Bacteriophage Can Prevent Encrustation and Blockage of Urinary Catheters by Proteus mirabilis.

Proteus mirabilis forms dense crystalline biofilms on catheter surfaces that occlude urine flow, leading to serious clinical complications in long-term catheterized patients, but there are presently no truly effective approaches to control catheter blockage by this organism. This study evaluated the potential for bacteriophage therapy to control P. mirabilis infection and prevent catheter blockage. Representative in vitro models of the catheterized urinary tract, simulating a complete closed drainage system as used in clinical practice, were employed to evaluate the performance of phage therapy in preventing blockage. Models mimicking either an established infection or early colonization of the catheterized urinary tract were treated with a single dose of a 3-phage cocktail, and the impact on time taken for catheters to block, as well as levels of crystalline biofilm formation, was measured. In models of established infection, phage treatment significantly increased time taken for catheters to block (∼ 3-fold) compared to untreated controls. However, in models simulating early-stage infection, phage treatment eradicated P. mirabilis and prevented blockage entirely. Analysis of catheters from models of established infection 10 h after phage application demonstrated that phage significantly reduced crystalline biofilm formation but did not significantly reduce the level of planktonic cells in the residual bladder urine. Taken together, these results show that bacteriophage constitute a promising strategy for the prevention of catheter blockage but that methods to deliver phage in sufficient numbers and within a key therapeutic window (early infection) will also be important to the successful application of phage to this problem.

Nanoprecipitation of polymeric nanoparticle micelles based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), for intracellular delivery applications.

Biodistribution of nanoparticle-based intracellular delivery systems is mediated primarily by particle size and physicochemical properties. As such, overcoming the rapid removal of these by the reticuloendothelial system remains a significant challenge. To date, a number of copolymer nanoparticle systems based on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl methacrylate (DPA), displaying biomimetic and pH responsive properties, have been published, however these have been predominately polymersome based, whilst micelle systems have remained relatively unexplored. This study utilised nanoprecipitation to investigate the effects of solvent and buffer choice upon micelle size and polydispersity, and found using methanol produced monodisperse micelles of circa 70 nm diameter, whilst ethanol produced polydisperse systems with nanoparticles of circa 128 nm diameter. The choice of aqueous buffer, dialysis of the systems, extended storage, and exposure to a wide temperature range (5-70 °C) had no significant effect on micelle size, and the systems were highly resistant to dilution, indicating excellent colloidal stability. Optimisation of the nanoprecipitation process, post precipitation, was investigated, and model drugs successfully loaded whilst maintaining system stability. Subsequent in vitro studies suggested that the micelles were of negligible cellular toxicity, and an apparent cellular uptake was observed via confocal laser scanning microscopy. This paper presents the first report of an optimised nanoprecipitation methodology for the formation of MPC-DPA nanoparticle micelles, and in doing so achieved monodisperse systems with the size and physicochemical characteristics seen as desirable for long circulating therapeutic delivery vehicles.

Pristine Ti3C2Tx MXene Enables Flexible and Transparent Electrochemical Sensors.

In the era of the internet of things, there exists a pressing need for technologies that meet the stringent demands of wearable, self-powered, and seamlessly integrated devices. Current approaches to developing MXene-based electrochemical sensors involve either rigid or opaque components, limiting their use in niche applications. This study investigates the potential of pristine Ti3C2Tx electrodes for flexible and transparent electrochemical sensing, achieved through an exploration of how material characteristics (flake size, flake orientation, film geometry, and uniformity) impact the electrochemical activity of the outer sphere redox probe ruthenium hexamine using cyclic voltammetry. The optimized electrode made of stacked large Ti3C2Tx flakes demonstrated excellent reproducibility and resistance to bending conditions, suggesting their use for reliable, robust, and flexible sensors. Reducing electrode thickness resulted in an amplified faradaic-to-capacitance signal, which is advantageous for this application. This led to the deposition of transparent thin Ti3C2Tx films, which maintained their best performance up to 73% transparency. These findings underscore its promise for high-performance, tailored sensors, marking a significant stride in advancing MXene utilization in next-generation electrochemical sensing technologies. The results encourage the analytical electrochemistry field to take advantage of the unique properties that pristine Ti3C2Tx electrodes can provide in sensing through more parametric studies.

Mid-Infrared Electrochromics Enabled by Intraband Modulation in Carbon Nanotube Networks.

Tuneable infrared properties, such as transparency and emissivity, are highly desirable for a range of applications, including thermal windows and emissive cooling. Here, we demonstrate the use of carbon nanotube networks spray-deposited onto an ionic liquid-infused membrane to fabricate devices with electrochromic modulation in the mid-infrared spectrum, facilitating control of emissivity and apparent temperature. Such modulation is enabled by intraband transitions in unsorted single-walled carbon nanotube networks, allowing the use of scalable nanotube inks for printed devices. These devices are optimized by varying film thickness and sheet resistance, demonstrating the emissivity modulation (from ∼0.5 to ∼0.2). These devices and the understanding thereof open the door to selection criteria for infrared electrochromic materials based on the relationship between band structure, electrochemistry, and optothermal properties to enable the development of solution-processable large-area coatings for widespread thermal management applications.

Exotic Electronic Properties of 2D Nanosheets Isolated from Liquid Phase Exfoliated Phyllosilicate Minerals.

Spectrally inactive, electrically insulating, and chemically inert are adjectives broadly used to describe phyllosilicate minerals like mica and chlorite. Here, the above is disproved by demonstrating aqueous suspensions of liquid exfoliated nanosheets from five bulk mica types and chlorite schist. Nanosheet quality is confirmed via transmission electron and X-ray photoelectron spectroscopies, as well as electron diffraction. Through Raman spectroscopy, a previously unreported size- and layer-dependent spectral fingerprint is observed. When analyzing the high-yield suspensions (≈1 mg mL-1 ) through UV-vis spectroscopy, all phyllosilicates present bandgap (Eg ) narrowing from ≈7 eV in the bulk to ≈4 eV for monolayers. Unusually, the bandgap is inversely proportional to the areal size (A) of the nanosheets, measured via atomic force microscopy. Due to an unrecorded quantum confinement effect, nanosheet electronic properties scale toward semiconducting behavior (bandgap ≈3 eV) as nanosheet area increases. Furthermore, modeling X-ray diffraction spectra shows that the root cause of the initial bandgap narrowing is lattice relaxation. Finally, with their broad range of isomorphically substituted ions, phyllosilicate nanosheets show remarkable catalytic properties for hydrogen production.

Tuneable synthetic reduced graphene oxide scaffolds elicit high levels of three-dimensional glioblastoma interconnectivity in vitro.

Three-dimensional tissue scaffolds have utilised nanomaterials to great effect over the last decade. In particular, scaffold design has evolved to consider mechanical structure, morphology, chemistry, electrical properties, and of course biocompatibility - all vital to the performance of the scaffold and how successful they are in developing cell cultures. We have developed an entirely synthetic and tuneable three-dimensional scaffold of reduced graphene oxide (rGO) that shows good biocompatibility, and favourable mechanical properties as well as reasonable electrical conductivity. Importantly, the synthesis is scaleable and suitable for producing scaffolds of any desired geometry and size, and we observe a high level of biocompatibility and cell proliferation for multiple cell lines. In particular, one of the most devastating forms of malignant brain cancer, glioblastoma (GBM), grows especially well on our rGO scaffold in vitro, and without the addition of response-specific growth factors. We have observed that our scaffold elicits spontaneous formation of a high degree of intercellular connections across the GBM culture. This phenomenon is not well documented in vitro and nothing similar has been observed in synthetic scaffolds without the use of response-specific growth factors - which risk obscuring any potential phenotypic behaviour of the cells. The use of scaffolds like ours, which are not subject to the limitations of existing two-dimensional substrate technologies, provide an excellent system for further investigation into the mechanisms behind the rapid proliferation and success of cancers like GBM. These synthetic scaffolds can advance our understanding of these malignancies in the pursuit of improved theranostics against them.

Size selection and thin-film assembly of MoS2 elucidates thousandfold conductivity enhancement in few-layer nanosheet networks.

Printed electronics based on liquid-exfoliated nanosheet networks are limited by inter-nanosheet junctions and thick films which hinder field-effect gating. Here, few-layer molybdenum disulfide nanosheets are assembled by Langmuir deposition into thin films, and size selection is shown to lead to a thousandfold conductivity enhancement with potential applicability to all nanosheet networks.

Nanosheet-Stabilized Emulsions: Near-Minimum Loading and Surface Energy Design of Conductive Networks.

Here, we develop a framework for assembly, understanding, and application of functional emulsions stabilized by few-layer pristine two-dimensional (2D) nanosheets. Liquid-exfoliated graphene and MoS2 are demonstrated to stabilize emulsions at ultralow nanosheet volume fractions, approaching the minimum loading achievable with 2D materials. These nanosheet-stabilized emulsions allow controlled droplet deposition free from the coffee ring effect to facilitate single-droplet devices from minute quantities of material or assembly into large-area films with high network conductivity. To broaden the range of compositions and subsequent applications, an understanding of emulsion stability and orientation in terms of surface energy of the three phases is developed. Importantly, this model facilitates determination of the surface energies of the nanosheets themselves and identifies strategies based on surface tension and pH to allow design of emulsion structures. Finally, this approach is used to prepare conductive silicone emulsion composites with a record-low loading level and excellent electromechanical sensitivity. The versatility of these nanosheet-stabilized emulsions illustrates their potential for low-loading composites, thin-film formation and surface energy determination, and the design of functional structures for a range of segregated network applications.

Explosive percolation yields highly-conductive polymer nanocomposites.

Explosive percolation is an experimentally-elusive phenomenon where network connectivity coincides with onset of an additional modification of the system; materials with correlated localisation of percolating particles and emergent conductive paths can realise sharp transitions and high conductivities characteristic of the explosively-grown network. Nanocomposites present a structurally- and chemically-varied playground to realise explosive percolation in practically-applicable systems but this is yet to be exploited by design. Herein, we demonstrate composites of graphene oxide and synthetic polymer latex which form segregated networks, leading to low percolation threshold and localisation of conductive pathways. In situ reduction of the graphene oxide at temperatures of <150 °C drives chemical modification of the polymer matrix to produce species with phenolic groups, which are known crosslinking agents. This leads to conductivities exceeding those of dense-packed networks of reduced graphene oxide, illustrating the potential of explosive percolation by design to realise low-loading composites with dramatically-enhanced electrical transport properties.

Role of release modifiers to modulate drug release from fused deposition modelling (FDM) 3D printed tablets.

Although hot melt extrusion (HME) has been used in combination with fused deposition modelling (FDM) three-dimensional printing (3DP), suitable feedstock materials such as polymeric filaments with optimum properties are still limited. In this study, various release modifying excipients, namely, poly(vinyl alcohol) (PVA), Soluplus®, polyethylene glycol (PEG) 6000, Eudragit® RL PO/RS PO, hydroxypropyl methylcellulose (HPMC) K4M/E10M/K100M, Kollidon® vinyl acetate 64 (VA 64)/17PF/30, were used as a release modulating tool to control the drug release from 3D printed sustained release tablets. Ibuprofen (as the model drug) and ethyl cellulose (as the polymeric matrix), along with various release modifiers, were blended and extruded into filaments through a twin-screw extruder. Then these filaments were printed into cylindrical tablets through FDM 3DP technique and their surface morphology, thermal stability, solid-state, mechanical properties, dose accuracy and drug release behaviors were investigated. The solid-state analysis of 3D printed tablets exhibited the amorphous nature of the drug dispersed in the polymer matrices. Although all these prepared filaments could be successfully printed without failing during the FDM 3DP process, the mechanical characterization showed that the filament stiffness and brittleness could be adjusted significantly by changing the type of release modifiers. Moreover, in vitro drug release studies revealed that the drug release could simply be controlled over 24 h by only changing the type of release modifiers. All ibuprofen (IBP) loaded 3D printed tablets with ethyl cellulose (EC) matrix, especially with PEG as the release modifier, showed great potential in releasing IBP in a zero-order reaction. In conclusion, all the results illustrated that the HME/FDM approach and optimized formulation compositions can be an attractive option for the development of pharmaceutical tablets and implants where adjustable drug release patterns are necessary.

Magnetic Field Triggerable Macroporous PDMS Sponge Loaded with an Anticancer Drug, 5-Fluorouracil.

This study aims to prepare, optimize, and characterize magnetic-field-sensitive sugar-templated polydimethylsiloxane (PDMS) sponges for localized delivery of an anticancer drug, 5-fluorouracil (FLU). For this purpose, different concentrations of carbonyl iron (CI) and magnetite Fe3O4 nanopowders were embedded as magnetosensitive materials in PDMS resins for the fabrication of macroporous sponges via a sugar-template process. The process is environmentally friendly and simple. The fabricated interconnected macroporous magnetic particles loaded PDMS sponges possess flexible skeletons and good recyclability because of their recoverability after compression (deformation) without any breakdown. The prepared magnetic PDMS sponges were evaluated for their morphology (SEM and EDS), porosity (absorbency), elastic modulus, deformation under a magnetic field, thermostability, and in vitro cell studies. All physicochemical and magnetomechanical analysis confirmed that the optimized magnetic-field-sensitive PDMS sponge can provide an efficient method for delivering an on-demand dose of anticancer drug solutions at a specific location and timing with the aid of controlled magnetic fields.

Bone regeneration potential of a soybean-based filler: experimental study in a rabbit cancellous bone defects.

Autologous and allogenic bone grafts are considered as materials of choice for bone reconstructive surgery, but limited availability, risks of transmittable diseases and inconsistent clinical performances have prompted the development of alternative biomaterials. The present work compares the bone regeneration potential of a soybean based bone filler (SB bone filler) in comparison to a commercial 50:50 poly(D: ,L: lactide-glycolide)-based bone graft (Fisiograft((R)) gel) when implanted into a critical size defect (6-mm diameter, 10-mm length) in rabbit distal femurs. The histomorphometric and microhardness analyses of femoral condyles 4, 8, 16 and 24 weeks after surgery showed that no significant difference was found in the percentage of both bone repair and bone in-growth in the external, medium and inner defect areas. The SB filler-treated defects showed significantly higher outer bone formation and microhardness results at 24 weeks than Fisiograft((R)) gel (P < 0.05). Soybean-based biomaterials clearly promoted bone repair through a mechanism of action that is likely to involve both the scaffolding role of the biomaterial for osteoblasts and the induction of their differentiation.

Investigation of water vapour sorption mechanism of starch-based pharmaceutical excipients.

Starch-based excipients are commonly used in oral solid dosage forms. The effect of particle size and pregelatinisation level of starch-based excipients on their water absorption behaviour have been evaluated. The results showed that starch-based excipients have type ii isotherms, indicating that the principal mechanism of sorption is the formation of monolayer coverage and multilayer water molecules (10-80 RH %). It was found that the particle size of starch-based excipients did not have any influence on the rate of water sorption, whereas the level of pregelatinisation changed the kinetics of water sorption-desorption. Results showed that the higher the degree of pregelatinisation, the higher the rate of water absorption, which is irrespective of particle size. SEM images showed that a partially gelatinised starch had a firm granular structure with small pores and channels on the surface while a fully gelatinised starch had more irregular and spongy like surface with a degree of fractured particles.

A Novel Inducible Prophage from Burkholderia Vietnamiensis G4 is Widely Distributed across the Species and Has Lytic Activity against Pathogenic Burkholderia.

Burkholderia species have environmental, industrial and medical significance, and are important opportunistic pathogens in individuals with cystic fibrosis (CF). Using a combination of existing and newly determined genome sequences, this study investigated prophage carriage across the species B. vietnamiensis, and also isolated spontaneously inducible prophages from a reference strain, G4. Eighty-one B. vietnamiensis genomes were bioinformatically screened for prophages using PHASTER (Phage Search Tool Enhanced Release) and prophage regions were found to comprise up to 3.4% of total genetic material. Overall, 115 intact prophages were identified and there was evidence of polylysogeny in 32 strains. A novel, inducible Mu-like phage (vB_BvM-G4P1) was isolated from B. vietnamiensis G4 that had lytic activity against strains of five Burkholderia species prevalent in CF infections, including the Boston epidemic B. dolosa strain SLC6. The cognate prophage to vB_BvM-G4P1 was identified in the lysogen genome and was almost identical (>93.5% tblastx identity) to prophages found in 13 other B. vietnamiensis strains (17% of the strain collection). Phylogenomic analysis determined that the G4P1-like prophages were widely distributed across the population structure of B. vietnamiensis. This study highlights how genomic characterization of Burkholderia prophages can lead to the discovery of novel bacteriophages with potential therapeutic or biotechnological applications.

Surfactant-free liquid-exfoliated copper hydroxide nanocuboids for non-enzymatic electrochemical glucose detection.

To facilitate printable sensing solutions particles need to be suspended and stabilised in a liquid medium. Hansen parameters were used to identify that alcohol-water blends are ideal for stabilising colloidal copper hydroxide in dispersion. The suspended material can be further separated in various size fractions with a distinct cuboid geometry which was verified using atomic force microscopy. This facilitates the development of Raman spectroscopic metrics for determining particle sizes. This aspect ratio is related to the anisotropic crystal structure of the bulk crystallites. As the size of the nanocuboids decreases electrochemical sensitivity of the material increases due to an increase in specific surface area. Electrochemical glucose sensitivity was investigated using both cyclic voltammetry and chronoamperometry. The sensitivity is noted to saturate with film thickness. The electrochemical response of 253 mA M-1 cm-2 up to 0.1 mM and 120 mA cm-2 up to 0.6 mM allow for calibration of potential devices. These results indicate suitability for use as a glucose sensor and, due to the surfactant-free, low boiling point solvent approach used to exfoliate the nanocuboids, it is an ideal candidate for printable solutions. The ease of processing will also allow this material to be integrated in composite films for improved functionality in future devices.

Laser-Deposited Carbon Aerogel Derived from Graphene Oxide Enables NO2-Selective Parts-per-Billion Sensing.

Laser-deposited carbon aerogel is a low-density porous network of carbon clusters synthesized using a laser process. A one-step synthesis, involving deposition and annealing, results in the formation of a thin porous conductive film which can be applied as a chemiresistor. This material is sensitive to NO2 compared to ammonia and other volatile organic compounds and is able to detect ultra-low concentrations down to at least 10 parts-per-billion. The sensing mechanism, based on the solubility of NO2 in the water layer adsorbed on the aerogel, increases the usability of the sensor in practically relevant ambient environments. A heating step, achieved in tandem with a microheater, allows the recovery to the baseline, making it operable in real world environments. This, in combination with its low cost and scalable production, makes it promising for Internet-of-Things air quality monitoring.

Edge profile of commercially available square-edged intraocular lenses: Part 2.

PURPOSE: To analyze the sharpness of the posterior optic edge and edge thickness of intraocular lenses (IOLs) marketed with a square-edged profile. SETTING: University of Brighton and Brighton and Sussex University Hospitals NHS Trust, Brighton, England. DESIGN: Laboratory study. METHODS: Fourteen square-edged 20.0 diopter IOLs were analyzed, including 9 hydrophobic IOLs (AF-1, AF-1 iSert, Clareon, EyeCee One Crystal, CT Lucia, Envista, EyeCee One, Vivinex iSert, and RayOne Hydrophobic) and 5 hydrophilic IOLs (Asphira, CT Asphina, Incise, Synthesis, and RayOne Hydrophilic). All the IOLs were scanned following a previously published standardized technique using environmental scanning electron microscopy. The posterior optic edges were scanned at a magnification of ×500 and ×200 to measure the radius of curvature of the posterior optic edges and the optic edge thickness. RESULTS: The radius of curvature of the posterior optic edges ranged from 4.6 to 20.6 µm. Except for the Incise IOL (7.7 µm), all hydrophilic IOLs (Synthesis [10.6 µm], Asphira [13.7 µm], RayOne Hydrophilic [14.0 µm], CT Asphina [13.7 µm]) had a radius of curvature greater than 10.0 µm. For the hydrophobic IOLs, the radius of curvature was less than 10.0 µm for the Clareon (7.9 µm), EyeCee One Crystal (4.7 µm), Vivinex iSert (7.6 µm), and CT Lucia (4.6 µm), and greater than 10.0 µm for the Envista (19.7 µm), EyeCee One (13.7 µm), AF-1 iSert (19.7 µm), AF-1 (19.7 µm) and the RayOne Hydrophobic (20.6 µm). The Vivinex iSert (150.5 µm) and the Incise (218.2 µm) were the thinnest IOLs, and the RayOne Hydrophobic (375.8 µm) and RayOne Hydrophilic IOLs (477.1 µm) were the thickest of the hydrophobic and hydrophilic IOLs, respectively. CONCLUSIONS: Commercially marketed square-edged IOLs still differed in the sharpness of the posterior optic edge. More hydrophobic IOLs have rounder edges than those studied 10 years ago. Variations in the edge profile of hydrophobic IOLs were greater compared with the hydrophilic IOLs.

Charge Transfer Hybrids of Graphene Oxide and the Intrinsically Microporous Polymer PIM-1.

Nanohybrid materials based on nanoparticles of the intrinsically microporous polymer PIM-1 and graphene oxide (GO) are prepared from aqueous dispersions with a reprecipitation method, resulting in the surface of the GO sheets being decorated with nanoparticles of PIM-1. The significant blueshift in fluorescence signals for the GO/PIM-1 nanohybrids indicates modification of the optoelectronic properties of the PIM-1 in the presence of the GO due to their strong interactions. The stiffening in the Raman G peak of GO (by nearly 6 cm-1) further indicates p-doping of the GO in the presence of PIM. Kelvin probe force microscopy (KPFM) and electrochemical reduction measurements of the nanohybrids provide direct evidence for charge transfer between the PIM-1 nanoparticles and the GO nanosheets. These observations will be of importance for future applications of GO-PIM-1 nanohybrids as substrates and promoters in catalysis and sensing.