Efrosyni Themistou

Nile Blue-Based Nanosized pH Sensors for Simultaneous Far-Red and Near-Infrared Live Bioimaging

Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid cell uptake for a wide range of cell lines, while the PDPA block constitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible vesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In addition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in fluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce a highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by cells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/hydrophobic balance.

Targeting Siglecs with a sialic acid–decorated nanoparticle abrogates inflammation

A nanoparticle coated with sialic acid activates Siglec receptors on macrophages, improving survival from sepsis in mice and reducing inflammation in human tissues. Stopping sepsis Sepsis is a dreaded diagnosis; clinicians have few tools to fight this generalized inflammatory response to infection that too often results in death. A new nanoparticle described by Spence et al. may prove to be a welcome weapon in the antisepsis arsenal. The nanoparticles are coated with di(α2→8) N-acetylneuraminic acid (NANA), which mimics sialic acid, the natural ligand for a critical anti-inflammatory receptor found on macrophages. This so-called Siglec receptor (sialic acid–binding immunoglobulin-like lectin-E) down-regulates macrophage activation by inflammatory signals released during infection and tissue damage, thereby interrupting the chain of events leading to sepsis. The authors demonstrate that the nanoparticle boosts this anti-inflammatory response in culture, and also show that it improves survival in two mouse models of generalized sepsis and one of pulmonary injury. Most encouraging for the ultimate utility of this nanoparticle in human patients, the nanoparticle is effective in human macrophages and in a sophisticated ex vivo model of human lung edema. Sepsis is the most frequent cause of death in hospitalized patients, and severe sepsis is a leading contributory factor to acute respiratory distress syndrome (ARDS). At present, there is no effective treatment for these conditions, and care is primarily supportive. Murine sialic acid–binding immunoglobulin-like lectin-E (Siglec-E) and its human orthologs Siglec-7 and Siglec-9 are immunomodulatory receptors found predominantly on hematopoietic cells. These receptors are important negative regulators of acute inflammatory responses and are potential targets for the treatment of sepsis and ARDS. We describe a Siglec-targeting platform consisting of poly(lactic-co-glycolic acid) nanoparticles decorated with a natural Siglec ligand, di(α2→8) N-acetylneuraminic acid (α2,8 NANA-NP). This nanoparticle induced enhanced oligomerization of the murine Siglec-E receptor on the surface of macrophages, unlike the free α2,8 NANA ligand. Furthermore, treatment of murine macrophages with these nanoparticles blocked the production of lipopolysaccharide-induced inflammatory cytokines in a Siglec-E–dependent manner. The nanoparticles were also therapeutically beneficial in vivo in both systemic and pulmonary murine models replicating inflammatory features of sepsis and ARDS. Moreover, we confirmed the anti-inflammatory effect of these nanoparticles on human monocytes and macrophages in vitro and in a human ex vivo lung perfusion (EVLP) model of lung injury. We also established that interleukin-10 (IL-10) induced Siglec-E expression and α2,8 NANA-NP further augmented the expression of IL-10. Indeed, the effectiveness of the nanoparticle depended on IL-10. Collectively, these results demonstrated a therapeutic effect of targeting Siglec receptors with a nanoparticle-based platform under inflammatory conditions.

Controlling surface topology and functionality of electrospun fibers on the nanoscale using amphiphilic block copolymers to direct mesenchymal progenitor cell adhesion.

Surface patterning in three dimensions is of great importance in biomaterials design for controlling cell behavior. A facile one-step functionalization of biodegradable PDLLA fibers using amphiphilic diblock copolymers is demonstrated here to systematically vary the fiber surface composition. The copolymers comprise a hydrophilic poly[oligo(ethylene glycol) methacrylate] (POEGMA), poly[(2-methacryloyloxy)ethyl phosphorylcholine] (PMPC), or poly[2-(dimethylamino)ethyl methacrylate)] (PDMAEMA) block and a hydrophobic poly(l-lactide) (PLA) block. The block copolymer-modified fibers have increased surface hydrophilicity compared to that of PDLLA fibers. Mixtures of PLA-PMPC and PLA-POEGMA copolymers are utilized to exploit microphase separation of the incompatible hydrophilic PMPC and POEGMA blocks at the fiber surface. Conjugation of an RGD cell-adhesive peptide to one hydrophilic block (POEGMA) using thiol-ene chemistry produces fibers with domains of cell-adhesive (POEGMA) and cell-inert (PMPC) sites, mimicking the adhesive properties of the extracellular matrix (ECM). Human mesenchymal progenitor cells (hES-MPs) showed much better adhesion to the fibers with surface-adhesive heterogeneity compared to that to fibers with only adhesive or only inert surface chemistries.

Nanoscale detection of metal-labeled copolymers in patchy polymersomes

We report the synthesis of polymersome-forming block copolymers using two different synthetic routes based on Atom Transfer Radical Polymerization (ATRP) and Reversible Addition Fragmentation chain Transfer (RAFT) polymerization, respectively. Functionalization with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) allowed the block copolymer chains to be labelled with electron-dense metal ions (e.g. indium). The resulting metal-conjugated copolymers can be visualized by transmission electron microscopy with single chain resolution, hence enabling the study of polymer/polymer immiscibility and phase separation on the nano-scale.

Polyelectrolyte nanocages via crystallized miniemulsion droplets

Polyelectrolyte nanocages were synthesized by interfacial cross-linking of monolayers of vinyl-functionalized surfactant molecules adsorbed by crystallized miniemulsion droplets. The monolayer-thick shell of these nanocages was confirmed by AFM analysis.

pH-Responsive diblock copolymers with two different fluorescent labels for simultaneous monitoring of micellar self-assembly and degree of protonation

We report the synthesis of a novel amphiphilic pH-responsive diblock copolymer labeled with two different fluorophores. This copolymer comprises a water-soluble poly(glycerol monomethacrylate) [PGMA] block and a pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) [PDPA] block. Pyrene methacrylate [PyMA] is statistically copolymerized with glycerol monomethacrylate (GMA) to introduce a suitable fluorescent label. The chain-ends of the PDPA block are labelled using cresyl violet perchlorate [CV] by exploiting the spin trap properties of this dye molecule. Below pH 6, fluorescence from both dye labels can be detected, but deprotonation of the PDPA block between pH 6 and 7 leads to strong attenuation of the CV fluorescence owing to formation of a charge transfer complex with the tertiary amine units in the PDPA block. Therefore, changes in the Cresyl Violet fluorescence intensity can be correlated to changes in PDPA protonation. Diblock copolymer self-assembly to form PDPA-core aggregates occurs under these conditions, leading to pyrene fluorescence at an excitation wavelength of 405 nm. This allows direct measurement of chain aggregation, whereas using pH-responsive dyes is simply a measure of the degree of protonation. Here we focus on the synthesis and characterisation of dual-labeled copolymers and their spectroscopic properties in different environments. Finally, we show that using CV as a spin trap provides a convenient and versatile route to fluorescently-labeled copolymers prepared by either RAFT or ATRP. Moreover, this cost-effective dye fluoresces in the red part of the visible spectrum at both neutral and acidic pH.

Functionalized well-defined polymeric nanostructures for biomedical applications

D of biodegradable materials is highly in demand as large and rapid usage of plastic materials results million tons of plastic wastes in the landfill sites each year globally. It takes a long time for conventional plastics to degrade, leading to severe ecological problems too. The production capacities of biodegradable plastics, such as polylactic acid (PLA), polyhydroxyalkanoates, and starch blends, are also growing steadily, nearly doubling from 0.7 million metric tons in 2014 to well over 1.2 million metric tons by 2019. PLA, for its good compatibility and biodegradability, is preferred by people from all sectors. Also, PLA is a low energy consumption product, about 30-50% lower in energy consumption than the petroleum-based polymers. PLA as the most widely used, the lowest price of bioplastic in industrialization, in the aspect of practicality, is the biodegradable material that has the largest scope to replace the position of the petroleum based plastics on the current scenario of oil scarcity. The production cost of PLA is also approaching the cost of traditional plastic, and with the strong expansion of market applications, will get soon recognized globally. PLA based nanocomposites are widely used today in various applications. The review article aims to target on the topical progresses in the synthesis and characterization of PLA blends, PLA composites and PLA nanocomposites with different materials. Moreover, this article is a unique collection of vital information about PLA based blends and composites for drug delivery, packaging and barrier applications in a single platform.D intensive research and applications of different techniques to improve surface properties of vascular stents, currently available metal stents and their coatings (DES drug eluting stents) still lack of desired surface biocompatibility, mostly due to mechanical injuries, inflammation, as well as proliferation and migration of smooth muscle cells, often with progression to restenosis. Besides, the durability and stability of DES is still problematic and has been connected with high risk of thrombosis Biomimetic nanosized materials, with their crystal structure, surface morphology and chemical properties are one of critical features for their potential use in vascular stent applications, which should support adhesion, proliferation and differentiation of endothelial cells and prevent abnormal growth of smooth muscle cells. For example, it was shown that titanium dioxide (TiO2) nanotubes (NTs) topography is essential parameter in optimizing endothelial cell and smooth muscle cell responses to vascular implants. The purpose of this study is to investigate surface properties and crystal structure of TiO2 NTs. Since the oxygen, plasma treatment plays significant role in surface treatment of biomedical devices due to surface cleaning and sterilization, its effect on the mechanical stability and surface chemical properties was evaluated. Vertically aligned arrays of TiO2 NTs were synthesized on Ti metallic substrates with electrochemical anodization. The crystal structure was investigated with X-ray Diffraction Spectroscopy, while morphology and surface properties were analyzed with Scanning Electron Microscopy coupled with Energy Dispersive X-ray Analysis, X-ray Photoelectron Spectroscopy and Water Contact Angle analysis. Our results indicate that oxygen plasma treatment of TiO2 NTs surfaces induces the formation of oxide layer on the surface of TiO2 NT, which could result in enhanced biocompatibility. Moreover, plasma treatment removes undesired electrolyte residues on TiO2 NTs surface and highly improves its wettability. We showed that plasma treated TiO2 NTs possess long-term hydrophilicity and influence on crystallization of amorphous TiO2 NTs to anatase and/or rutile crystal phase, which could be the reason for improved wettability. The optimized conditions (power, frequency and time) of oxygen plasma treatment on the mechanical stability of TiO2 NTs are also presented. Oxygen plasma treatment can greatly improve the surface characteristics of biomimetic materials and enhance their biocompatibility. Restenosis and thrombosis still remain a serious concern and should be given a great deal of attention in order to produce improved tissue-material response.Resumen del trabajo presentado a la 11th International Conference on Advanced Materials & Processing, celebrada en Edimburgo (Escocia) del 7 al 8 de septiembre de 2017.P of thin lead zirconate titanate (PZT) films on metallic substrates has several advantages such as high frequency operation, low electrical series resistance, low dielectric loss and potential for embedded capacitor systems. As a suitable metal support for PZT films, titanium (Ti) seems to be the most natural choice as it possess high melting point, the thermal expansion coefficient of Ti matches closely to that of PZT and permits good adhesion with low reactivity. However, ferroelectric and piezoelectric responses of PZT films on Ti substrates are found to be not that encouraging. Presence of a non-ferroelectric pyrochlore/ fluorite (Py/Fl) phase on the surface of the PZT film is believed to be the primary cause for poor electrical performance. In this work, effect of re-crystallization of PZT films with a thin Pb-overcoat has been investigated though structural, morphological, compositional and electrical studies. Sputter deposited PZT thin films on Ti-substrates are found to contain a Pb-deficient and Zr-enriched Py/Fl phase of type Pb2 (Zr,Ti)2O6 on the surface of the PZT film. Re-crystallization of these PZT films with a thin lead (Pb) overcoat improves the degree of crystallization, morphology and dielectric/ Ferroelectric properties of the films by converting the top Pb-lean and Zr-rich Py/Fl phase into perovskite phase. Structural changes that occur in PZT films upon re-crystallization with a Pb-overcoat have been correlated with ferroelectric characteristics of the PZT films.P nanoparticles have a broad spectrum of applications including dispersion (emulsion) paints or thin films. However, the understanding of their behavior and properties, especially at high concentrations is still limited. We model the dispersions of polymeric nanoparticles using the dynamic model based on Discrete Element Method (DEM). The interaction model represents particles that are elastic, adhesive and electrostatically stabilized. The flow-field computation that is included in the model enables us to evaluate the rheological properties of the dispersion, which are crucial for its behavior. Further characterization of both dispersions and gels is done using oscillatory simulations, from which the viscoelastic properties are obtained. The model was successfully used to describe the dynamic behavior of a flowing dispersion including the processes of coagulation, fouling and breakage. These processes and their relative importance in a specific system determine the transition from a dispersed state to a gel. Due to their specific position on the boundary between solids and liquids, gels have unique properties that make them suitable to be used e.g., as a porous structures (or) matrices for drug delivery in the pharmaceutical industry.O surgery has grown from the hand of new materials that made possible to perform procedures as total hip replacement with feasibility. These procedures are common in most orthopaedic departments, and more than 70 000 hip or knee replacements are performed in Spain every year. The survival of these implants is critical to prevent loosening and the need for revision arthroplasty. The ideal surface to interact with bone has not been created. We created laser induced periodic surface structures (LIPSS) in the surface of titanium and tantalium to study the behaviour of stem cells compared to polished surfaces. We created 12 discs of each material and polished them. Later we created LIPSS in 6 discs of each material. We cultured them in human stem cells in a concentration of 25000 cell per cm2 for 20 days. We determined MTT, TNF-Alfa, alkaline phosphatase, IL-6, osteopontin and osteocalcin every 5 days until the day 20. We confirmed outcomes behave as a normal distribution after applying the Kolmogorov Smirnov test. We compared materials and surfaces with the T-student test. We accepted a difference of 0.05 as significant. LIPSS created increase statistically cell metabolism (best values in MTT assay) and decrease inflammatory response to the material (IL-6 and TNF-alfa values). Collagen is produced in more quantity and cells differentiate to osteoblast easily. These differences are seen from the beginning until the endpoint (day 20). When LIPSS improved osteogenic properties of titanium and tantalium compared to smooth surfaces.I the last 5 years, methylammonium lead halide or MALH perovskites (e.g., CH3NH3PbA3-xBx, where A and B are I, Cl or Br) have shown tremendous potential for low-cost optoelectronic device integration, including light-emitting diodes, solar cells and photodetectors. For example, the power-conversion efficiencies from organometallic halide perovskite solar cells have increased from 3.8% in 2009 to 22.1% in 2016. This spectacular progress is largely attributed to improved processing and longer chargecarrier lifetimes, directly related to increased material quality. While significant progress was made, many key parameters including compatibility, interface engineering, surface treatment and processability remain essential to achieving the best device performances. These fundamental challenges prevent integration into commercial-grade devices. For one, relatively low carrier mobilities still prevent large-area devices with performances competing with state-of-the-art technologies. Several groups began exploring hybrid perovskite films in the last 3 years. In the last year, we have made major progress towards viable MALH devices (1) by dramatically enhancing structure and properties through solvent engineering, (2) enhancing conductivities by several orders of magnitude using MALH hybrids, (3) extending their operation to the near-infrared and (4) significantly improving their stability and lifetime by doping with SCN. Preliminary results shown in Fig.1 are greatly encouraging and suggest that the carefully-controlled processing capability allowed by the Ceradrop inkjet printer can yield high-quality MALH films. This is a major step towards the integration of MALH perovskites within commercial printable photovoltaic devices, LEDs and sensors.C normally causes damage in hydraulic machineries such as pumps and screw propellers, as severe impacts are produced at cavitation collapses. However, cavitation impacts can be utilized for surface mechanics design for improvement of fatigue strength in the same way of shot peening. The peening method using cavitation impacts is named as “cavitation peening”. The advantage of cavitation peening is that the increase of surface roughness is small comparing with conventional shot peening, as shots are not required in cavitation peening. In order to mitigate stress corrosion cracking, introduction of compressive residual using cavitation impact was proposed, and it has been applied for nuclear power plants. By enhancing cavitation impacts, improvement of fatigue strength was demonstrated.The aspect of cavitation peening of gear by using a submerged water jet with cavitation, i.e., a cavitating jet. In order to investigate mechanism of improvement of fatigue strength, a special fatigue tester was developed to investigate crack propagation in surface modified layer. Cavitation peening also suppress hydrogen embrittlement. At laser peening, it is believed that impact caused by laser abrasion produces plastic deformation for surface treatment. However, a bubble is generated after laser abrasion, and it produces impact at bubble collapse like cavitation, then it can be called as laser cavitation. As shown in Fig. 2, when the impact passing through the material was measured, the impact induced by laser abrasion is larger than that of laser abrasion. Namely, at submerged laser peening, peening effect would be improved by considering the laser cavitation. In the presentation, the principal of cavitation peening is introduced with applications of cavitation peening such as improvement of fatigue strength and suppression of hydrogen embrittlement. The work was partly supported by Osawa Scientific Studies Grants Foundation.E of materials subjected to electric current and Joule heating has been studied by many researchers and fruitful results have been reported. In my presentation, crack problems in a conductive material are first discussed. The path-independent integral for an electric crack problem in a plate subjected to current is explained with its relations to Joule heating near the crack tip and the increase in electric resistance of the plate due to a unit crack extension. Regarding nondestructive evaluation of cracks, highly sensitive direct current potential drop technique, that is closely coupled probes potential drop (CCPPD) technique, is explained with its principle and superior characteristics for evaluation of closed cracks. Also evaluation of multiple cracks is mentioned. In the second, a topic in the field of micro and nano materials evaluation is explained, which is a subject of electrical failure of a metallic nanowire mesh due to Joule heating. Characteristic nature of sequential melting of nanowires in the mesh is explained for respective conditions of current control and voltage control. Next, electromigration (EM) phenomenon, which is atomic diffusion due to electron flow in high density, in metallic thin-film materials related to reliability of integrated circuits is discussed, where the effect of passivation on damage suppression is focused. Finally, fabrication of micro materials of wire and sphere is explained as utilization of EM, where the effect of temperature caused by Joule heating on the shape of formed micro material is mentioned. In addition, the other phenomena of atomic migration such as stress migration and ionic migration are discussed in comparison with EM from a few points of view. Electric field and Joule heating are connected with materials science and evaluation on many equipments, machines and structures. As written above, four topics related to these physical quantities are reviewed in this presentation.D the rapid evolution of material science, it remains difficult to deploy new polymers that are inadequate to meet the stringent demands of industrial membrane separations. Polymer membranes must be ultrapermeable, selective, and resistant to both physical aging, and plasticization. Polymers with intrinsic microporosity (PIMs) are ultrapermeable, yet vulnerable to physical aging and plasticization. Here we show that aging and plasticization in PIMs can be switched on and off through compatibility with a microporous polymer, porous aromatic frameworks (PAFs). By replacing bulky methyl groups with smaller hydro groups, we remove the ability of a PIM polymer matrix to interact with PAFs; accelerating both physical aging and plasticization. Meanwhile PAFs tailors physical aging and annihilates plasticization in the original methylated PIM via physical interactions at specific locations on the PIM polymer chains. This benefits hydrogen recovery at realistic operating conditions; enabling the implementation of polymer membranes as a stand-alone separation technology, a paradigm shift from existing hybrid methods.

Amphiphilic block copolymer-based photonic platform towards efficient protein detection

The development of a low complexity fiber optic based protein sensor by functionalizing the surface of silica optical fibers using block copolymers having both hydrophobic poly(methyl methacrylate) (PMMA) and hydrophilic poly[2- (dimethylamino)ethyl methacrylate] (PDMAEMA) blocks is presented here. The amphiphilic thiol-functionalized PMMA117-b-P(DMAEMA17-st-TEMA2) and vinyl-sulfone PMMA117-b-P(DMAEMA17-st-VSTEMA2) block copolymers designed and synthesized in this work contain a cationic hydrophilic PDMAEMA block that can electrostatically bind selected oppositely charged proteins and also appropriate functional groups for reversible or non-reversible protein binding, respectively, leading to a refractive index change of the overlayer and hence, enabling the sensing. The developed PMMA117-b-PDMAEMA16-based platform has been evaluated for bovine serum albumin (BSA) sensing, exhibiting linear response to detected BSA concentrations.