MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

Polyphenol-assisted albumin-based biomineralization nanocarriers with NIR-II-targeted photothermal performance towards broad-spectrum radical scavenging.

The oxidative stress is a state of imbalance in the body's oxidative balance, which can cause or worsen many diseases. Several studies have focused on the direct scavenging of free radicals, however, the strategy of precisely controlling antioxidant activities remotely and spatiotemporally has rarely been reported. Herein, we report a method inspired by the albumin-triggered biomineralization process with polyphenol-assisted strategy to prepare nanoparticles (TA-BSA@CuS) with NIR-II-targeted photo-enhanced antioxidant capacity. Systematic characterization demonstrated that the introduction of polyphenol (tannic acid (TA)) induced the formation of a CuO-doped heterogeneous structure and CuS nanoparticles. Compared with the TA-free CuS nanoparticles, TA-BSA@CuS exhibited excellent photothermal property in the NIR-II region, which is ascribed to the TA-induced Cu defects and doped CuO. Moreover, the photothermal property of CuS improved the broad-spectrum free radical scavenging efficiency of TA-BSA@CuS, and its H2O2 clearance rate increased by 47.3% under NIR-II irradiation. Meanwhile, TA-BSA@CuS exhibited low biological toxicity and intracellular free radical scavenging ability. Moreover, the excellent photothermal property of TA-BSA@CuS endowed it with good antibacterial ability. Therefore, we expect that this work will pave the way for the synthesis of polyphenolic compounds and the improvement in their antioxidant capacity.

Engineering Antioxidative Cascade Metal-Phenolic Nanozymes for Alleviating Oxidative Stress during Extracorporeal Blood Purification.

Oxidative stress is a compelling risk factor in chronic kidney diseases and is further aggravated for individuals during extracorporeal blood purification, ultimately leading to multiple complications. Herein, antioxidative cascade metal-phenolic nanozymes (metal-tannic acid nanozymes, M-TA NMs) are synthesized via metal ions-mediated oxidative coupling of polyphenols; then M-TA NMs engineered hemoperfusion microspheres (Cu-TAn@PMS) are constructed for alleviating oxidative stress. M-TA NMs show adjustable broad-spectrum antioxidative activities toward multiple reactive nitrogen and oxygen species (RNOS) due to the adjustable catalytic active centers. Importantly, M-TA NMs could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. Detailed structural and spectral analyses reveal that the existence of a transition metal could decrease the electronic energy band gaps of M-TA NMs to offer better electron transfers for RNOS scavenging. Notably, dynamic blood experiments demonstrate that Cu-TAn@PMS could serve as an antioxidant defense system for blood in hemoperfusion to scavenge intracellular reactive oxygen species (ROS) effectively even in the complex blood environment and further protect endogenous antioxidative enzymes and molecules. In general, this work developed antioxidative cascade nanozymes engineered microspheres with excellent therapeutic efficacy for the treatment of oxidative stress-related diseases, which exhibited potential for clinical blood purification and extended the biomedical applications of nanozymes.

Alloyed nanostructures integrated metal-phenolic nanoplatform for synergistic wound disinfection and revascularization.

New materials for combating bacteria-caused infection and promoting the formation of microvascular networks during wound healing are of vital importance. Although antibiotics can be used to prevent infection, treatments that can disinfect and accelerate wound healing are scarce. Herein, we engineer a coating that is both highly compatible with current wound dressing substrates and capable of simultaneously disinfecting and revascularizing wounds using a metal-phenolic nanoplatform containing an alloyed nanostructured architecture (Ag@Cu-MPNNC). The alloyed nanostructure is formed by the spontaneous co-reduction and catalytic disproportionation reaction of multiple metal ions on a foundation metal-phenolic supramolecular layer. This synergistic presence of metals greatly improves the antibacterial activity against both Gram-negative and Gram-positive pathogenic bacteria, while demonstrating negligible cytotoxicity to normal tissue. In infected rat models, the Ag@Cu-MPNNC could kill bacteria efficiently, promoting revascularization and accelerate wound closure with no adverse side effects in infected in vivo models. In other words, this material acts as a combination therapy by inhibiting bacterial invasion and modulating bio-nano interactions in the wound.

Clearance of methylene blue by CdS enhanced composite hydrogel materials.

Hydrogel material is considered to be one of the effective adsorbents widely used to remove organic pollutants. However, the poor mechanical properties of some hydrogels limit their applications. Herein, we prepared composite hydrogels, for which acrylic acid (AA) and acrylamide (AM) were cross-linked and polymerised as the main substrate with adsorption function, while CdS nanoparticles were mainly used as reinforced material. Scanning electron microscope (SEM), Fourier transform infrared spectrometer (FTIR), two-dimensional infrared vibrational echo spectroscopy (2D-IR), and thermal gravimetric analyzer (TGA) were used to determine the physical and chemical structures of the hydrogels. The effects of the composition of AA, AM, and CdS on the mechanical properties and adsorption behaviours of the hydrogels were investigated. Besides, based on the great potential photocatalytic application value for wastewater remediation under the sunlight of CdS, the influence of the CdS doping amount on the photocatalytic property was also studied. As a result, when the mass ratio of AA to AM was 5:5, the hydrogel showed the best mechanical properties, and along with increasing the amount of CdS, the mechanical strength of the hydrogel was significantly enhanced from 0.445 MPa to 1.014 MPa. Besides, the composite hydrogels showed high adsorption and photocatalytic degradation synergistic clearance effect on methylene blue. Thus, the introduction of CdS photocatalytic nanoparticles may be an efficient and economical approach towards bifunctional hydrogel materials with enhanced mechanical property and photocatalytic degradation for wastewater remediation.

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.

A self-cleaning zwitterionic nanofibrous membrane for highly efficient oil-in-water separation.

The oil and bacteria adhesion during membrane separation process brings great challenges to the operation costs and membrane service life. Meantime, the strong chemical corrosion in sewage seriously limits the durability of membrane as well. Herein, a facile strategy is developed for fabricating highly stable and efficient zwitterionic nanofibrous membrane (NFM) with self-cleaning feature via the combination of in-situ cross-linking of poly (sulfobetaine methacrylate) (PSBMA) and electrospun poly (ether sulfone) (PES) nanofibers. Owing to the introduction of zwitterionic functional groups, the PSBMA/PES NFM exhibits superior antifouling ability (over 3 cycles of crude oil fouling/self-cleaning and up to 7 days of bacteria adhesion/repelling tests). Moreover, the membrane also presents remarkable chemical stability in acidic, alkaline and salty environments; and exhibits excellent separation performance for both layered oil/water mixture and oil-in-water emulsion as well. Furthermore, the membrane is capable to remove bacteria during the continuous oil/water mixture separation. Overall, the proposed strategy provides a new perspective into developing long-term antifouling membrane materials for complicated oily wastewater remediation in various corrosive environments.

Green Fabrication of Tannic Acid-Inspired Magnetic Composite Nanoparticles toward Cationic Dye Capture and Selective Degradation.

An environmental strategy for developing sustainable materials presents an attractive prospect for wastewater remediation. Herein, a facile, green, and economical strategy is proposed to fabricate magnetic composite nanoparticles (NPs) toward cationic dye adsorption and selective degradation. To prepare the composite TiO2-PEI-TA@Fe3O4 NPs, tannic acid (TA) and polyethyleneimine (PEI) were first used to decorate Fe3O4 NPs at aqueous solution, and then TiO2 NPs were anchored onto the surfaces of Fe3O4 NPs based on the catecholamine chemistry. The chemical composition and microstructure of the obtained NPs were systematically characterized. The NPs not only exhibited adsorption ability for the cationic dye of methylene blue (MB) but also responded to ultraviolet light to selectively degrade the adsorbed MB, and the removal (adsorption and/or degradation) ratio for MB could reach 95%. In addition, cyclic experiments showed that the removal ratio of the composite NPs for MB could still be maintained more than 85% even after five cycles. Given by the above-mentioned advantages, such a green and facile strategy for combining the adsorption and degradation methods to construct magnetic nanocomposites exhibits potential applications in cationic dye selective removal and sustainable wastewater remediation.

Rationally designed magnetic poly(catechol-hexanediamine) particles for bacteria removal and on-demand biofilm eradication.

In this study, we proposed a green, facile and low-cost approach for the fabrication of multifunctional particles with robust bacteria removal capability and on-demand biofilm eradication activity. Based on mussel-inspired coating of catechol and hexanediamine on Fe3O4 in aqueous solution, magnetic poly(catechol-hexanediamine) particles (Fe3O4@HDA) were prepared successfully in 1 h, at room temperature. Microbiological experiments demonstrated the Fe3O4@HDA particles could capture bacteria in water efficiently. Meanwhile, with an integration of magnetic response property and near-infrared-triggered photothermal bactericidal activity, the Fe3O4@HDA particles showed a high potential for biofilm targeting and in-situ eradication. We believe that the rationally designed magnetic poly(catechol-hexanediamine) particles could extend the applications of smart antimicrobial agents to industrial fields such as water disinfection and biofouling clean-up.

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.

General Method for Synthesizing Transition-Metal Phosphide/N-Doped Carbon Nanomaterials for Hydrogen Evolution.

Applications of effective and steady metal catalysts for the hydrogen evolution reaction (HER) via electrolysis of water have a huge potential to relax energy crisis and reduce carbon dioxide emission. Herein, we design a simple, facile, and general approach for the synthesis of a series of transition-metal phosphide nanoparticles embedded in N-doped carbon (NC) nanomaterials using metal salts, abundantly available hexamethylene diamine tetra(methyl phosphonic acid), and urea as precursors. The resultant transition-metal phosphide nanoparticles can serve as high-efficiency and steady HER catalysts. Particularly, when the current density is 10 mA cm-2, the overpotentials of the obtained RhP2@NC are 30, 85, and 70 mV in acid (0.5 M H2SO4), neutral (1 M PBS), and alkaline (1 M KOH) solutions, respectively. Besides, the RhP2@NC exhibits good stability after 10 h in aforementioned solutions. More importantly, it is suited to fabricate other transition-metal phosphide nanoparticles/NC heterostructures by this synthetic strategy. The obtained CoP@NC, FeP@NC, Ni2P@NC, and Cu3P@NC also show relatively high efficiency for HER. Hence, the versatile synthesis strategy opens a new route for the research and fabrication of transition-metal phosphide-based catalysts for HER.

Codeposition of Polydopamine and Zwitterionic Polymer on Membrane Surface with Enhanced Stability and Antibiofouling Property.

Although abundant works have been developed in mussel-inspired antifouling coatings, most of them suffer from poor chemical stability, especially in a strongly alkaline environment. Herein, we report a robust one-step mussel-inspired method to construct a highly chemical stable and excellent antibiofouling membrane surface coating with a highly efficient codeposition of polydopamine (PDA) with zwitterionic polymer. In the study, PDA and polyethylenimine-quaternized derivative (PEI-S) are codeposited on the surface of poly(ether sulfone) (PES) ultrafiltration membrane in water at room temperature. In contrast to individual PDA coating, the obtained PDA/PEI-S coating exhibits excellent chemical stability even in a strongly alkaline environment owing to the cross-linking and unexpected cation-π interaction between the PEI-S and PDA. Thanks to the introduction of PEI-S, systematic protein adsorption tests and bacteria adhesion experiments demonstrated that the surfaces could prevent bovine serum fibrinogen and lysozyme adsorption and could reduce Gram-positive bacteria S. aureus and Gram-negative bacteria E. coli adhesion. Benefiting from the versatile functionality of PDA, the proposed strategy is not limited to PES membrane surface but also others such as poly(ethylene terephthalate) sheets and commercial polypropylene microfiltration membranes. Overall, this work enriches the exploration of a remarkable coating with enhanced stability and excellent antifouling property via a facile, robust, and material-independent approach to modifying the membrane surface.

Multifunctional negatively-charged poly (ether sulfone) nanofibrous membrane for water remediation.

Multifunctional materials, which can effectively and simultaneously remove various water-soluble contaminants like dyes and heavy metal ions, and separate oil from water, are urgent to meet increasing challenges on wastewater remediation. Herein, a cross-linked poly (acrylic acid) (PAA) modified poly (ether sulfone) nanofibrous membrane (NFM) was fabricated by a facile in-situ pre-reaction followed by electrospinning. The as-prepared NFM showed excellent hydrophilicity and underwater lipophobicity, therefore expressed excellent water permeability with high water flux (about 5142 L m2 h-1). As a result, under solely driven by gravity, the NFM was capable to separate emulsified oil/water emulsion and a wide range of oil/water mixtures. Moreover, repeating separation tests indicated that the NFM had great long-term sustainability even after ten separation cycles. In addition, due to the introduction of PAA and the large surface-to-volume ratio, the NFM also expressed rapid adsorption capacity for cationic dyes as well as heavy metal ions; thus could simultaneously remove these contaminants during the oil/water separation process. Furthermore, the NFM could be also decorated by Ag NPs to endow the membranes with remarkable antibacterial ability against both E. coli and S. aureus. Our findings strongly suggested that the multifunctional NFM may have great potential in treating complicated wastewater.

Photo-responsive membrane surface: Switching from bactericidal to bacteria-resistant property.

In this paper, a photo-responsive bactericidal and bacteria-resistant membrane was successfully prepared via the integration of atom transfer radical polymerization (ATRP) and click chemistry. Azide-functionalized polycationic poly (N, N-dimethyl-N-(2-(methacryloyloxy)ethyl)-N-((2-nitrobenzyl)oxy)-2-oxoethanaminium bromide) (PDMAEMA-NBE) was synthesized by ATRP. Then, the PDMAEMA-NBE was clicked on alkynyl-functionalized polyethersulfone (PES) membrane surface, and proved by X-ray photoelectron spectrometer (XPS). Upon UV irradiation, the polycationic surface would switch to polyzwitterionic one. Before and after the irradiation, the zeta potentials of the surface altered from +14.7 to -3.8mV, and the water contact angle decreased from 64.0° to 52.7°. The polycationic surface exhibited excellent bactericidal property and the dead bacteria could detach from the polyzwitterionic surface induced by the subsequent UV irradiation. It demonstrated that the designing of photo-responsive membrane surface could be a new strategy for antibacterial adhesion.

Integrating zwitterionic polymer and Ag nanoparticles on polymeric membrane surface to prepare antifouling and bactericidal surface via Schiff-based layer-by-layer assembly.

Development of antibacterial membranes is strongly desired for biomedical applications. Herein, we integrated antifouling and bactericidal properties on polymeric membrane surface via Schiff-based layer-by-layer (LbL) assembly. Zwitterionic polymers bearing plentiful amino groups (based on polyethylenimine (PEI) and sulfobetaine methacrylate (SBMA), and termed as PEI-SBMA) were utilized to prepare an antifouling membrane surface; then robust wide-spectrum bactericidal Ag nanoparticles (Ag NPs) were in situ generated on the surface. The as-prepared zwitterionic polymer surface showed excellent resistance to protein adsorption and bacterial adhesion. The Ag NPs could be tightly and uniformly distributed on the membrane surface by the chelation of PEI-SBMA, and endowed the membrane with bactericidal activity. Meanwhile, the Ag NPs loaded membrane could effectively resist bacterial attachment for a long time, even though the bactericidal activity lost. The proposed bactericidal and antifouling membrane was flexible, versatile and could be large-scale preparation; and this strategy would have great potential to be widely used to avoid undesired bacterial contamination of biomedical implants or biological devices.

Multi-responsive drug release from hydrogen-bonding multilayers containing PEGylated nanoparticles and azobenzenes.

Using PEGylated nanoparticles and light-sensitive azobenzenes, a multicolor fluorescence layer-by-layer film loading drug has been constructed based on hydrogen bonding. The multilayer film exhibited multi-responsive drug release properties.