Fluorine Effect in the Gelation Ability of Low Molecular Weight Gelators

The three gelators presented in this work (Boc-D-Phe-L-Oxd-OH F0, Boc-D-F1Phe-L-Oxd-OH F1 and Boc-D-F2Phe-L-Oxd-OH F2) share the same scaffold and differ in the number of fluorine atoms linked to the aromatic ring of phenylalanine. They have been applied to the preparation of gels in 0.5% or 1.0% w/v concentration, using three methodologies: solvent switch, pH change and calcium ions addition. The general trend is an increased tendency to form structured materials from F0 to F1 and F2. This property ends up in the formation of stronger materials when fluorine atoms are present. Some samples, generally formed by F1 or F2 in 0.5% w/v concentration, show high transparency but low mechanical properties. Two gels, both containing fluorine atoms, show increased stiffness coupled with high transparency. The biocompatibility of the gelators was assessed exposing them to fibroblast cells and demonstrated that F1 and F2 are not toxic to cells even in high concentration, while F0 is not toxic to cells only in a low concentration. In conclusion, the presence of even only one fluorine atom improves all the gelators properties: the gelation ability of the compound, the rheological properties and the transparency of the final materials and the gelator biocompatibility

Retinoic acid/calcite micro-carriers inserted in fibrin scaffolds modulate neuronal cell differentiation

The controlled release of cell differentiating agents is crucial in many aspects of regenerative medicine. Here we propose the use of hybrid calcite single crystals as micro-carriers for the controlled and localized release of retinoic acid, which is entrapped within the crystalline lattice. The release of retinoic acid occurs only in the proximity of stem cells, upon dissolution of the calcite hybrid crystals that are dispersed in the fibrin scaffold. These hybrid crystals provide a sustained dosage of the entrapped agent. The environment provided by this composite scaffold enables differentiation towards neuronal cells that form a three-dimensional neuronal network

Green Biocompatible Method for the Synthesis of Collagen/Chitin Composites to Study Their Composition and Assembly Influence on Fibroblasts Growth

A green biocompatible route for the deposition and simultaneous assembly, by pH increment, of collagen/chitin composites was proposed. Both assembled and unassembled samples with different collagen/chitin ratios were synthesized, maintaining the β-chitin polymorph. The first set showed a microfibrous organization with compositional submicron homogeneity. The second set presented a nanohomogeneous composition based on collagen nanoaggregates and chitin nanofibrils. The sets were tested as scaffolds for fibroblast growth (NIH-3T3) to study the influence of composition and assembly. In the unassembled scaffolds, the positive influence of collagen on cell growth mostly worn out in 48 h, while the addition of chitin enhanced this effect for over 72 h. The assembled samples showed higher viability at 24 h but a less positive effect on viability along the time. This work highlighted critical aspects of the influence that composition and assembly has on fibroblast growth, a knowledge worth exploiting in scaffold design and preparation

Organic electrochemical transistors (OECTs) for smart monitoring of cell stress condition in leaky-barrier cell lines

Semiconducting polymers are very promising materials for biomedical application, thanks to the ability to conduct both ions and electrons, their biocompatibility and their flexible and soft mechanical properties. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has high conductivity, electrochemical and thermal stability in aqueous environment and low oxidation potential that renders it suitable as smart nano-interface with biological elements and environment. In our work, we present PEDOT:PSS-based Organic Electrochemical Transistors (OECTs) for the electrical continuous monitoring of tissue culture viability, growth and stress response induce by drug treatment, providing an alternative and real-time way to standard optical evaluation techniques, which often require complex instrumentation and laboratory protocols. In OECTs, the electronic current flowing in the conducting polymer channel is modulated by the ionic current crossing the interface with an electrolyte solution (cell culture medium). The presence of a cell monolayer, directly grown on the semiconducting channels and gates of our devices, slow down the ions flowing in the conducting polymer, thus giving an electronic readout of the layer integrity and health. Moreover, the transistor configuration enhances the sensitivity due to amplification of the ionic current. Finally, changing the dimensions of the device and switching between its two configurations, renders it suitable for different kind of cells, allowing even the study of leaky-barrier or non-barrier cell lines. We demonstrated that our devices provide a simple, low-cost and dynamic method to monitor cell viability and reactions to toxic agents of CaCo-2 and NIH-3T3 cell lines, paving the way for high throughput and low-cost screening of drug discovery or toxicology

Tuning mechanical properties of pseudopeptide supramolecular hydrogels by graphene doping

Supramolecular hydrogels, obtained from small organic molecules, may be advantageous over polymeric ones for several applications, because these materials have some peculiar properties that differentiate them from the traditional polymeric hydrogels, such as elasticity, thixotropy, self-healing propensity, and biocompatibility. We report here the preparation of strong supramolecular pseudopeptide-based hydrogels that owe their strength to the introduction of graphene in the gelling mixture. These materials proved to be strong, stable, thermoreversible and elastic. The concentration of the gelator, the degree of graphene doping, and the nature of the trigger are crucial to get hydrogels with the desired properties, where a high storage modulus coexists with a good thixotropic behavior. Finally, NIH-3T3 cells were used to evaluate the cell response to the presence of the most promising hydrogels. The hydrogels biocompatibility remains good, if a small degree of graphene doping is introduced

Organic Ultra-Thin Film Transistor with Liquid Gate for Extracellular Stimulation and Recording of Electric Activity of Stem Cell-Derived Neuronal Networks

Electronic transducers of neuronal cellular activity are important devices in neuroscience and neurology. Organic field-effect transistors (OFETs) offer tailored surface chemistry, mechanical flexibility, and high sensitivity to electrostatic potential changes at device interfaces. These properties make them attractive for interfacing electronics with neural cells and performing extracellular recordings and stimulation of neuronal network activity. In this work we operate pentacene ultra-thin film (9 nm thick) transistors with a liquid gate both as transducers and electrical stimulators of neuronal network activity. These devices are highly sensitive to small potential changes in cell medium and exhibit sufficient stability under standard cell culture conditions for nine days. We show that murine neural stem cells can be adhered on top of functional devices without the need for an additional layer of cell-adhesive molecules, and then differentiated into neuronal networks. OFET response is monitored during the different phases of the neuronal differentiation process up to nine days. Only when stem cells are differentiated into neurons, it is possible to measure electrical signals in the OFET current following the stimulation. Due to the large sensing area of our device, which accommodates from hundreds to thousands of interconnected neurons, the OFET electrical signals arise from the collective electrophysiological response of the neuronal population. The maximum extracellular potential change in the cleft region adjacent to the transistor surface amounts to 350 mu V. This demonstrates that pentacene ultra-thin film OFETs enable good cellular adhesion and efficient coupling of the ionic currents at the biological-organic semiconductor interface with the OFET current

Selective Growth of α-Sexithiophene by Using Silicon Oxides Patterns

A process for fabricating ordered organic films on large area is presented. The process allows growing sexithiophene ultra-thin films at precise locations on patterned Si/SiOx substrates by driving the orientation of growth. This process combines the parallel local anodic oxidation of Si/SiOx substrates with the selective arrangement of molecular ultra-thin film. The former is used to fabricate silicon oxide arrays of parallel lines of 400 nm in width over an area of 1 cm(2). Selective growth arises from the interplay between kinetic growth parameters and preferential interactions with the patterned surface. The result is an ultra-thin film of organic molecules that is conformal to the features of the fabricated motives