Neural stem cell differentiation by electrical stimulation using a cross-linked PEDOT substrate: Expanding the use of biocompatible conjugated conductive polymers for neural tissue engineering.

BACKGROUND: The use of conjugated polymers allows versatile interactions between cells and flexible processable materials, while providing a platform for electrical stimulation, which is particularly relevant when targeting differentiation of neural stem cells and further application for therapy or drug screening. METHODS: Materials were tested for cytotoxicity following the ISO10993-5. PEDOT: PSS was cross-linked. ReNcellVM neural stem cells (NSC) were seeded in laminin coated surfaces, cultured for 4 days in the presence of EGF (20 ng/mL), FGF-2 (20 ng/mL) and B27 (20 µg/mL) and differentiated over eight additional days in the absence of those factors under 100Hz pulsed DC electrical stimulation, 1V with 10 ms pulses. NSC and neuron elongation aspect ratio as well as neurite length were assessed using ImageJ. Cells were immune-stained for Tuj1 and GFAP. RESULTS: F8T2, MEH-PPV, P3HT and cross-linked PEDOT: PSS (x PEDOT: PSS) were assessed as non-cytotoxic. L929 fibroblast population was 1.3 higher for x PEDOT: PSS than for glass control, while F8T2 presents moderate proliferation. The population of neurons (Tuj1) was 1.6 times higher with longer neurites (73 vs 108 µm) for cells cultured under electrical stimulus, with cultured NSC. Such stimulus led also to longer neurons. CONCLUSIONS: x PEDOT: PSS was, for the first time, used to elongate human NSC through the application of pulsed current, impacting on their differentiation towards neurons and contributing to longer neurites. GENERAL SIGNIFICANCE: The range of conductive conjugated polymers known as non-cytotoxic was expanded. x PEDOT: PSS was introduced as a stable material, easily processed from solution, to interface with biological systems, in particular NSC, without the need of in-situ polymerization.

Vitamin B3 Supplementation for Optic Neuropathies: A Comprehensive Review.

Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.

Graphene Biosensors-A Molecular Approach.

Graphene is the material elected to study molecules and monolayers at the molecular scale due to its chemical stability and electrical properties. The invention of scanning tunneling microscopy has deepened our knowledge on molecular systems through imaging at an atomic resolution, and new possibilities have been investigated at this scale. Interest on studies on biomolecules has been demonstrated due to the possibility of mimicking biological systems, providing several applications in nanomedicine: drug delivery systems, biosensors, nanostructured scaffolds, and biodevices. A breakthrough came with the synthesis of molecular systems by stepwise methods with control at the atomic/molecular level. This article presents a review on self-assembled monolayers of biomolecules on top of graphite with applications in biodevices. Special attention is given to porphyrin systems adsorbed on top of graphite that are able to anchor other biomolecules.

Graphene Oxide Thin Films with Drug Delivery Function.

Graphene oxide has been used in different fields of nanomedicine as a manager of drug delivery due to its inherent physical and chemical properties that allow its use in thin films with biomedical applications. Several studies demonstrated its efficacy in the control of the amount and the timely delivery of drugs when it is incorporated in multilayer films. It has been demonstrated that oxide graphene layers are able to work as drug delivery or just to delay consecutive drug dosage, allowing the operation of time-controlled systems. This review presents the latest research developments of biomedical applications using graphene oxide as the main component of a drug delivery system, with focus on the production and characterization of films, in vitro and in vivo assays, main applications of graphene oxide biomedical devices, and its biocompatibility properties.

Liposomes encapsulating methylene blue and acridine orange: An approach for phototherapy of skin cancer.

Photodynamic therapy uses photosensitizer molecules for the photo-mediated treatment of several diseases such as cancer and skin disorders. However, most of the photosensitizer molecules present problems such as aggregation and low solubility in physiological environments which hinders the treatment efficacy. To overcome these problems, the development of stable liposomes loading photosensitizing molecules as delivery systems can be explored as promising alternatives to enhance cellular uptake and the therapy's efficacy. In this work, liposomes composed by different lipids with or without surfactants were characterized for the encapsulation of photosensitizer molecules such as Methylene Blue (MB) and Acridine Orange (AO). Liposomes were produced by the thin-film hydration method followed by extrusion to reduce particle size and were characterized by Dynamic Light Scattering and Atomic Force Microscopy. Encapsulation efficiency was evaluated as well as the release profile of these molecules from the liposome systems. Cytotoxicity and phototoxicity studies were performed on keratinocytes with and without carcinoma. Results showed that liposome's stability depends on the composition of lipids regardless of the presence of surfactants. Most stable liposomes were those with cholesterol plus the surfactants Span® 80 or sodium cholate that were able to provide higher stability for the liposomes considering the MB and AO encapsulation. Encapsulation efficiency (EE) studies revealed that AO had greater affinity for the vesicles presenting high EE (>98%) while for MB the encapsulation was, in general, moderate (between 63% and 86%). Greater phototoxicity was observed for MET1 squamous cell carcinoma (SCC) cells treated with AO liposomes, achieving similar half-maximal inhibition concentration (IC50) as for the free drug. Finally, two different possible approaches were found, namely, MB-liposomes with potential as a cytotoxic agent for cancer cells; and AO liposomes with a great phototoxicity potential at very low concentrations.

Stepwise preparation and characterization of molecular wires made of zinc octaethylporphyrin complexes bridged by 4,4'-bipyridine on HOPG.

Molecular-scale devices can be made using a step-by-step procedure, in a controllable and highly versatile way. In this report, we describe the growth of molecular wires (MW) from zinc (II) octaethylporphyrin (ZnOEP) assembled on highly oriented pyrolytic graphite (HOPG) by a step-by-step approach using 4,4'-bipyridine (BP) to bridge the porphyrin units, via coordination of the nitrogen atom to zinc. In order to gain an insight into the molecular self-organization of these wires, we carried out a detailed scanning tunnelling microscopy (STM) analysis of each monolayer, using a solid/liquid interface technique, up to a complete ZnOEP/BP/ZnOEP/BP/ZnOEP-assembled structure. The electrical properties of the MWs were assessed by scanning tunnelling spectroscopy (STS) and by current-sensing atomic force microscopy (CS-AFM), showing an increase of electrical resistance with the length of the MW.

Nanopatterning in Langmuir-Blodgett monolayers of a thermoresponsive double hydrophilic block copolymer studied by atomic force microscopy.

The microphase-separation of Langmuir-Blodgett (LB) monolayers of a rhodamine B (RhB) end-labeled double hydrophilic block copolymer (DHBC), RhB-Poly(N,N-dimethylacrylamide)-b-poly(N,N-diethylacryl-amide) (RhB-PDMA(207)b-PDEA177) and the 1:1 segmental mixture of PDEA and RhB-PDMA homopolymers was followed by AFM. The DHBC LB films revealed a loose distribution of nano-aggregates with variable geometries below the lower critical solution temperature (LCST) of PDEA (32 degrees C) and low surface pressure (3 mN m(-1)). By increasing either the temperature above the LCST of PDEA or the surface pressure beyond the immersion regime of PDMA in the subphase (7 mN m(-1)) a dense nanopatterning was obtained. The absence of a corresponding regular nanopatterning in LB films of mixed homopolymers with the same composition highlights the role of the covalent bonding between PDEA and PDMA on the self-segregation of the two blocks at the air-water interface.

Graphene Oxide Layer-by-Layer Films for Sensors and Devices.

Layer-by-layer films of poly (allylamine hydrochloride) (PAH) and graphene oxide (GO) were characterized, looking at growth with the number of bilayers, morphology, and electrical properties. The PAH/GO films revealed a linear increase in absorbance with the increase in the number of deposited bilayers, allowing the determination that 10.7 ± 0.1 mg m-2 of GO is adsorbed per unit of area of each bilayer. GO absorption bands at 146, 210, 247 and 299 nm, assigned to π-π* and n-π* transitions in the aromatic ring (phenol) and of the carboxylic group, respectively, were characterized by vacuum ultraviolet spectroscopy. The morphological characterization of these films demonstrated that they are not completely uniform, with a bilayer thickness of 10.5 ± 0.7 nm. This study also revealed that the films are composed of GO and/or PAH/GO fibers and that GO is completely adsorbed on top of PAH. The electrical properties of the films reveal that PAH/GO films present a semiconductor behavior. In addition, a slight decrease in conduction was observed when films were prepared in the presence of visible light, likely due to the presence of oxygen and moisture that contributes to the damage of GO molecules.

Microphase separation in mixed monolayers of DPPG with a double hydrophilic block copolymer at the air-water interface: a BAM, LSCFM, and AFM study.

Phase separation and interactions in mixed monolayers of dipalmitoylphosphatidylglycerol (DPPG) with the rhodamine B end-labeled double-hydrophilic block copolymer (DHBC), poly(N,N-dimethylacrylamide)-block-poly(N,N-diethylacrylamide) (RhB-PDMA(207)-b-PDEA(177)), was studied at the air-water interface. Surface pressure versus area isotherms indicate that both components behave almost independently. Brewster angle microscopy (BAM) images show a random distribution of liquid condensed (LC) domains of DPPG in an apparent homogeneous matrix of DHBC, excluding the macroscopic phase separation. The laser scanning confocal fluorescence microscopy (LSCFM) of the rhodamine dye at the end of the PDMA chain showed how the DHBC is distributed in Langmuir-Blodgett (LB) mixed monolayers. The high spatial resolution of atomic force microscopy (AFM) combined with the LCSFM images indicates that DHBC incorporates in the expanded phase of DPPG to form mixed domains, being excluded from the condensed regions. Upon compression, nanosized LC domains of DPPG nucleate inside the mixed domains corralled in the nanopatterning of pure DHBC. The negatively charged polar group of DPPG inhibits rhodamine aggregation, while the long polymer chains promote the formation of corralled nanodomains of DPPG in two dimensions.

Bottom-Up Self-Assembled Supramolecular Structures Built by STM at the Solid/Liquid Interface.

One of the lines of research on organic devices is focused on their miniaturization to obtain denser and faster electronic circuits. The challenge is to build devices adding atom by atom or molecule by molecule until the desired structures are achieved. To do this job, techniques able to see and manipulate matter at this scale are needed. Scanning tunneling microscopy (STM) has been the selected technique by scientists to develop smart and functional unimolecular devices. This review article compiles the latest developments in this field giving examples of supramolecular systems monitored and fabricated at the molecular scale by bottom-up approaches using STM at the solid/liquid interface.

Self-Assembled Multilayer Films for Time-Controlled Ocular Drug Delivery.

The patient's compliance on the therapeutics to treat glaucoma is significantly low contributing for a fast evolution of the disease. This article presents an autonomous system with controlled release using an alpha2-adrenergic receptor agonist, brimonidine, usually used to treat glaucoma. More specifically, biocompatible and layer-by-layer drug delivery films containing monolayers with brimonidine encapsulated in polymer-ß-cyclodextrin were prepared with the objective to obtain a system able to release precise amounts of drug at specific times. To delay the erosion-controlled drug release, we included nanosheets of graphene oxide and layers of a biodegradable polymer (poly-ß-aminoester) between the drug-containing monolayers to obtain a time-controlled drug delivery system. An increase in the number of graphene oxide layers is proportional to the brimonidine release delay and its kinetic release can be tuned as a function of the number of layers. Two types of films with brimonidine encapsulated in ß-cyclodextrin were analyzed. One of them composed of barrier layers with PBAE and another with two types of barrier layers, PBAE and graphene oxide. The results indicate that one graphene oxide bilayer can delay the brimonidine release for more than 24 h. In vitro assays confirmed that the films have a cell viability of 100%.

Nanotechnology-Ocular Devices for Glaucoma Treatment: A Literature Review.

Nanotechnology enabled the development of materials and devices with great utility in different fields of medicine. By using engineered-based nano-devices and structures, human biological systems may be controlled and repaired at a molecular scale, ultimately leading to a biological benefit. In particular, in the field of glaucoma treatment, nanotechnology may, for example, enhance drug residence time on the ocular surface and ocular bioavailability, as well as improve surgical success by both optimizing postoperative scarring and providing a wider safety window. Further studies are still needed to entirely explain the pharmacodynamics of nanotechnology-based therapeutic approaches and prove their biological consequences in human eyes. This review aims to summarize the literature concerning the advances in nanotechnology, specifically regarding ocular devices applied to the treatment of glaucoma.

Influence of ionic interactions on the photoinduced birefringence of poly[1-[4-(3-carboxy-4 hydroxyphenylazo) benzene sulfonamido]-1,2-ethanediyl, sodium salt] films.

Electrostatic interactions govern most properties of polyelectrolyte films, as in the photoinduced birefringence of azo-containing polymers. In this paper we report a systematic investigation of optical storage characteristics of cast and layer-by-layer (LbL) films of poly[1 -[4-(3-carboxy-4 hydroxyphenylazo) benzene sulfonamido]-1,2-ethanediyl, sodium salt] (PAZO). Birefringence was photoinduced faster in PAZO cast films prepared at high pHs, with the characteristic writing times decreasing almost linearly with the pH in the range between 4 and 9. This was attributed to an increased free volume for the azochromophores with the enhanced electrostatic repulsion in PAZO charged to a greater extent. In contrast, in LbL films of PAZO alternated with poly(allylamine hydrochloride) (PAH), the electrostatic interactions between the oppositely charged polymers hampered photoisomerization and molecular rearrangement, thus leading to a slower writing kinetics for highly charged

Improving the Efficiency of Organic Solar Cells upon Addition of Polyvinylpyridine.

We report on the efficiency improvement of organic solar cells (OPVs) based on the low energy gap polyfluorene derivative, APFO-3, and the soluble C60 fullerene PCBM, upon addition of a residual amount of poly (4-vinylpyridine) (PVP). We find that the addition of 1% by weight of PVP with respect to the APFO-3 content leads to an increase of efficiency from 2.4% to 2.9%. Modifications in the phase separation details of the active layer were investigated as a possible origin of the efficiency increase. At high concentrations of PVP, the blend morphology is radically altered as observed by Atomic Force Microscopy. Although the use of low molecular weight additives is a routine method to improve OPVs efficiency, this report shows that inert polymers, in terms of optical and charge transport properties, may also improve the performance of polymer-based solar cells.

Long-term stability at high temperatures for birefringence in PAZO/PAH layer-by-layer films.

Optical memories with long-term stability at high temperatures have long been pursued in azopolymers with photoinduced birefringence. In this study, we show that the residual birefringence in layer-by-layer (LbL) films made with poly[1-[4-(3-carboxy-4 hydroxyphenylazo)benzene sulfonamido]-1,2-ethanediyl, sodium salt] (PAZO) alternated with poly(allylamine hydrochloride) (PAH) can be tuned by varying the extent of electrostatic interactions with film fabrication at different pHs for PAH. The dynamics of both writing and relaxation processes could be explained with a two-stage mechanism involving the orientation of the chromophores per se and the chain movement. Upon calculating the activation energies for these processes, we demonstrate semiquantitatively that reduced electrostatic interactions in films prepared at higher pH, for which PAH is less charged, are responsible for the longer stability at high temperatures. This is attributed to orientation of PAZO chromophores via cooperative aggregation, where the presence of counterions hindered relaxation.