New 2D Metal-Organic Monoacid Framework (MOmAF): Realization of Extreme Water Repellence.

Metal-organic frameworks (MOFs) are normally moisture-sensitive and unstable in aqueous environments, which has considerably limited their practical applications because water/moisture is ubiquitous in many industrial processes. New materials with superior water stability are, therefore, in great demand and vital to their practical applications. Here, a novel oil/water interfacial assembly strategy is demonstrated for the synthesis of a new class of metal-organic monoacid framework (MOmAF) with exceptional water stability and chemical stability. Superhydrophobic 2D sheets are synthesized at room temperature, while 1D nanotubes are obtained via the self-scrolling of their 2D sheets for the first time. In addition, a simple sequential drop-casting method is developed to coat as-synthesized MOmAF structures onto porous membranes. This can potentially open up new avenues in the design of superhydrophobic self-cleaning MOmAF materials without tedious post-synthetic modifications and usher in a new class of materials meeting industrial needs.

Green and Integrated Wearable Electrochemical Sensor for Chloride Detection in Sweat.

Wearable sensors for sweat biomarkers can provide facile analyte capability and monitoring for several diseases. In this work, a green wearable sensor for sweat absorption and chloride sensing is presented. In order to produce a sustainable device, polylactic acid (PLA) was used for both the substrate and the sweat absorption pad fabrication. The sensor material for chloride detection consisted of silver-based reference, working, and counter electrodes obtained from upcycled compact discs. The PLA substrates were prepared by thermal bonding of PLA sheets obtained via a flat die extruder, prototyped in single functional layers via CO2 laser cutting, and bonded via hot-press. The effect of cold plasma treatment on the transparency and bonding strength of PLA sheets was investigated. The PLA membrane, to act as a sweat absorption pad, was directly deposited onto the membrane holder layer by means of an electrolyte-assisted electrospinning technique. The membrane adhesion capacity was investigated by indentation tests in both dry and wet modes. The integrated device made of PLA and silver-based electrodes was used to quantify chloride ions. The calibration tests revealed that the proposed sensor platform could quantify chloride ions in a sensitive and reproducible way. The chloride ions were also quantified in a real sweat sample collected from a healthy volunteer. Therefore, we demonstrated the feasibility of a green and integrated sweat sensor that can be applied directly on human skin to quantify chloride ions.

A SERS-Active Electrospun Polymer Mesh for Spatially Localized pH Measurements of the Cellular Microenvironment.

Extracellular pH (pHe) is an important chemical factor in many cellular processes and disease pathologies. The routine sampling of pHe in vitro could lead to innovative advances in therapeutics. To this end, we have fabricated a novel gold-coated polymer mesh, which facilitates the real-time measurement of pHe via surface-enhanced Raman scattering (SERS). In this proof of concept study, we apply our SERS sensor to measure metabolically induced changes in the pHe of carcinoma-derived cell line HepG2/C3A. We demonstrate that gold-coated polyurethane electrospun nanofibers (AuNF) have strong and reproducible SERS spectra of surface-adsorbed analytes. By functionalizing AuNF with pH-responsive reporter 4-mercaptobenzoic acid (MBA), we have developed an accurate pH SERS sensor for the extracellular microenvironment. We cultured HepG2/C3A on the surface of MBA-AuNF and measured an acidic shift in pHe at the cell-fiber interface. Following exposure to staurosporine, an apoptosis-inducing drug, we observed changes in the HepG2/C3A cellular morphology indicative of controlled cell death, and detected an increase in the pHe of HepG2/C3A. These results demonstrate how subtle changes in pHe, induced by the metabolic activity of cells, can be measured with our novel SERS sensor MBA-AuNF. The excellent pH measurement performance of MBA-AuNF provides a unique platform to study extracellular pH on the microscale and will help to deepen our understanding of pHe in disease pathology.

Nylon-6/chitosan core/shell antimicrobial nanofibers for the prevention of mesh-associated surgical site infection.

The state-of-the-art hernia meshes, used in hospitals for hernia repair, are predominantly polymeric textile-based constructs that present high mechanical strength, but lack antimicrobial properties. Consequently, preventing bacterial colonization of implanted prosthetic meshes is of major clinical relevance for patients undergoing hernia repair. In this study, the co-axial electrospinning technique was investigated for the development of a novel mechanically stable structure incorporating dual drug release antimicrobial action. Core/shell structured nanofibers were developed, consisting of Nylon-6 in the core, to provide the appropriate mechanical stability, and Chitosan/Polyethylene oxide in the shell to provide bacteriostatic action. The core/shell structure consisted of a binary antimicrobial system incorporating 5-chloro-8-quinolinol in the chitosan shell, with the sustained release of Poly(hexanide) from the Nylon-6 core of the fibers. Homogeneous nanofibers with a "beads-in-fiber" architecture were observed by TEM, and validated by FTIR and XPS. The composite nanofibrous meshes significantly advance the stress-strain responses in comparison to the counterpart single-polymer electrospun meshes. The antimicrobial effectiveness was evaluated in vitro against two of the most commonly occurring pathogenic bacteria; S. aureus and P. aeruginosa, in surgical site infections. This study illustrates how the tailoring of core/shell nanofibers can be of interest for the development of active antimicrobial surfaces.

Solid Separation from a Mixed Suspension through Electric-Field-Enhanced Crystallization.

When applied to a pure component suspension in an apolar solvent, a strong inhomogeneous electric field induces particle movement, and the particles are collected at the surface of one of the two electrodes. This new phenomenon was used to separately isolate two organic crystalline compounds, phenazine and caffeine, from their suspension in 1,4-dioxane. First, crystals of both compounds were collected at different electrodes under the influence of an electric field. Subsequent cooling crystallization enabled the immobilization and growth of the particles on the electrodes, which were separately collected after the experiment with purities greater than 91 %. This method can be further developed into a technique for crystal separation and recovery in complex multicomponent suspensions of industrial processes.

Fabrication of 3D Polycaprolactone Macrostructures by 3D Electrospinning.

Building 3D electrospun macrostructures and monitoring the biological activities inside them are challenging. In this study, 3D fibrous polycaprolactone (PCL) macrostructures were successfully fabricated using in-house 3D electrospinning. The main factors supporting the 3D self-assembled nanofiber fabrication are the H3PO4 additives, flow rate, and initial distance. The effects of solution concentration, solvent, H3PO4 concentration, flow rate, initial distance, voltage, and nozzle speed on the 3D macrostructures were examined. The optimal conditions of 4 mL/h flow rate, 4 cm initial nozzle-collector distance, 14 kV voltage, and 1 mm/s nozzle speed provided a rapid buildup of cylinder macrostructures with 6 cm of diameter, reaching a final height of 16.18 ± 2.58 mm and a wall thickness of 3.98 ± 1.01 mm on one perimeter with uniform diameter across different sections (1.40 ± 1.10 µm average). Oxygen plasma treatment with 30-50 W for 5 min significantly improved the hydrophilicity of the PCL macrostructures, proving a suitable scaffold for in vitro cell cultures. Additionally, 3D images obtained by synchrotron radiation X-ray tomographic microscopy (SRXTM) presented cell penetration and cell growth within the scaffolds. This breakthrough in 3D electrospinning surpasses current scaffold fabrication limitations, opening new possibilities in various fields.

A vertical additive-lathe printing system for the fabrication of tubular constructs using gelatin methacryloyl hydrogel.

Reproducing both the mechanical and biological performance of native blood vessels remains an ongoing challenge in vascular tissue engineering. Additive-lathe printing offers an attractive method of fabricating long tubular constructs as a potential vascular graft for the treatment of cardiovascular diseases. Printing hydrogels onto rotating horizontal mandrels often leads to sagging, resulting in poor and variable mechanical properties. In this study, an additive-lathe printing system with a vertical mandrel to fabricate tubular constructs is presented. Various concentrations of gelatin methacryloyl (gelMA) hydrogel were used to print grafts on the rotating mandrel in a helical pattern. The printing parameters were selected to achieve the bonding of consecutive gelMA filaments to improve the quality of the printed graft. The hydrogel filaments were fused properly under the action of gravity on the vertical mandrel. Thus, the vertical additive-lathe printing system was used to print uniform wall thickness grafts, eliminating the hydrogel sagging problem. Tensile testing performed in both circumferential and longitudinal direction revealed that the anisotropic properties of printed gelMA constructs were similar to those observed in the native blood vessels. In addition, no leakage was detected through the walls of the gelMA grafts during burst pressure measurement. Therefore, the current printing setup could be utilized to print vascular grafts for the treatment of cardiovascular diseases.

Highly-Controlled Soft-Templating Synthesis of Hollow ZIF-8 Nanospheres for Selective CO2 Separation and Storage.

Global warming is an ever-rising environmental concern, and carbon dioxide (CO2) is among its major causes. Different technologies, including adsorption, cryogenic separation, and sequestration, have been developed for CO2 separation and storage/utilization. Among these, carbon capture using nano-adsorbents has the advantages of excellent CO2 separation and storage performance as well as superior heat- and mass-transfer characteristics due to their large surface area and pore volume. In this work, an environmentally friendly, facile, bottom-up synthesis of ZIF-8 hollow nanospheres (with reduced chemical consumption) was developed for selective CO2 separation and storage. During this soft-templating synthesis, a combined effect of ultra-sonication and low-temperature hydrothermal synthesis showed better control over an oil-in-water microemulsion formation and the subsequent growth of large-surface-area hollow ZIF-8 nanospheres having excellent particle size distribution. Systematic studies on the synthesis parameters were also performed to achieve fine-tuning of the ZIF-8 crystallinity, hollow structures, and sphere size. The optimized hollow ZIF-8 nanosphere sample having uniform size distribution exhibited remarkable CO2 adsorption capability (∼2.24 mmol g-1 at 0 °C and 1.75 bar), a CO2/N2 separation selectivity of 12.15, a good CO2 storage capacity (1.5-1.75 wt %), and an excellent cyclic adsorption/desorption performance (up to four CO2 adsorption/desorption cycles) at 25 °C. In addition, the samples showed exceptional structural stability with only ∼15% of overall weight loss up to 600 °C under a nitrogen environment. Therefore, the hollow ZIF-8 nanospheres as well as their highly controlled soft-templating synthesis method reported in this work are useful in the course of the development of nanomaterials with optimized properties for future CO2 capture technologies.

Multi-Modal Portable Respiratory Rate Monitoring Device for Childhood Pneumonia Detection.

Accurate assessment of Respiratory Rate (RR) is the most important mechanism in detecting pneumonia in low-resource settings. Pneumonia is a disease with one of the highest mortality rates among young children under five. However, the diagnosis of pneumonia for infants remains challenging, especially in low- and middle-income countries (LMIC). In such situations, RR is most often measured manually with visual inspection. Accurate RR measurement requires the child to remain calm without any stress for a few minutes. The difficulty in achieving this with a sick child in a clinical environment can result in errors and misdiagnosis, even more so when the child is crying and non-cooperating around unfamiliar adults. Therefore, we propose an automated novel RR monitoring device built with textile glove and dry electrodes which can make use of the relaxed posture when the child is resting on the carer's lap. This portable system is non-invasive and made with affordable instrumentation integrated on customized textile glove. The glove has multi-modal automated RR detection mechanism that simultaneously uses bio-impedance and accelerometer data. This novel textile glove with dry electrodes can easily be worn by a parent/carer and is washable. The real-time display on a mobile app shows the raw data and the RR value, allowing a healthcare professional to monitor the results from afar. The prototype device has been tested on 10 volunteers with age variation of 3 years to 33 years, including male and female. The maximum variation of measured RR with the proposed system is ±2 compared to the traditional manual counting method. It does not create any discomfort for either the child or the carer and can be used up to 60 to 70 sessions/day before recharging.

Comparison of Nozzle-Based and Nozzle-Free Electrospinning for Preparation of Fast-Dissolving Nanofibers Loaded with Ciprofloxacin.

The study aimed to prepare ciprofloxacin-loaded polyvinylpyrrolidone electrospun nanofibers for oral drug delivery, using a conventional nozzle-based and a lab-built nozzle-free electrospinning equipment. To produce nanofibers, electrospinning is the process most often used. However, from the industry's point of view, conventional electrospinning does not have sufficiently high productivity. By omitting the nozzle, productivity can be increased, and so the development of nozzle-free processes is worthwhile. In this study, a solution of ciprofloxacin and polyvinylpyrrolidone was electrospun under similar conditions, using both single-nozzle and nozzle-free methods. The two electrospinning methods were compared by investigating the morphological and physicochemical properties, homogeneity, in vitro drug release, and cytotoxicity. The stability of the nanofibers was monitored from different aspects in a 26 month stability study. The results showed that the use of the nozzle-free electrospinning was preferable due to a higher throughput, improved homogeneity, and the enhanced stability of nanofiber mats, compared to the nozzle-based method. Nevertheless, fast dissolving nanofibers loaded with poorly water-soluble ciprofloxacin were produced by both electrospinning methods. The beneficial properties of these nanofibers can be exploited in innovative drug development; e.g., nanofibers can be formulated into orodispersible films or per os tablets.

New tricks of old drugs: Repurposing non-chemo drugs and dietary phytochemicals as adjuvants in anti-tumor therapies.

Combination therapy has long been applied to enhance therapeutic effect and deal with the occurrence of multi-drug resistance in cancer treatment. However, the overlapping toxicity of multiple anticancer drugs to healthy tissues and increasing financial burden on patients emerged as major concerns. As promising alternatives to chemo agents, repurposed non-chemo drugs and dietary phytochemicals have been investigated as adjuvants to conventional anti-tumor therapeutics, offering a safe and economic strategy for combination therapy. In this review, we aim to highlight the advances in research about combination therapy using conventional therapeutics and repurposed drugs or phytochemicals for an enhanced anti-tumor efficacy, along with the mechanisms involved in the synergism. Beyond these, we outlined the potential challenges and solutions for clinical translation of the proposed combination therapy, providing a safe and affordable strategy to improve the reach of cancer therapy to low income regions with such new tricks of old drugs.

Recent advancements in the bioprinting of vascular grafts.

Recent advancements in the bioinks and three-dimensional (3D) bioprinting methods used to fabricate vascular constructs are summarized herein. Critical biomechanical properties required to fabricate an ideal vascular graft are highlighted, as well as various testing methods have been outlined to evaluate the bio-fabricated grafts as per the Food and Drug Administration (FDA) and International Organization for Standardization (ISO) guidelines. Occlusive artery disease and cardiovascular disease are the major causes of death globally. These diseases are caused by the blockage in the arteries, which results in a decreased blood flow to the tissues of major organs in the body, such as the heart. Bypass surgery is often performed using a vascular graft to re-route the blood flow. Autologous grafts represent a gold standard for such bypass surgeries; however, these grafts may be unavailable due to the previous harvesting or possess a poor quality. Synthetic grafts serve well for medium to large-sized vessels, but they fail when used to replace small-diameter vessels, generally smaller than 6 mm. Various tissue engineering approaches have been used to address the urgent need for vascular graft that can withstand hemodynamic blood pressure and has the ability to grow and remodel. Among these approaches, 3D bioprinting offers an attractive solution to construct patient-specific vessel grafts with layered biomimetic structures.

In Vitro Drug Release, Permeability, and Structural Test of Ciprofloxacin-Loaded Nanofibers.

Nanofibers of the poorly water-soluble antibiotic ciprofloxacin (CIP) were fabricated in the form of an amorphous solid dispersion by using poly(vinyl pyrrolidone) as a polymer matrix, by the low-cost electrospinning method. The solubility of the nanofibers as well as their in vitro diffusion were remarkably higher than those of the CIP powder or the physical mixture of the two components. The fiber size and morphology were optimized, and it was found that the addition of the CIP to the electrospinning solution decreased the nanofiber diameter, leading to an increased specific surface area. Structural characterization confirmed the interactions between the drug and the polymer and the amorphous state of CIP inside the nanofibers. Since the solubility of CIP is pH-dependent, the in vitro solubility and dissolution studies were executed at different pH levels. The nanofiber sample with the finest morphology demonstrated a significant increase in solubility both in water and pH 7.4 buffer. Single medium and two-stage biorelevant dissolution studies were performed, and the release mechanism was described by mathematical models. Besides, in vitro diffusion from pH 6.8 to pH 7.4 notably increased when compared with the pure drug and physical mixture. Ciprofloxacin-loaded poly(vinyl pyrrolidone) (PVP) nanofibers can be considered as fast-dissolving formulations with improved physicochemical properties.

Facile fabrication of zeolitic imidazolate framework hollow fibre membranes via a novel scalable continuous fluid circulation process.

A novel continuous fluid circulation system was designed and employed for the impregnation seeding and fabrication of zeolitic imidazolate framework (ZIF) crystals on the internal surface of polymeric hollow fibre membranes. Application of impregnation seeding has been proven effective to decrease crystal size, consequently increasing surface roughness and wettability of the membrane. Evaluation of the as-synthesised membrane demonstrated excellent separation efficiencies (>99%) of surfactant stabilised oil-in-water emulsions. Owing to the simple impregnation strategy assisted by the continuous fluid circulation, the active ZIF layer formed was visibly thinner and denser than typical seeding techniques, hence a high pure water flux of >1150 L m-2 h-1 bar-1 was achieved. The membranes were highly selective and ultra-permeable to water, however, almost impermeable to oils in a water environment, e.g., n-hexane, n-heptane, chloroform and dichloromethane, as well as their emulsion mixtures, with a separation efficiency higher than 99%. Besides, this new continuous fluid circulation method was also found promising for the synthesis of other types of ZIF on hollow fibre membranes.

A modified 3D printer as a hybrid bioprinting-electrospinning system for use in vascular tissue engineering applications.

There is a high demand for small diameter vascular grafts having mechanical and biological properties similar to that of living tissues. Tissue-engineered vascular grafts using current methods have often failed due to the mismatch of mechanical properties between the implanted graft and living tissues. To address this limitation, a hybrid bioprinting-electrospinning system is developed for vascular tissue engineering applications. The setup is capable of producing layered structure from electrospun fibres and cell-laden hydrogel. A Creality3D Ender 3D printer has been modified into a hybrid setup having one bioprinting head and two electrospinning heads. Fortus 250mc and Flashforge Creator Pro 3D printers were used to print parts using acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) polymers. An Arduino mega 2560 and a Ramps 1.4 controller board were selected to control the functions of the hybrid bioprinting setup. The setup was tested successfully to print a tubular construct around a rotating needle.

Graphene Wrapping of Electrospun Nanofibers for Enhanced Electrochemical Sensing.

This paper presents a scalable method of developing ultrasensitive electrochemical biosensors. This is achieved by maximizing sensor conductivity through graphene wrapping of carbonized electrospun nanofibers. The effectiveness of the graphene wrap was determined visually by scanning electron microscopy and chemically by Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction. The sensing performance of different electrode samples was electrochemically characterized using cyclic voltammetry and electrochemical impedance spectroscopy, with the graphene-wrapped carbonized nanofiber electrode showing significantly improved performance. The graphene-wrapped carbonized nanofibers exhibited a relative conductivity of ∼14 times and an electroactive surface area of ∼2 times greater compared to the bare screen-printed carbon electrode despite experiencing inhibitive effects from the carbon glue used to bind the samples to the electrode. The results indicate potential for a highly conductive, inert sensing platform.

Design and development of a nozzle-free electrospinning device for the high-throughput production of biomaterial nanofibers.

This technical note provides a step-by-step guide for the design and construction of a temperature-controlled nozzle-free electrospinning device. The equipment uses a rotating mandrel partially immersed within a polymer solution to produce fibers in an upward motion by inducing the formation of multiple Taylor cones and subsequently multi-jetting out of an electrified open surface. Free-surface electrospinning can overcome limitations and drawbacks associated with single and multi-nozzle spinneret configurations, such as low yield, limited production capacity, nonuniform electric field distribution, and clogging. Most importantly, this lab-scaled high-throughput device can provide an alternative economical route for needleless electrospinning research, in contrast to the high costs associated with industrially available upscaling equipment. Among the device's technical specifications, a key feature is a cryo-collector mandrel, capable of collecting fibers in sub-zero temperatures, which can induce ultra-porous nanostructures, wider pores, and subsequent in-depth penetration of cells. A multi-channel gas chamber allows the conditioning of the atmosphere, temperature, and airflow, while the chamber's design averts user exposure to the high-voltage components. All the Computer-Aided Design (CAD) files and point-by-point assembly instructions, along with a list of the materials used, are provided.

Fabrication of Piezoelectric Electrospun Termite Nest-like 3D Scaffolds for Tissue Engineering.

A high piezoelectric coefficient polymer and biomaterial for bone tissue engineering- poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP)-has been successfully fabricated into 3D scaffolds using the wet electrospinning method. Three-dimensional (3D) scaffolds have significant advantages for tissue engineering applications. Electrospinning is an advanced method and can fabricate 3D scaffolds. However, it has some limitations and is difficult to fabricate nanofibers into 3D shapes because of the low controllability of porosity and internal pore shape. The PVDF-HFP powders were dissolved in a mixture of acetone and dimethylformamide with a ratio of 1:1 at various concentrations of 10, 13, 15, 17, and 20 wt%. However, only the solutions at 15 and 17 wt% with optimized electrospinning parameters can be fabricated into biomimetic 3D shapes. The produced PVDF-HFP 3D scaffolds are in the cm size range and mimic the structure of the natural nests of termites of the genus Apicotermes. In addition, the 3D nanofiber-based structure can also generate more electrical signals than the conventional 2D ones, as the third dimension provides more compression. The cell interaction with the 3D nanofibers scaffold was investigated. The in vitro results demonstrated that the NIH 3T3 cells could attach and migrate in the 3D structures. While conventional electrospinning yields 2D (flat) structures, our bio-inspired electrospun termite nest-like 3D scaffolds are better suited for tissue engineering applications since they can potentially mimic native tissues as they have biomimetic structure, piezoelectric, and biological properties.

Fabrication of a Wearable Flexible Sweat pH Sensor Based on SERS-Active Au/TPU Electrospun Nanofibers.

Development of wearable sensing platforms is essential for the advancement of continuous health monitoring and point-of-care testing. Eccrine sweat pH is an analyte that can be noninvasively measured and used to diagnose and aid in monitoring a wide range of physiological conditions. Surface-enhanced Raman scattering (SERS) offers a rapid, optical technique for fingerprinting of biomarkers present in sweat. In this paper, a mechanically flexible, nanofibrous, SERS-active substrate was fabricated by a combination of electrospinning of thermoplastic polyurethane (TPU) and Au sputter coating. This substrate was then investigated for suitability toward wearable sweat pH sensing after functionalization with two commonly used pH-responsive molecules, 4-mercaptobenzoic acid (4-MBA), and 4-mercaptopyridine (4-MPy). The developed SERS pH sensor was found to have good resolution (0.14 pH units for 4-MBA; 0.51 pH units for 4-MPy), with only 1 µL of sweat required for a measurement, and displayed no statistically significant difference in performance after 35 days (p = 0.361). Additionally, the Au/TPU nanofibrous SERS pH sensors showed fast sweat-absorbing ability as well as good repeatability and reversibility. The proposed methodology offers a facile route for the fabrication of SERS substrates which could also be used to measure a wide range of health biomarkers beyond sweat pH.

Protein encapsulation by electrospinning and electrospraying.

Given the increasing interest in the use of peptide- and protein-based agents in therapeutic strategies, it is fundamental to develop delivery systems capable of preserving the biological activity of these molecules upon administration, and which can provide tuneable release profiles. Electrohydrodynamic (EHD) techniques, encompassing electrospinning and electrospraying, allow the generation of fibres and particles with high surface area-to-volume ratios, versatile architectures, and highly controllable release profiles. This review is focused on exploring the potential of different EHD methods (including blend, emulsion, and co-/multi-axial electrospinning and electrospraying) for the development of peptide and protein delivery systems. An overview of the principles of each technique is first presented, followed by a survey of the literature on the encapsulation of enzymes, growth factors, antibodies, hormones, and vaccine antigens using EHD approaches. The possibility for localised delivery using stimuli-responsive systems is also explored. Finally, the advantages and challenges with each EHD method are summarised, and the necessary steps for clinical translation and scaled-up production of electrospun and electrosprayed protein delivery systems are discussed.