Eradicating Multidrug‐Resistant Bacteria Rapidly Using a Multi Functional g‐C3N4@ Bi2S3 Nanorod Heterojunction with or without Antibiotics

Wound infections caused by multidrug‐resistant (MDR) bacteria are hard to treat because of tolerance to existing antibiotics, repeated infection, and concomitant inflammation. Herein, zinc atom–doped g‐C₃N₄ and Bi₂S₃ nanorod heterojunctions (CN–Zn/BiS) are investigated for disinfection under near‐infrared light (NIR). The photocatalysis of CN–Zn/BiS is enhanced because of efficient charge separation during the interface electron field and increased oxygen adsorption capacity. Then, 99.2% antibacterial efficiency is shown toward methicillin‐resistant Staphylococcus aureus (MRSA) and 99.6% toward Escherichia coli under 10 min NIR irradiation. Meanwhile, a strategy for the combination of lapsed β‐lactam antibiotics with the photosensitizer CN–Zn/BiS is provided to kill MRSA by NIR without observable resistance, suggesting an approach to solve the problem of bacterial infection with NIR light penetrability and for exploiting new anti‐infection methods. The CN–Zn/BiS nanocomposite can also regulate genes and the inflammatory response through inflammatory factors (IL‐1β, IL‐6, TNF‐α, and iNOS) in vivo to accelerate tissue regeneration and thereby promote wound healing.     

Self‐Assembly of Antimicrobial Peptides on Gold Nanodots: Against Multidrug‐Resistant Bacteria and Wound‐Healing Application

Photoluminescent gold nanodots (Au NDs) are prepared via etching and codeposition of hybridized ligands, an antimicrobial peptide (surfactin; SFT), and 1‐dodecanethiol (DT), on gold nanoparticles (≈3.2 nm). As‐prepared ultrasmall SFT/DT–Au NDs (size ≈2.5 nm) are a highly efficient antimicrobial agent. The photoluminescence properties and stability as well as the antimicrobial activity of SFT/DT–Au NDs are highly dependent on the density of SFT on Au NDs. Relative to SFT, SFT/DT–Au NDs exhibit greater antimicrobial activity, not only to nonmultidrug‐resistant bacteria but also to the multidrug‐resistant bacteria. The minimal inhibitory concentration values of SFT/DT–Au NDs are much lower (>80‐fold) than that of SFT. The antimicrobial activity of SFT/DT–Au NDs is mainly due to the synergistic effect of SFT and DT–Au NDs on the disruption of the bacterial membrane. In vitro cytotoxicity and hemolysis analyses have revealed superior biocompatibility of SFT/DT–Au NDs than that of SFT. Moreover, in vivo methicillin‐resistant S. aureus–infected wound healing studies in rats show faster healing, better epithelialization, and are more efficient in the production of collagen fibers when SFT/DT–Au NDs are used as a dressing material. This study suggests that the SFT/DT–Au NDs are a promising antimicrobial candidate for preclinical applications in treating wounds and skin infections.     

Physical Double‐Network Hydrogel Adhesives with Rapid Shape Adaptability,Fast Self‐Healing,Antioxidant and NIR/pH Stimulus‐Responsiveness for Multidrug‐Resistant Bacterial Infection and Removable Wound Dressing

Developing physical double‐network (DN) removable hydrogel adhesives with both high healing efficiency and photothermal antibacterial activities to cope with multidrug‐resistant bacterial infection, wound closure, and wound healing remains an ongoing challenge. An injectable physical DN self‐healing hydrogel adhesive under physiological conditions is designed to treat multidrug‐resistant bacteria infection and full‐thickness skin incision/defect repair. The hydrogel adhesive consists of catechol–Fe³⁺ coordination cross‐linked poly(glycerol sebacate)‐co‐poly(ethylene glycol)‐g‐catechol and quadruple hydrogen bonding cross‐linked ureido‐pyrimidinone modified gelatin. It possesses excellent anti‐oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self‐healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing‐assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin‐resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full‐thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on‐demand dissolvable and antioxidant physical double‐network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.     

Layer‐By‐Layer Coating of Aminocellulose and Quorum Quenching Acylase on Silver Nanoparticles Synergistically Eradicate Bacteria and Their Biofilms

The emergence of antibiotic‐resistant bacteria and the failure of the existing antibacterial therapeutics call for development of novel treatment strategies. Furthermore, the formation of bacterial biofilms restricts drug penetration and efficiency, causing life‐threatening infections. Bacterial attachment and biofilm formation are regulated by the cell‐to‐cell communication phenomenon called quorum sensing (QS). In this work, antimicrobial silver nanoparticles (AgNPs) are decorated in a layer‐by‐layer fashion with the oppositely charged aminocellulose (AM) and acylase to generate hybrid nanoentities with enhanced antibacterial and antibiofilm activities as well as reduced cytotoxicity. Acylase, a quorum‐quenching enzyme that degrades the QS signals in the extracellular environment of bacteria, disrupts the bacterial QS process and together with the bactericidal AM synergistically lowers fourfold the minimum inhibitory concentration of the AgNPs templates toward Gram‐negative Pseudomonas aeruginosa (P. aeruginosa). The hybrid nanoparticles in eightfold‐lower concentration than the AgNPs inhibit 45% of the QS‐regulated virulence factors produced by the reporter Chromobacterium violaceum bacterial strain and reduce by 100% the P. aeruginosa biofilm formation. Moreover, the sequential deposition of antibacterial/antibiofilm active and biocompatible biopolymers onto the AgNPs allows the engineering of safe nanomaterials that do not affect the viability of human cells.     

Controlled Release of LL‐37‐Derived Synthetic Antimicrobial and Anti‐Biofilm Peptides SAAP‐145 and SAAP‐276 Prevents Experimental Biomaterial‐Associated Staphylococcus aureus Infection

The present study aims to develop an implant coating releasing novel antimicrobial agents to prevent biomaterial‐associated infections. The LL‐37‐derived synthetic antimicrobial and anti‐biofilm peptides (SAAP)‐145 and SAAP‐276 exhibit potent bactericidal and anti‐biofilm activities against clinical and multidrug‐resistant Staphylococcus aureus strains by rapid membrane permeabilization, without inducing resistance. Injection of SAAP‐145, but not SAAP‐276, along subcutaneous implants in mice reduces S. aureus implant colonization by approximately 2 log, but does not reduce bacterial numbers in surrounding tissue. To improve their efficacy, SAAP‐145 and SAAP‐276 are incorporated in a polymer–lipid encapsulation matrix (PLEX) coating, providing a constant release of 0.6% daily up to 30 d after an initial burst release of >50%. In a murine model for biomaterial‐associated infection, SAAP‐145‐PLEX and SAAP‐276‐PLEX coatings significantly reduce the number of culture positive implants and show ≥3.5 and ≥1.5 log lower S. aureus implant and tissue colonization, respectively. Interestingly, these peptide coatings are also highly effective against multidrug‐resistant S. aureus, both reducing implant colonization by ≥2 log. SAAP‐276‐PLEX additionally reduces tissue colonization by 1 log. Together, the peptide‐releasing PLEX coatings hold promise for further development as an alternative to coatings releasing conventional antibiotics to prevent biomaterial‐associated infections.     

Magnetically Driven Silver‐Coated Nanocoils for Efficient Bacterial Contact Killing

The increasing threat of multidrug‐resistant bacterial strains against conventional antibiotic therapies represents a significant worldwide health risk and intensifies the need for novel antibacterial treatments. In this work, an effective strategy to target and kill bacteria using silver‐coated magnetic nanocoils is reported. The coil palladium (Pd) nanostructures are obtained by electrodeposition and selective dealloying, and subsequently coated with nickel (Ni) and silver (Ag) for magnetic manipulation and antibacterial properties, respectively. The efficiency of the nanocoils is tested in the treatment of Gram‐negative Escherichia coli (E. coli) and Gram‐positive methicillin‐resistant Staphylococcus aureus (S. aureus), both of which represent the leading multidrug‐resistant bacterial pathogens. The nanocoils show highly effective bacterial killing activity at low concentrations and in relatively short durations of treatment time. Three different investigation techniques, LIVE/DEAD assay, colony‐forming unit counting, and scanning electron microscope, reveal that the antibacterial activity is a result of bacterial membrane damage caused by direct contact with the nanocoil. The low cytotoxicity toward fibroblast cells along with the capability of precise magnetic locomotion makes the proposed nanocoil an ideal candidate to combat multidrug‐resistant bacteria in the field of biomedical and environmental applications.     

Eradication of Multidrug‐Resistant Staphylococcal Infections by Light‐Activatable Micellar Nanocarriers in a Murine Model

Bacterial infections are mostly due to bacteria in their biofilm mode‐of‐growth, making them recalcitrant to antibiotic penetration. In addition, the number of bacterial strains intrinsically resistant to available antibiotics is alarmingly growing. This study reports that micellar nanocarriers with a poly(ethylene glycol) shell fully penetrate staphylococcal biofilms due to their biological invisibility. However, when the shell is complemented with poly(β‐amino ester), these mixed‐shell micelles become positively charged in the low pH environment of a biofilm, allowing not only their penetration but also their accumulation in biofilms without being washed out, as do single‐shell micelles lacking the pH‐adaptive feature. Accordingly, bacterial killing of multidrug resistant staphylococcal biofilms exposed to protoporphyrin IX‐loaded mixed‐shell micelles and after light‐activation is superior compared with single‐shell micelles. Subcutaneous infections in mice, induced with vancomycin‐resistant, bioluminescent staphylococci can be eradicated by daily injection of photoactivatable protoporphyrin IX‐loaded, mixed‐shell micelles in the bloodstream and light‐activation at the infected site. Micelles, which are not degraded by bacterial enzymes in the biofilm, are degraded in the liver and spleen and cleared from the body through the kidneys. Thus, adaptive micellar nanocarriers loaded with light‐activatable antimicrobials constitute a much‐needed alternative to current antibiotic therapies.     

Injectable Self‐Healing Antibacterial Bioactive Polypeptide‐Based Hybrid Nanosystems for Efficiently Treating Multidrug Resistant Infection,Skin‐Tumor Therapy,and Enhancing Wound Healing

The surgical procedure in skin‐tumor therapy usually results in cutaneous defects, and multidrug‐resistant bacterial infection could cause chronic wounds. Here, for the first time, an injectable self‐healing antibacterial bioactive polypeptide‐based hybrid nanosystem is developed for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The multifunctional hydrogel is successfully prepared through incorporating monodispersed polydopamine functionalized bioactive glass nanoparticles (BGN@PDA) into an antibacterial F127‐ε‐Poly‐L‐lysine hydrogel. The nanocomposites hydrogel displays excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo. The nanocomposites hydrogel also demonstrates outstanding photothermal performance with (near‐infrared laser irradiation) NIR irradiation, which could effectively kill the tumor cell (>90%) and inhibit tumor growth (inhibition rate up to 94%) in a subcutaneous skin‐tumor model. In addition, the nanocomposites hydrogel effectively accelerates wound healing in vivo. These results suggest that the BGN‐based nanocomposite hydrogel is a promising candidate for skin‐tumor therapy, wound healing, and anti‐infection. This work may offer a facile strategy to prepare multifunctional bioactive hydrogels for simultaneous tumor therapy, tissue regeneration, and anti‐infection.     

Dual‐Mechanism Antimicrobial Polymer–ZnO Nanoparticle and Crystal Violet‐Encapsulated Silicone

The prevalence of healthcare‐associated infection caused by multidrug‐resistant bacteria is of critical concern worldwide. It is reported on the development of a bactericidal surface prepared by use of a simple, upscalable, two‐step dipping strategy to incorporate crystal violet and di(octyl)­phosphinic‐ acid‐capped zinc oxide nanoparticles into medical grade silicone, as a strategy to reduce the risk of infection. The material is characterized by UV–vis absorbance spectroscopy, X‐ray photoelectron spectroscopy (XPS), inductively coupled plasma‐optical emission spectroscopy (ICP‐OES) and transmission electron microscopy (TEM) and confirmed the incorporation of the ZnO nanoparticles in the polymer. The novel system proves to be a highly versatile bactericidal material when tested against both Staphylococcus aureus and Escherichia coli, key causative micro‐organisms for hospital‐acquired infection (HAI). Potent antimicrobial activity is noted under dark conditions, with a significant enhancement exhibits when the surfaces are illuminated with a standard hospital light source. This polymer has the potential to decrease the risk of HAI, by killing bacteria in contact with the surface.     

Multifunctional Nano‐Biointerfaces: Cytocompatible Antimicrobial Nanocarriers from Stabilizer‐Free Cubosomes

The rational design of alternative antimicrobial materials with reduced toxicity toward mammalian cells is highly desired due to the growing occurrence of bacteria resistant to conventional antibiotics. A promising approach is the design of lipid‐based antimicrobial nanocarriers. However, most of the commonly used polymer‐stabilized nanocarriers are cytotoxic. Herein, the design of a novel, stabilizer‐free nanocarrier for the human cathelicidin derived antimicrobial peptide LL‐37 that is cytocompatible and promotes cell proliferation for improved wound healing is reported. The nanocarrier is formed through the spontaneous integration of LL‐37 into novel, stabilizer‐free glycerol mono‐oleate (GMO)‐based cubosomes. Transformations in the internal structure of the cubosomes from Pn3m to Im3m‐type and eventually their transition into small vesicles and spherical micelles are demonstrated upon the encapsulation of LL‐37 into their internal bicontinuous cubic structure using small angle X‐ray scattering, cryogenic transmission electron microscopy, and light scattering techniques. Additional in vitro biological assays show the antimicrobial activity of the stabilizer‐free nano‐objects on a variety of bacteria strains, their cytocompatibility, and cell‐proliferation enhancing effect. The results outline a promising strategy for the comprehensive design of antimicrobial, cytocompatible lipid nanocarriers for the protection and delivery of bioactive molecules with potential for application as advanced wound healing materials.     

Silver‐Infused Porphyrinic Metal–Organic Framework: Surface‐Adaptive,On‐Demand Nanoplatform for Synergistic Bacteria Killing and Wound Disinfection

The fabrication of functional nanoplatforms for combating multidrug‐resistant bacteria is of vital importance. Among them, silver nanoparticles (Ag NPs) have shown an antibacterial effect; however, the remainder cores of Ag NPs after use might have a toxic effect on humans. Thus, Ag ions based materials have been fabricated to substitute Ag NPs for antibacterial applications. Nevertheless, the always‐on release state leads to the low biocompatibility, which limits their biomedical applications. In addition, the single effect also restricts their antibacterial ability. Herein, a powerful surface‐adaptive, on‐demand antimicrobial nanoplatform is fabricated by coating hyaluronic acid (HA) on Ag ions loaded photosensitive metal‐organic frameworks to exhibit a strong synergistic effect. The nanoplatform shows good biocompatibility with nontargeted cells, as negatively charged HA can prevent the release of Ag ions. While in the presence of targeted bacteria, the secreted hyaluronidase can degrade HA on the nanoplatform and produce positively charged nanoparticles, which display increased affinity to bacteria and show a strong synergistic antibacterial effect owing to the released Ag ions and generated reactive oxygen species under visible light irradiation. Importantly, due to the outstanding on‐demand antimicrobial performance, the nanoplatform also shows great effects on treating multidrug‐resistant bacteria infected wounds in mice models.     

Polycationic Synergistic Antibacterial Agents with Multiple Functional Components for Efficient Anti‐Infective Therapy

Multifunctional antibacterial photodynamic therapy is a promising method to combat regular and multidrug‐resistant bacteria. In this work, eosin Y (EY)‐based antibacterial polycations (EY‐QEGED? R, R = ? CH₃ or ? C₆H₁₃) with versatile types of functional components including quaternary ammonium, photosensitizer, primary amine, and hydroxyl species are readily synthesized based on simple ring‐opening reactions. In the presence of light irradiation, such antibacterial polymers exhibit high antibacterial efficiency against both Escherichia coli and Staphylococcus aureus. In particular, EY‐QEGED? R elicits a remarkable synergistic antibacterial activity owing to the combined photodynamic and quaternary ammonium antibacterial effects. Due to its rich primary amine groups, EY‐QEGED? R also can be readily coated on different substrates, such as glass slides and nonwoven fabrics via an adhesive layer of polydopamine. The resultant surface coating of EY‐QEGED? CH₃ (s‐EY‐QEGED? CH₃) produces excellent in vitro antibacterial efficacy. The plentiful hydroxyl groups impart s‐EY‐QEGED? CH₃ with potential antifouling capability against dead bacteria. The antibacterial polymer coatings also demonstrate low cytotoxicity and good hemocompatibility. More importantly, s‐EY‐QEGED? CH₃ significantly enhances in vivo therapeutic effects on an infected rat model. The present work provides an efficient strategy for the rational design of high‐performance antibacterial materials to fight biomedical device‐associated infections.     

Rapid Sterilization and Accelerated Wound Healing Using Zn2+ and Graphene Oxide Modified g‐C3N4 under Dual Light Irradiation

Wound healing is affected by bacterial infection and related inflammation, cell proliferation and differentiation, and tissue remodeling. Current antibiotics therapy cannot promote wound healing and kill bacteria at the same time. Herein, hybrid nanosheets of g‐C₃N₄‐Zn²⁺@graphene oxide (SCN‐Zn²⁺@GO) are prepared by combining Zn²⁺ doped sheet‐like g‐C₃N₄ with graphene oxide via electrostatic bonding and π–π stacking interactions to assist wound healing and kill bacteria simultaneously by short‐time exposure to 660 and 808 nm light. The gene expressions of matrix metalloproteinase‐2, type I collagen, type III collagen, and interleukin β in fibroblasts are regulated by GO and released Zn²⁺, which can accelerate wound healing. Co‐irradiation produces an antibacterial ratio over 99.1% within a short time because of the synergistic effects of both photodynamic antibacterial and photothermal antibacterial treatments. The hyperthermia produced by 808 nm light illumination can weaken the bacterial activity. And these bacteria can be easily killed by membrane destruction, protein denaturation, and disruption of bacterial metabolic pathways due to reactive oxygen species produced under 660 nm light irradiation. This strategy of Zn²⁺ and GO modification can increase the antibacterial efficacy of SCN and accelerate wound healing at the same time, which makes this SCN‐Zn²⁺@GO be very promising in bacteria‐infected wound healing therapy.     

Quaternized Silicon Nanoparticles with Polarity‐Sensitive Fluorescence for Selectively Imaging and Killing Gram‐Positive Bacteria

With the emergence of antibiotic resistance, developing new antibiotics and therapies for combating bacterial infections is urgently needed. Herein, a series of quaternized fluorescent silicon nanoparticles (SiNPs) are facilely prepared by the covalent reaction between amine‐functionalized SiNPs and carboxyl‐containing N‐alkyl betaines. It is found that the bactericidal efficacy of these quaternized SiNPs increases with the length of the N‐alkyl chain, and SiNPs conjugated with N,N‐dimethyl‐N‐octadecylbetaine (BS‐18), abbreviated as SiNPs‐C₁₈, show the best antibacterial effect, whose minimum inhibitory concentrations for Gram‐positive bacteria are 1–2 μg mL^?1. In vivo tests further confirm that SiNPs‐C₁₈ have excellent antibacterial efficacy and greatly reduce bacterial load in the infectious sites. The SiNPs‐C₁₈ exhibit low cytotoxicity toward mammalian cells (including normal liver and lung cells, red blood cells, and macrophages), enabling them to be useful for clinical applications. Besides, the quaternized SiNPs exhibit polarity‐dependent fluorescence emission property and can selectively image Gram‐positive bacteria, thereby providing a simple method to successfully differentiate Gram‐positive and Gram‐negative bacteria. The present work represents the first example that successfully turns fluorescent SiNPs into metal‐free NP‐based antibiotics with simultaneous bacterial imaging and killing capability, which broadens the applications of fluorescent SiNPs and advances the development of novel antibacterial agents.     

pH Switchable Nanoplatform for In Vivo Persistent Luminescence Imaging and Precise Photothermal Therapy of Bacterial Infection

Photothermal therapy (PTT) is one of the most promising approaches to combat multidrug‐resistant bacteria with less potential to induce resistance and systemic toxicity. However, uncontrollable distribution of photothermal agents leads to lethal temperatures for normal cells, and failure to offer timely and effective antibacterial stewardship. A pH switchable nanoplatform for persistent luminescence imaging‐guided precise PTT to selectively destroy only pathological cells while protecting nearby normal cells in bacterial infected microenvironment is shown. The PLNP@PANI‐GCS is fabricated by grafting polyaniline (PANI) and glycol chitosan (GCS) onto the surface of persistent luminescence nanoparticles (PLNPs). It takes advantage of the long persistent luminescence of PLNPs to realize autofluorescence‐free imaging, the pH‐dependent light–heat conversion property of PANI to get a stronger photothermal effect at pH 6.5 than pH 7.4, and the pH environment responsive surface charge transition of GCS. Consequently, PLNP@PANI‐GCS enables effective response to bacterial‐infected acid region and electrostatic bonding to bacteria in vivo, ensuring the spatial accuracy of near‐infrared light irradiation and specific heating directly to bacteria. In vivo imaging‐guided PTT to bacterial infection abscess shows effective treatment. PLNP@PANI‐GCS has great potential in treating multidrug‐resistant bacterial infection with low possibility of developing microbial drug resistance and little harm to normal cells.     

Antimicrobial Gallium‐Doped Phosphate‐Based Glasses

Novel quaternary gallium‐doped phosphate‐based glasses (1, 3, and 5 mol % Ga₂O₃) were synthesized using a conventional melt quenching technique. The bactericidal activities of the glasses were tested against both Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus, and Clostridium difficile) bacteria. Results of the solubility and ion release studies showed that these glass systems are unique for controlled delivery of Ga³⁺. ⁷¹Ga NMR measurements showed that the gallium is mostly octahedrally coordinated by oxygen atoms, whilst FTIR spectroscopy provided evidence for the presence of a small proportion of tetrahedral gallium in the samples with the highest gallium content. FTIR and Raman spectra also afford an insight into the correlation between the structure and the observed dissolution behavior via an understanding of the atomic‐scale network bonding characteristics. The results confirmed that the net bactericidal effect was due to Ga³⁺, and a concentration as low as 1 mol % Ga₂O₃ was sufficient to mount a potent antibacterial effect. The dearth of new antibiotics in development makes Ga³⁺ a potentially promising new therapeutic agent for pathogenic bacteria including MRSA and C. difficile.     

Study of Configuration Differentia and Highly Efficient,Deep‐Blue,Organic Light‐Emitting Diodes Based on Novel Naphtho[1,2‐d]imidazole Derivatives

Two novel naphtho[1,2‐d]imidazole derivatives are developed as deep‐blue, light‐emitting materials for organic light‐emitting diodes (OLEDs). The 1H‐naphtho[1,2‐d]imidazole based compounds exhibit a significantly superior performance than the 3H‐naphtho[1,2‐d]imidazole analogues in the single‐layer devices. This is because they have a much higher capacity for direct electron‐injection from the cathode compared to their isomeric counterparts resulting in a ground‐breaking EQE (external quantum efficiency) of 4.37% and a low turn‐on voltage of 2.7 V, and this is hitherto the best performance for a non‐doped single‐layer fluorescent OLED. Multi‐layer devices consisting of both hole‐ and electron‐transporting layers, result in identically excellent performances with EQE values of 4.12–6.08% and deep‐blue light emission (Commission Internationale de l'Eclairage (CIE) y values of 0.077–0.115) is obtained for both isomers due to the improved carrier injection and confinement within the emissive layer. In addition, they showed a significantly better blue‐color purity than analogous molecules based on benzimidazole or phenanthro[9,10‐d]imidazole segments.     

Short Synthetic β‐Sheet Forming Peptide Amphiphiles as Broad Spectrum Antimicrobials with Antibiofilm and Endotoxin Neutralizing Capabilities

Although naturally occurring membrane lytic antimicrobial peptides (AMPs) and their analogs hold enormous promise for antibiotics‐resistant infectious disease therapies, significant challenges such as systemic toxicities, long peptide sequences, poor understanding of structure‐activity relationships, and the potential for compromising innate host defense immunity have greatly limited their clinical applicability. To improve the clinical potential of AMPs, a facile approach is adopted to design a series of short synthetic β‐sheet folding peptide amphiphiles comprised of short recurring (X₁Y₁X₂Y₂)_n‐NH₂ sequences, where X₁ and X₂: hydrophobic residues (Val, Ile, Phe or Trp), Y₁ and Y₂: cationic residues (Arg or Lys), and n: number of repeat units; with systematic variations to the cationic and hydrophobic residues to obtain optimized AMP sequences bearing minimal resemblance to naturally occurring sequences. The designed β‐sheet forming peptides exhibit broad spectrum antimicrobial activities against various clinically relevant microorganisms, including Gram‐positive Staphylococcus epidermidis and Staphylococcus aureus, Gram‐negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida albicans, with excellent selectivities for microbial membranes. Optimal synthetic peptides with n = 2 and n = 3 repeat units, i.e., (IRIK)₂‐NH₂ and (IRVK)₃‐NH₂, efficiently inhibit sessile biofilm bacteria growth leading to biomass reduction. Additionally, sequences with n = 3 repeat units effectively neutralize endotoxins while causing minimal cytotoxicities. Taken together, these findings clearly demonstrate that the rationally designed synthetic β‐sheet folding peptides are highly selective, non‐cytotoxic at antimicrobial levels and have tremendous potential for use as broad spectrum antimicrobial agents to overcome multidrug resistance in a wide range of localized, systemic, or external therapeutic applications.     

Dual‐Salt Mg‐Based Batteries with Conversion Cathodes

Mg batteries as the most typical multivalent batteries are attracting increasing attention because of resource abundance, high volumetric energy density, and smooth plating/stripping of Mg anodes. However, current limitations for the progress of Mg batteries come from the lack of high voltage electrolytes and fast Mg‐insertable structure prototypes. In order to improve their energy or power density, hybrid systems combining Li‐driven cathode reaction with Mg anode process appear to be a potential solution by bypassing the aforementioned limitations. Here, FeS _x (x = 1 or 2) is employed as conversion cathode with 2–4 electron transfers to achieve a maximum energy density close to 400 Wh kg^?1, which is comparable with that of Li‐ion batteries but without serious dendrite growth and polysulphide dissolution. In situ formation of solid electrolyte interfaces on both sulfide and Mg electrodes is likely responsible for long‐life cycling and suppression of S‐species passivation at Mg anodes. Without any decoration on the cathode, electrolyte additive, or anode protection, a reversible capacity of more than 200 mAh g^?1 is still preserved for Mg/FeS₂ after 200 cycles.     

Self‐Assembled Injectable Nanocomposite Hydrogels Stabilized by Bisphosphonate‐Magnesium (Mg2+) Coordination Regulates the Differentiation of Encapsulated Stem Cells via Dual Crosslinking

Nanocomposite hydrogels consist of a polymer matrix embedded with nanoparticles (NPs), which provide the hydrogels with unique bioactivities and mechanical properties. Incorporation of NPs via in situ precipitation in the polymer matrix further enhances these desirable hydrogel properties. However, the noncytocompatible pH, osmolality, and lengthy duration typically required for such in situ precipitation strategies preclude cell encapsulation in the resultant hydrogels. Bisphosphonate (BP) exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as magnesium ions (Mg²⁺). Here, the preparation of nanocomposite hydrogels via self‐assembly driven by bisphosphonate‐Mg²⁺ coordination is described. Upon mixing solutions of polymer bearing BPs, BP monomer (Ac‐BP), and Mg²⁺, this effective and dynamic coordination leads to the rapid self‐assembly of Ac‐BP‐Mg NPs which function as multivalent crosslinkers stabilize the resultant hydrogel structure at physiological pH. The obtained nanocomposite hydrogels are self‐healing and exhibit improved mechanical properties compared to hydrogels prepared by blending prefabricated NPs. Importantly, the hydrogels in this study allow the encapsulation of cells and subsequent injection without compromising the viability of seeded cells. Furthermore, the acrylate groups on the surface of Ac‐BP‐Mg NPs enable facile temporal control over the stiffness and crosslinking density of hydrogels via UV‐induced secondary crosslinking, and it is found that the delayed introduction of this secondary crosslinking enhances cell spreading and osteogenesis.