chitosan hybrid hydrogels have been designed for wound healing due to their excellent antioxidative property and antibacterial activity. The physicochemical properties as well as the antioxidative activities of the hydrogels were carefully characterized. The results demonstrated rPDA NPs have better antioxidative activity than the untreated PDA NPs. And the rPDA NPs incorporated oxidized dextran/chitosan hybrid hydrogels had excellent antioxidative properties to protect cells against external oxidative stress. Besides, the hydrogels also showed antibacterial ability to protect the wound against infections. In vitro and in vivo investigations concluded that rPDA NPs incorporated oxidized dextran/chitosan hybrid hydrogels could be served as an effective dressing for accelerated wound healing.

Selective potassium uptake via biocompatible zeolite-polymer hybrid microbeads as promising binders for hyperkalemia.

Patients with chronic kidney disease are at high risk of hyperkalemia that is associated with various life-threatening complications. Treatments primarily rely on orally administered potassium binding agents, along with low curative effects and various side effects. Herein, direct serum potassium uptake was realized via zeolite-heparin-mimicking-polymer hybrid microbeads. The preparation process involved the synthesis of the heparin-mimicking polymer via the in situ cross-linking polymerization of acrylic acid and N-vinylpyrrolidone in polyethersulfone solution, the fabrication of microbeads via zeolite-mixing, electro-spraying and phase-inversion, and the subsequent aqueous-phase modifications based on ion-exchange and metal-leaching. An ultra-high (about 88%) amount of zeolite could be incorporated and well locked inside the polymer matrix. Potassium uptake capability was verified in water, normal saline and human serum, showing high selectivity and fast adsorption. The microbeads exhibited satisfying blood compatibility, negligible hemolysis ratio, prolonged clotting time, inhibited contact activation, and enhanced antifouling property toward serum proteins and cells. The proposed approach toward zeolite-heparin-mimicking-polymer hybrid microbeads provided a cheap, efficient and safe treatment protocol of hyperkalemia for the high-risk patients.

Positively-charged polyethersulfone nanofibrous membranes for bacteria and anionic dyes removal.

Given the complexity of pollutants in wastewater, development of facile and effective multifunctional materials, which can not only kill bacteria but also remove dyes from wastewater, is in high demand. Herein, a facile strategy for the preparation of positively-charged nanofibrous membranes (NFMs) is reported via the combination of electrospinning and in-situ cross-linked polymerization of poly ([2-(methacryloyloxy)-ethyl] trimethyl ammonium chloride) (PMETAC) in poly (ether sulfone) (PES) solution. The quaternary ammonium salt polymer of PMETAC enabled the NFMs with positive charge to kill bacteria and remove anionic dyes. The antibacterial tests including agar plate counting and live/dead staining indicate that the NFMs show strong antibacterial ability with bacterial killing ratios of nearly 99% for both Escherichia coli and Staphylococcus aureus, as well as remarkable recyclability towards killing bacteria. The dyes adsorption experiments show that the NFMs exhibit high adsorption capacity for anionic dyes up to 208 mg g-1 for Congo Red (CR) and good reusability toward CR. Impressively, the membrane adsorption column test indicates that the CR dye removal ratio is up to 100% for the first time, and that is still as high as 96.5% for the third time with a fresh dye solution. Given the above advantages, such fascinating NFMs may provide new perspectives in the exploitation of multifunctional membrane materials for complex water remediation.

Functionalized polyethersulfone nanofibrous membranes with ultra-high adsorption capacity for organic dyes by one-step electrospinning.

The adsorbents with high adsorption capacity are in urgent demand for water treatment because of the global freshwater crisis. In this work, the copolymer of acrylic acid and methyl methacrylate was synthesized at first, and subsequently blended with polyethersulfone (PES) with different mass ratios to prepare functionalized PES nanofibrous membranes via one-step electrospinning method. Benefiting from the abundant carboxyl groups, as well as the large specific surface area and high porosity, the nanofibrous membranes exhibited a maximum adsorption capacity of 2257.88 mg g-1 for methylene blue (MB) dyes, which was among the largest adsorption amount of those previously reported adsorbents. In addition, the adsorption process was systematically investigated under various conditions, including pH, initial MB concentrations and contact time. Meanwhile, the pseudo-second-order model and Langmuir isotherm model was very suitable to describe the adsorption kinetics and isotherm, respectively. Moreover, the nanofibrous membranes also exhibited excellent recyclability (81.45% after 5 cycles), high filtration-purification efficiency (above 99%, at a high flux of 100 mL min-1) and selective adsorption and separation abilities. These excellent performances endow the nanofibrous membranes with promising potential applications for dye wastewater treatment.