Killing Of Bacteria Research Articles

A Gram-negative-selective antibiotic that spares the gut microbiome.

Infections caused by Gram-negative pathogens are increasingly prevalent and are typically treated with broad-spectrum antibiotics, resulting in disruption of the gut microbiome and susceptibility to secondary infections1-3. There is a critical need for antibiotics that are selective both for Gram-negative bacteria over Gram-positive bacteria, as well as for pathogenic bacteria over commensal bacteria. Here we report the design and discovery of lolamicin, a Gram-negative-specific antibiotic targeting the lipoprotein transport system. Lolamicin has activity against a panel of more than 130 multidrug-resistant clinical isolates, shows efficacy in multiple mouse models of acute pneumonia and septicaemia infection, and spares the gut microbiome in mice, preventing secondary infection with Clostridioides difficile. The selective killing of pathogenic Gram-negative bacteria by lolamicin is a consequence of low sequence homology for the target in pathogenic bacteria versus commensals; this doubly selective strategy can be a blueprint for the development of other microbiome-sparing antibiotics.

Pt-Ru bimetallic nanoclusters with peroxidase-like activity for antibacterial therapy.

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 μg/mL and 16 μg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.

Long-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

Comparative evaluation of oxygenating agent “blue m gel” and traditional periodontal dressing “Coe-Pak” on patient preference parameters (Pain and wound healing) after surgical depigmentation – A split mouth study

Individuals with high lip line and gummy smile when accompanied withdark colored gingiva have an esthetic concern while smiling. For the management of gingival hyperpigmentation surgical technique with scalpel is still considered the gold standard, although healing may occur by secondary intension and oxygen is one of the essential nutrients for cellular metabolism and production of energy through ATP. It is also involved in collagen synthesis, oxygenative killing of bacteria and angiogenesis. To clinically evaluate and compare the effectiveness of oxygenating agent (Blue M Gel) and traditional periodontal dressing COE-PAK on patient preference parameters (pain and wound healing) after surgical depigmentation. This split-mouth randomized clinical trial was conducted on 5 non-smoking individuals aged 20–40 years irrespective of gender with maxillary or mandibular physiologic gingival pigmentation class (III) and (IV) according to the Dummett–Gupta Oral Pigmentation Index (10 treated sites) who had requested an esthetic treatment for gingival hyperpigmentation of the maxillary or mandibular gingiva. The maxilla or the mandible was randomly divided into two symmetrical parts i.e. from the right second premolar to the midline and from the midline to the left second premolar—to receive either Blue M gel or Coe-Pak as a periodontal dressing after surgical depigmentation with a scalpel. Patient preference parameters such as pain was assessed after 24 hours and 7 days of intervention and re-epithelisation index with toluidine blue was assessed after 1 week and 1 month of intervention. The result of the study demonstrated that pain score and re-epithelisation score was less in Test group (Blue M Gel) as compared to control group (COE-PAK) and was found to be statistically significant. :It can be concluded that Blue M gel can also be a better alternative as a periodontal dressing compared to COE-PAK due to its properties of better healing and decreasing post-operative pain.

Photoactive polymer coatings for antibacterial applications

Because bacteria can readily induce illnesses in the human body, research into new bactericidal approaches remains relevant to the global community. Photoactive materials (e.g., photocatalysts) provide an environmentally-friendly method for killing bacteria with light. By means of light-mediated reactive oxygen generation, photocatalysts are capable of disrupting bacterial membranes. Much research on antibacterial surfaces has focused on planar substrates or physisorbed coatings, which often provide small active surface areas and limited surface-to-volume ratios, and thereby create a need for new design strategies to incorporate photocatalysts onto more scalable supports. To this end, this contribution describes the synthesis of particle-tethered polymer brush coatings, crosslinked with the organic photocatalyst tetrakis(4-carboxyphenyl)porphyrin (TCPP). Successful engineering on SiO2 surfaces was confirmed using X-ray photoelectron spectroscopy, tensiometry, and ellipsometry. Singlet oxygen (1O2) generation was confirmed through dimethyl sulfoxide oxidation experiments under visible (blue) light and bactericidal activity against Escherichia coli was verified through live/dead assays and cell viability tests.

Cetyltrimethylammonium-chloride assisted in situ metabolic incorporation of nano-sized ROS-generating cascade-reaction containers in Gram-positive and Gram-negative peptidoglycan layers for the control of bacterially-induced sepsis

Cascade-reaction containers generating reactive oxygen species (ROS) as an alternative for antibiotic-based strategies for bacterial infection control, require endogenous oxygen-sources and ROS-generation close to or preferably inside target bacteria. Here, this is achieved by cetyltrimethylammonium-chloride (CTAC) assisted in situ metabolic labeling and incorporation of mesoporous SiO2-nanoparticles, dual-loaded with glucose-oxidase and Fe3O4-nanoparticles as cascade-reaction containers, inside bacterial cell walls. First, azide-functionalized d-alanine (D-Ala-N3) was inserted in cell wall peptidoglycan layers of growing Gram-positive pathogens. In Gram-negatives, this could only be achieved after outer lipid-membrane permeabilization, using a low concentration of CTAC. Low concentrations of CTAC had no adverse effect on in vitro blood clotting or hemolysis nor on the health of mice when blood-injected. Next, dibenzocyclooctyne-polyethylene-glycol modified, SiO2-nanoparticles were in situ click-reacted with d-Ala-N3 in bacterial cell wall peptidoglycan layers. Herewith, a two-step cascade-reaction is facilitated inside bacteria, in which glucose-oxidase generates H2O2 at endogenously-available glucose concentrations, while subsequently Fe3O4-nanoparticles catalyze generation of •OH from the H2O2 generated. Generation of •OH inside bacterial cell walls by dual-loaded mesoporous SiO2-nanoparticles yielded more effective in vitro killing of both planktonic Gram-positive and Gram-negative bacteria suspended in 10 % plasma than SiO2-nanoparticles solely loaded with glucose-oxidase. Gram-positive or Gram-negative bacterially induced sepsis in mice could be effectively treated by in situ pre-treatment with tail-vein injected CTAC and d-Ala-N3, followed by injection of dual-loaded cascade-reaction containers without using antibiotics. This makes in situ metabolic incorporation of cascade-reaction containers as described attractive for further investigation with respect to the control of other types of infections comprising planktonic bacteria. Statement of SignificanceIn situ metabolic-incorporation of cascade-reaction-containers loaded with glucose-oxidase and Fe3O4 nanoparticles into bacterial cell-wall peptidoglycan is described, yielding ROS-generation from endogenous glucose, non-antibiotically killing bacteria before ROS inactivates. Hitherto, only Gram-positives could be metabolically-labeled, because Gram-negatives possess two lipid-membranes. The outer membrane impedes direct access to the peptidoglycan. This problem was solved by outer-membrane permeabilization using a quaternary-ammonium compound. Several studies on metabolic-labeling perform crucial labeling steps during bacterial-culturing that in real-life should be part of a treatment. In situ metabolic-incorporation as described, can be applied in well-plates during in vitro experiments or in the body as during in vivo animal experiments. Surprisingly, metabolic-incorporation proceeded unhampered in blood and a murine, bacterially-induced sepsis could be well treated.

Functionalized Mesoporous Polydopamine Nanocarrier with Near-Infrared Laser-Trigged NO Release and Photothermal Effects for the Killing of Pathogenic Bacteria

Functionalized Mesoporous Polydopamine Nanocarrier with Near-Infrared Laser-Trigged NO Release and Photothermal Effects for the Killing of Pathogenic Bacteria

Novel natural osthole-inspired amphiphiles as membrane targeting antibacterials against methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen causing clinical infections and is multi-resistant to many antibiotics, making it urgent need to develop novel antibacterials to combat MRSA. Herein, we designed and prepared a series of novel osthole amphiphiles 6a−6ad by mimicking the structures and function of antimicrobial peptides (AMPs). Antibacterial assays showed that osthole amphiphile 6aa strongly inhibited S. aureus and 10 clinical MRSA isolates with MIC values of 1–2 μg/mL, comparable to that of the commercial antibiotic vancomycin. Additionally, 6aa had the advantages of rapid bacteria killing without readily developing drug resistance, low toxicity, good membrane selectivity, and good plasma stability. Mechanistic studies indicated that 6aa possesses good membrane-targeting ability to bind to phosphatidylglycerol (PG) on the bacterial cell membranes, thereby disrupting the cell membranes and causing an increase in intracellular ROS as well as leakage of proteins and DNA, and accelerating bacterial death. Notably, in vivo activity results revealed that 6aa exhibits strong anti-MRSA efficacy than vancomycin as well as a substantial reduction in MRSA-induced proinflammatory cytokines, including TNF-α and IL-6. Given the impressive in vitro and in vivo anti-MRSA efficacy of 6aa, which makes it a potential candidate against MRSA infections.

Design and evaluation of an MMP-9-responsive hydrogel for vital pulp therapy

ObjectiveTo design and evaluate a matrix metalloproteinase 9 (MMP-9)-responsive hydrogel for vital pulp therapy. MethodsA peptide linker with optimized sensitivity toward MMP-9 was crosslinked with 4-arm poly (ethylene glycol)-norbornene (PEG-NB) by thiol-norbornene photo-polymerization. This resulted in the formation of a hydrogel network in which the peptide IDR-1002 was incorporated. Hydrogel characterization and gelation kinetics were examined with Fourier-transform infrared spectroscopy, scanning electron microscopy, rheological testing, and swelling evaluation. Hydrogel degradation was examined through multiple exposure to pre-activated MMP-9, to simulate flare-ups of dental pulp inflammation. The IDR-1002 released from degraded hydrogels was measured with high-performance liquid chromatography. Effect of IDR-1002 released from hydrogels on one-week-old multispecies oral biofilms was evaluated using confocal laser scanning microscopy. ResultsMMP-9-responsive, injectable, and photo-crosslinkable hydrogels were successfully synthesized. When hydrogel degradation and release of IDR-1002 were examined with exposure to pre-activated MMP-9, IDR-1002 release was significantly correlated with elevated levels of MMP-9 (p < 0.05). The effectiveness of IDR-1002 in killing bacteria in multispecies oral biofilms was significantly enhanced when the hydrogels were immersed in 10 nM or 20 nM pre-activated MMP-9, compared to immersion in phosphate-buffered saline (p < 0.05). ConclusionsThe MMP-9-responsive hydrogel is a promising candidate for on-demand delivery of bioactive agent in vital pulp therapy. Clinical significanceMMP-9 is one of the most important diagnostic and prognostic biomarkers for pulpitis. An MMP-9-responsive hydrogel has potential to be used as an in-situ on-demand release system for the diagnosis and treatment of dental pulp inflammation.

Preparation and characterization of chitosan/polyvinyl alcohol antibacterial sponge materials

This study utilized the freeze-drying method to create a chitosan (CS) and polyvinyl alcohol (PVA) sponge. To enhance its antibacterial properties, curcumin and nano silver (Cur@Ag) were added for synergistic antibacterial. After adding curcumin and nano silver, the mechanical properties of the composite sponge dressing (CS-PVA-Cur@Ag) were improved. The porosity of the composite sponge dressing was closed to 80%, which was helpful for drug release, and it had good water absorption and water retention rate. The nano silver diameter was 50–80 nm, which was optimal for killing bacteria. Antibacterial tests used Escherichia coli and Staphylococcus aureus demonstrated that little nano silver was required to eliminate bacteria. Finally, in the rat full-thickness skin wound model, the composite sponge dressing can promote wound healing in a short time. In summary, CS-PVA-Cur@Ag wound dressing could protect from bacterial infection and accelerate wound healing. Thus, it had high potential application value for wound dressing.

Bosutinib Stimulates Macrophage Survival, Phagocytosis, and Intracellular Killing of Bacteria.

Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection. In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively. In a murine wound infection with vancomycin-resistant Enterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion. Mechanistically, bosutinib stimulates macrophage phagocytosis of bacteria by upregulating surface expression of bacterial uptake markers Dectin-1 and CD14 and promoting actin remodeling. Bosutinib also stimulates bacterial killing by elevating the intracellular levels of reactive oxygen species. Moreover, bosutinib drives NF-κB activation, which protects infected macrophages from dying. Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.

Wearable Light Sources for Antimicrobial Photodynamic Therapy

SignificanceOrganic light emitting diodes (OLEDs) are desirable light sources for ambulatory photodynamic therapy (PDT) due to their compact size, light weight, and the possibility to be fabricated on a flexible substrate. Herein, we demonstrate the effectiveness of using red OLEDs as light sources for killing Staphylococcus aureus. ApproachFirstly, large area flexible OLEDs were fabricated. Then the efficacy of OLEDs for killing bacteria was tested on 96-well plates using different concentrations of methylene blue as a photosensitizer. Samples were illuminated for 1, 3 and 6 hours at an irradiance of 6 mW/cm2. The growth of live bacteria was monitored using a microplate reader. ResultsOur results showed that OLED-PDT can kill more than 99% of bacteria which provides effective antimicrobial treatment. ConclusionsThis work shows the great potential of OLEDs as new wearable light sources for antimicrobial treatment of Staphylococcus aureus.

Bacterial membrane-induced disassembly of fluorescein aggregates enables selective imaging and killing of Gram-positive bacteria

The escalating health threats posed by bacteria and the pressing issue of antibiotic resistance underscore the urgent need for selective detection technologies and antimicrobial reagents. Fluorescein's biocompatibility renders it the preferred fluorescent dye for in vivo imaging. This study reveals that compounds from the aliphatic chain-derived fluorescein series (BMP-alkyl) not only selectively stain and fluorescently image Gram-positive bacteria but also demonstrate the ability to rapidly eliminate them. The discovery of fluorescein's antibacterial properties is poised to have applications in antibiotic research due to its excellent biocompatibility. These amphiphilic BMP-alkyl compounds were easily synthesized through a one-step amidation process involving dicarboxyfluorescein and long-chain fatty amines. In aqueous solutions, the formed aggregates exhibited complete fluorescence quenching. Upon encountering the Gram-positive bacterial membrane, BMP-alkyl compounds underwent depolymerization, resulting in a single fluorescent molecule and the activation of fluorescence. Subsequently, as these amphiphilic fluoresceins continuously combined and entered the bacterial interior, the potential for bacterial membrane depolarization, membrane structure damage, and ultimately bacterial death ensued.

Compartmentalization into Outer and Inner Shells of Hollow Nanospheres for Antibiosis Based on Chemistry and Physical Damages.

There is a substantially ascending demand for nonantibiotic strategies to overcome the resistance of bacterial infections. Here, the discovery of a distinctive antibacterial structure is reported. The novel structure of nanoparticle strategy is proposed for appreciable bacteria killing by the smart design of the delayed addition of crosslinkers into the reaction mixture. [2-(methacryloyloxy)ethyl]trimethylammonium chloride solution (MTCl), a water-soluble ionic liquid (IL), has narrow-size material distribution, good whiteness, and high weather resistance. The quaternary ammonium salt is utilized to efficiently permeate cell membranes through electrostatic interaction, accordingly, boasting a beneficiary of antibacterial properties. More importantly, it allows bacteria to attach the nanomaterials easily, especially the double-shelled nanosphere. In light of the introduction of 9-amino(9-deoxy)ep-quinine (QNNH2) on its inner shell, it blocks the nucleic acid and glucose metabolism in bacteria, which is betterment of the antibacterial activity of double-shelled structure nanoparticle compared to other structure of nanomaterials. This physical/chemical/biological triple antibacterial process eliminates the need for traditional antibiotics, and the fabrication strategies and material properties described here provide insights into the design of antibacterial nanomaterials based on chemical and physical effects.

Quasi-MOF-Engineered MnOx/CeBTC Multinanozyme as a Robust Self-Cascade ROS Generator toward Antibacterial Face Mask.

It is of great importance to endow personal protective equipments with bactericidal property combating against infected pathogens. Nanozyme that can generate reactive oxygen species (ROS) in an enzyme-catalytic manner is regarded as a novel and promising nanobactericide. But until now, very rare of them is designed specifically for personal protective equipments. In this study, a multinanozyme of manganese oxide supported on Ce-containing MOF (CeBTC) is constructed with post-engineering via a quasi-metal-organic framework (MOF) strategy (denoted as MnOx/q-CeBTC). The strategy enables a full exposure of the metal cluster nodes, introduction of new active Mn─O─Ce bonds and strengthens interaction between the metal nodes and the guest oxide. As an advanced multinanozyme, the MnOx/q-CeBTC exhibits excellent multiple enzymatic activities at low temperature, and enables abundant and self-cascade ROS generation without H2O2 addition. This empowers it with high efficiency in bacteria killing, which is also reflected when incorporated into face mask to combat against pathogen invasion even at low temperature. The results achieved in this work provide guidance for rational design of effective bactericide based on nanozyme and broaden their application in personal protective equipment and other fields.

Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.

Cas9-assisted biological containment of a genetically engineered human commensal bacterium and genetic elements

Sophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Engineered biosensing bacteria outfitted with such circuits can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiring thyA via horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacterium Bacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.

Near-infrared light triggered upconversion nanocomposites with multifunction of enhanced antimicrobial photodynamic therapy and gas therapy for inflammation regulation

Antibacterial photodynamic therapy (aPDT) is highly effective in killing bacteria, while the problem of hypoxia and limited light penetration in deep tissue has not been properly solved. In addition, few aPDT works take into account the regulation of inflammation, which is an important regulatory process after antimicrobial therapy and the final purpose of treatment. In this work, to address the above isssues, we have designed a multi-functional composite UCNPs-Ce6-Mn(CO)5Br@Silane (referred to as UCM@Si), which consists of several key components: Up-conversion nanoparticles (UCNPs: NaErF4:Tm3+@NaYF4:Yb3+), Chlorin e6 (Ce6) and Manganese pentacarbonyl bromide (Mn(CO)5Br). When exposed to near-infrared (NIR) light (980 nm), the UCNPs can emit strong red light at 655 nm which further trigger the aPDT of Ce6. The generated reactive oxygen (ROS) subsequently break the metal carbonyl bond of Mn(CO)5Br, leading to the production of carbon monoxide (CO) molecules as well as manganese ions (Mn2+), which further decomposes hydrogen peroxide (H2O2) in the microenvironment to oxygen (O2). Therefore, this simple nanocomposite not only provides substantial self-oxygen replenishment for enhanced aPDT, but also facilitates effective inflammation regulation via CO across a wide range of deep infections. This approach leverages the unique properties of these materials to combat bacterial infections by simultaneously killing bacteria, regulating inflammation, and enhancing the oxygen levels in the affected microenvironment. This O2 and CO gas based aPDT treatment system offers a promising approach to comprehensively address microbial-induced infectious diseases, particularly deep infections, holding the potential clinical applications.

FcLR-Chitosan/Pullulan nanofibers: Boosted antibacterial activity and decreased cytotoxicity

Natural and environmentally benign electrospun polymeric nanofibers (NFs) with distinctive features, unique physiochemical and biological properties, and high susceptibility to carry non-toxic antibacterial cargoes, e.g., ferrocenyl-based compounds, have emerged as a neo-tool for killing bacteria. Here, the antibacterial FcLR-Chit/Pull NFs were fabricated through three steps: 1) synthesis of FcLR-Chit via the attachment of chitosan to Ferrocenyl Lawesson’s Reagent (FcLR), 2) blending of the FcLR-Chit at various concentrations with the natural polymer of pullulan, and 3) electrospinning. The successfully characterized FcLR-Chit/Pull NFs with a homogenous distribution of FcLR-Chit inside the pullulan matrix were thermally stable up to 270–290 ºC and mechanically stable with an increased elongation at break (EAB) (30.0–42.2%) and decreased tensile strength (TS) (1.1–2.3 MPa) compared to the pure pullulan NFs with the EAB of 19.0% and TS of 3.6 MPa. Pure pullulan NFs and FcLR-Chit/Pull NFs (0.1 wt%, 1.0 wt%, and 5.0 wt%) showed insignificant cytotoxicity on the fibroblast cell lines (L929). The antibacterial activity was detected in the trend of FcLR-Chit/Pull NFs (5.0 wt%)>FcLR-Chit powder (5.0 wt% in water)>FcLR-Chit/Pull NFs (1.0 wt%)>FcLR powder (5.0 wt% in water)>FcLR-Chit/Pull NFs (0.1 wt%)>chitosan powder (5.0 wt% in water)> pure pullulan NFs. The FcLR-Chit/Pull NFs (5.0 wt%) with an average diameter of 365 nm, insignificant cytotoxicity on L929 cells within 24 h and 48 h, and boosted antibacterial activity with the inhibition zone diameter of 1.95 mm against Gram-negative E. Coli and 1.76 mm against Gram-positive S. aureus bacteria were chosen as the optimal nanofibrous candidate for the future bactericidal applications.

Leaf‐Mimicking Superstructured Porous Membrane with Multiple Bioactive Pro‐Healing Functions for Effective Guided Bone Regeneration

AbstractBarrier membrane, a key material for guided bone regeneration surgery, is applied between soft and hard tissue interfaces in complex oral environment. The abilities to integrate contradictory requirements and self‐regulate the local microenvironment are highly desirable for barrier membrane but remain challenging to achieve. Herein, inspired by the leaf's hierarchical multifunctional synergy, a kind of superstructured porous membrane (SPM), integrating asymmetric surface pores, interconnected macropores and functional micropores, is developed based on the combination of breath figure and phase separation. For the SPM, the densely porous layer can inhibit penetration of soft tissue cells and maintain osteogenic space, and the loosely porous layer with interconnected microporous channels can effectively promote the adhesion and proliferation of osteoblasts, help to transport nutrients, and expose functional components. Meanwhile, porous carbon nanospheres introduced into SPM as multifunctional core components can ameliorate the undesirable microenvironment by scavenging reactive oxygen species, repairing bioelectrical environment, and killing bacteria, thus achieving multiple bioactive pro‐healing functions for efficient bone regeneration in vivo. These findings can open an appealing avenue for developing high‐performance barrier membranes as well as many other implant materials.