Core-Liquid-Induced Transition from Coaxial Electrospray to Electrospinning of Low-Viscosity Poly(lactide- -glycolide) Sheath Solution

Co-electrospinning has demonstrated that polymer solutions below the entanglement concentration can be made into fibers as an encapsulated core in an electrospinnable sheath solution containing a carrier/template polymer. The carrier polymer may require removal at a later stage. This work shows for the first time that without increasing the polymer concentration/molecular weight or needing a template polymer, simply infusing a liquid in the core nozzle can cause the sheath polymer solution (viscosity <20 mPa s) to electrospin instead of electrospray in a coaxial electrified jet. Different from coelectrospinning, the core liquid can be a common solvent such as water and does not require a readily electrospinnable carrier polymer. The process was not limited to one core liquid system; infusing solvents and nonsolvents with different properties in the core generated either beaded fibers or continuous fibers from the sheath solution. The process of fiber formation instead of particle breakup was attributed to the relaxation time of the elastic polymer sheath solution becoming longer than the growth rate of the Rayleigh instability in the compound jet upon the infusion of a second solvent in the core. Key parameters of the process included high surface tension of the core liquid (e.g., water and glycerol), high interfacial tension between the core and the sheath liquids, and electrohydrodynamic operating parameters such as flow rate and applied voltage. Given that charge was transferred from the sheath solution to the core liquid, differences in the dielectric constant and electrical conductivity of the core liquids showed little influence on the process. Fibers also formed irrespective of the miscibility and solubility of the solvent, though in the case of a nonsolvent, a lower miscibility was desirable to minimize polymer precipitation at the core–sheath interface. The process was investigated using poly(lactide-co-glycolide) as a model system, with polycaprolactone and polymethylsilsesquioxane systems presented as two additional examples. This work documents new roles of solvents in coaxial electrohydrodynamic processes and presents a useful method to obtain micro- and nanofibers from low-viscosity solutions without using a template polymer

Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis

The PI-3 kinase (PI-3K)/mTOR pathway is critical for cell growth and proliferation. Strategies of antagonising this signaling have proven to be detrimental to cell survival. This observation, coupled with the fact many tumours show enhanced growth signaling, has caused dual inhibitors of PI-3K and mTOR to be implicated in cancer treatment, and have thus been studied across various tumour models. Since PI-3K (class-I)/mTOR pathway negatively regulates autophagy, dual inhibitors of PI-3K/mTOR are currently believed to be autophagy activators. However, our present data show that the dual PI-3K/mTOR inhibition (DKI) potently suppresses autophagic flux. We further confirm that inhibition of Vps34/PI3KC3, the class-III PI-3K, causes the blockade to autophagosome-lysosome fusion. Our data suggest that DKI induces cell death independently of apoptosis and necroptosis, whereas autophagy perturbation by DKI may contribute to cell death. Given that autophagy is critical in cellular homeostasis, our study not only clarifies the role of a dual PI-3K/mTOR inhibitor in autophagy, but also suggests that its autophagy inhibition needs to be considered if such an agent is used in cancer chemotherapy

A 3-dimensional fibre scaffold as an investigative tool for studying the morphogenesis of isolated plant pells.

BACKGROUND: Cell culture methods allow the detailed observations of individual plant cells and their internal processes. Whereas cultured cells are more amenable to microscopy, they have had limited use when studying the complex interactions between cell populations and responses to external signals associated with tissue and whole plant development. Such interactions result in the diverse range of cell shapes observed in planta compared to the simple polygonal or ovoid shapes in vitro. Microfluidic devices can isolate the dynamics of single plant cells but have restricted use for providing a tissue-like and fibrous extracellular environment for cells to interact. A gap exists, therefore, in the understanding of spatiotemporal interactions of single plant cells interacting with their three-dimensional (3D) environment. A model system is needed to bridge this gap. For this purpose we have borrowed a tool, a 3D nano- and microfibre tissue scaffold, recently used in biomedical engineering of animal and human tissue physiology and pathophysiology in vitro. RESULTS: We have developed a method of 3D cell culture for plants, which mimics the plant tissue environment, using biocompatible scaffolds similar to those used in mammalian tissue engineering. The scaffolds provide both developmental cues and structural stability to isolated callus-derived cells grown in liquid culture. The protocol is rapid, compared to the growth and preparation of whole plants for microscopy, and provides detailed subcellular information on cells interacting with their local environment. We observe cell shapes never observed for individual cultured cells. Rather than exhibiting only spheroid or ellipsoidal shapes, the cells adapt their shape to fit the local space and are capable of growing past each other, taking on growth and morphological characteristics with greater complexity than observed even in whole plants. Confocal imaging of transgenic Arabidopsis thaliana lines containing fluorescent microtubule and actin reporters enables further study of the effects of interactions and complex morphologies upon cytoskeletal organisation both in 3D and in time (4D). CONCLUSIONS: The 3D culture within the fibre scaffolds permits cells to grow freely within a matrix containing both large and small spaces, a technique that is expected to add to current lithographic technologies, where growth is carefully controlled and constricted. The cells, once seeded in the scaffolds, can adopt a variety of morphologies, demonstrating that they do not need to be part of a tightly packed tissue to form complex shapes. This points to a role of the immediate nano- and micro-topography in plant cell morphogenesis. This work defines a new suite of techniques for exploring cell-environment interactions

Copolymer Composition and Nanoparticle Configuration Enhance in vitro Drug Release Behavior of Poorly Water-soluble Progesterone for Oral Formulations

HYPOTHESIS: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone. EXPERIMENTS: ix formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior. FINDINGS: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1± 54.8 to 588.0± 92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9± 1.4% and 70.7± 3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0± 1.7% and 57.5± 2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro

Automorphisms of graphs of cyclic splittings of free groups

We prove that any isometry of the graph of cyclic splittings of a finitely generated free group $F_N$ of rank $N\ge 3$ is induced by an outer automorphism of $F_N$. The same statement also applies to the graphs of maximally-cyclic splittings, and of very small splittings.Comment: 22 pages, 5 figures. Small modifications. To appear in Geometriae Dedicat

Preparation of polymeric nanoparticles by novel electrospray nanoprecipitation

Polymeric nanoparticles have important applications in drug delivery, biotechnology, diagnostics and energy harvesting. We report a new technique named electrospray nanoprecipitation, which combines electrospray with agitated solvent displacement. The process enables one-step formation of polymeric nanoparticles <100 nm in size that are near-monodisperse with a diameter range significantly lower than could be obtained using either electrospray or agitated solvent displacement technique alone. Both reduction of polymer solution concentration and the addition of poly(vinyl alcohol) emulsifier in the water–non-solvent medium further reduce the average particle diameter. The technique provides an effective and straightforward method to further reduce the size range of near-monodisperse nanoparticles achievable in a single step, which can be readily adapted for reducing the achievable size range of core–shell structures using popular one-step encapsulation techniques such as coaxial electrospray. © 2014 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

PEEK surface modification by fast ambient-temperature sulfonation for bone implant applications

We develop a simple, fast and economical surface treatment under ambient temperature to improve the hydrophilicity and osteoconductivity of polyetheretherketone (PEEK) for bone implant applications. A major challenge in bone implants is the drastic difference in stiffness between traditional implant materials (such as titanium and stainless steel) and human bone. PEEK is biocompatible with an elastic modulus closely matching that of human bone, making it a highly attractive alternative. However, its bio-inert and poorly hydrophilic surface presents a serious challenge for osseointegration. Sulfonation can improve hydrophilicity and introduce bioactive sulfonate groups, but PEEK sulfonation has traditionally been applied for fuel cells, employing elevated temperatures and long reaction times to re-cast PEEK into sulfonated films. Little research has systematically studied PEEK surface modification by short reaction time (seconds) and ambient-temperature sulfonation for biomedical applications. Here, we investigate three ambient-temperature sulfonation treatments under varying reaction times (5–90 s) and evaluate the hydrophilicity and morphology of 15 modified PEEK surfaces. We establish an optimal treatment using 30 s H₂SO₄ followed by 20 s rinsing, and then 20 s immersion in NaOH followed by 20 s rinsing. This 30 s ambient-temperature sulfonation is found to be more effective than conventional plasma treatments and reduced PEEK water contact angle from 78° to 37°

A coating-free superhydrophobic sensing material for full-range human motion and microliter droplet impact detection

Traditional waterproofing strategies (e.g. plastic seals, superhydrophobic coatings) of strain sensors greatly limit their sensing performance (e.g., sensitivity, working-range, and working-life). Here a unique ultra-stretchable, coating-free superhydrophobic material is developed for high-performence strain sensing in harsh environments. This material integrates high sensitivity (GF of 2.1 to 214), wide sensing range (up to 447% strain), low resolution (<0.2% strain), dynamic durability (over 10,000 stretching cycles at 50% strain), and ultra-robust superhydrophobicity (mechanically, chemically, thermally, and UV impervious) in a single system, outperforming most of reported waterproof sensors. Such remarkable sensing materials can detect full range human movement, pulse rate and vocal fold vibration. The sensing material is designed to be superhydrophobic throughout its bulk material for work in harsh environments (water, corrosive liquid, high humidity, etc.). More importantly, the superhydrophobicity enables the highly sensitive sensor to detect microliter droplets impact with minimized energy loss. Thus, this sensing material should find many potential applications in wearable electronics, measurement platform, rainfall monitoring and intelligent irrigation system

Preparation of porous microsphere-scaffolds by electrohydrodynamic forming and thermally induced phase separation.

The availability of forming technologies able to mass produce porous polymeric microspheres with diameters ranging from 150 to 300 μm is significant for some biomedical applications where tissue augmentation is required. Moreover, appropriate assembly of microspheres into scaffolds is an important challenge to enable direct usage of the as-formed structures in treatments. This work reports the production of poly (glycolic-co-lactic acid) and poly (ε-caprolactone) microspheres under ambient conditions using one-step electrohydrodynamic jetting (traditionally known as atomisation) and thermally induced phase separation (TIPS). To ensure robust production for practical uses, this work presents 12 comprehensive parametric mode mappings of the diameter distribution profiles of the microspheres obtained over a broad range of key processing parameters and correlating of this with the material parameters of 5 different polymer solutions of various concentrations. Poly (glycolic-co-lactic acid) (PLGA) in Dimethyl carbonate (DMC), a low toxicity solvent with moderate conductivity and low dielectric constant, generated microspheres within the targeted diameter range of 150-300 μm. The fabrication of the microspheres suitable for formation of the scaffold structure is achieved by changing the collection method from distilled water to liquid nitrogen and lyophilisation in a freeze dryer

Dimensionality and dynamics in the behavior of C. elegans

A major challenge in analyzing animal behavior is to discover some underlying simplicity in complex motor actions. Here we show that the space of shapes adopted by the nematode C. elegans is surprisingly low dimensional, with just four dimensions accounting for 95% of the shape variance, and we partially reconstruct "equations of motion" for the dynamics in this space. These dynamics have multiple attractors, and we find that the worm visits these in a rapid and almost completely deterministic response to weak thermal stimuli. Stimulus-dependent correlations among the different modes suggest that one can generate more reliable behaviors by synchronizing stimuli to the state of the worm in shape space. We confirm this prediction, effectively "steering" the worm in real time.Comment: 9 pages, 6 figures, minor correction