Electroactive 4D Porous Scaffold Based on Conducting Polymer as a Responsive and Dynamic In Vitro Cell Culture Platform.

In vivo, cells reside in a 3D porous and dynamic microenvironment. It provides biochemical and biophysical cues that regulate cell behavior in physiological and pathological processes. In the context of fundamental cell biology research, tissue engineering, and cell-based drug screening systems, a challenge is to develop relevant in vitro models that could integrate the dynamic properties of the cell microenvironment. Taking advantage of the promising high internal phase emulsion templating, we here designed a polyHIPE scaffold with a wide interconnected porosity and functionalized its internal 3D surface with a thin layer of electroactive conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) to turn it into a 4D electroresponsive scaffold. The resulting scaffold was cytocompatible with fibroblasts, supported cellular infiltration, and hosted cells, which display a 3D spreading morphology. It demonstrated robust actuation in ion- and protein-rich complex culture media, and its electroresponsiveness was not altered by fibroblast colonization. Thanks to customized electrochemical stimulation setups, the electromechanical response of the polyHIPE/PEDOT scaffolds was characterized in situ under a confocal microscope and showed 10% reversible volume variations. Finally, the setups were used to monitor in real time and in situ fibroblasts cultured into the polyHIPE/PEDOT scaffold during several cycles of electromechanical stimuli. Thus, we demonstrated the proof of concept of this tunable scaffold as a tool for future 4D cell culture and mechanobiology studies.

Electroactive Bi-Functional Liquid Crystal Elastomer Actuators.

Liquid crystal elastomers (LCEs) with promising applications in the field of actuators and soft robotics are reported. However, most of them are activated by external heating or light illumination. The examples of electroactive LCEs are still limited; moreover, they are monofunctional with one type of deformation (bending or contraction). Here, the study reports on trilayer electroactive LCE (eLCE) by intimate combination of LCE and ionic electroactive polymer device (i-EAD). This eLCE is bi-functional and can perform either bending or contractile deformations by the control of the low-voltage stimulation. By applying a voltage of ±2 V at 0.1 Hz, the redox behavior and associated ionic motion provide a bending strain difference of 0.80%. Besides, by applying a voltage of ±6 V at 10 Hz, the ionic current-induced Joule heating triggers the muscle-like linear contraction with 20% strain for eLCE without load. With load, eLCE can lift a weight of 270 times of eLCE-actuator weight, while keeping 20% strain and affording 5.38 kJ·m-3 work capacity. This approach of combining two smart polymer technologies (LCE and i-EAD) in a single device is promising for the development of smart materials with multiple degrees of freedom in soft robotics, electronic devices, and sensors.

Vitrimer ionogels towards sustainable solid-state electrolytes.

The growing demand for flexible, stretchable, and wearable devices has boosted the development of ionogels used as polymer electrolytes. Developing healable ionogels based on vitrimer chemistry is a promising approach to improve their lifetimes as these materials are usually subjected to repeated deformation during functioning and are susceptible to damage. In this work, we reported in the first place the preparation of polythioether vitrimer networks based on the not extensively studied associative S-transalkylation exchange reaction using thiol-ene Michael addition. Thanks to the exchange reaction of sulfonium salts with thioether nucleophiles, these materials demonstrated vitrimer properties such as healing and stress relaxation. The fabrication of dynamic polythioether ionogels was then demonstrated by loading 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide or 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMIM triflate) within the polymer network. The resulting ionogels exhibited Young's modulus of 0.9 MPa and ionic conductivities in the order of 10-4 S cm-1 at room temperature. It has been found that adding ionic liquids (ILs) changes the dynamic properties of the systems, most likely due to a dilution effect of the dynamic functions by the IL but also due to a screening effect of the alkyl sulfonium OBrs-couple by the ions of the IL itself. To the best of our knowledge, these are the first vitrimer ionogels based on an S-transalkylation exchange reaction. While the addition of ILs resulted in less efficient dynamic healing at a given temperature, these ionogels can provide materials with more dimensional stability at application temperatures and can potentially pave the way for the development of tunable dynamic ionogels for flexible electronics with a longer lifespan.

Healable Ionoelastomer Designed from Polymeric Ionic Liquid and Vitrimer Chemistry.

The growing demand for all-solid flexible, stretchable, and wearable devices has boosted the need for liquid-free and stretchable ionoelastomers. These ionic conducting materials are subjected to repeated deformations during functioning, making them susceptible to damage. Thus, imparting cross-linked materials with healing ability seems particularly promising to improve their durability. Here, a polymeric ionic liquid (PIL) bearing allyl functional groups was synthesized based on the quaternization of N-allylimidazole with a copolymer rubber of poly(epichlorohydrin) and poly(ethylene oxide) (PEO). The resulting PIL was then cross-linked with dynamic boronic ester cross-linkers 2,2'-(1,4-Phenylene)-bis[4-mercaptan-1,3,2-dioxaborolane] (BDB) through thiol-ene "click" photoaddition. PEO dangling chains were additionally introduced for acting as free volume enhancers. The properties of the resulting all-solid PIL networks were investigated by tuning dynamic cross-linkers and dangling chain contents. Adjusting the cross-linker and dangling chain quantities yielded soft (0.2 MPa), stretchable (300%), and highly conducting ionoelastomers (1.6 × 10-5 S·cm-1 at 30 °C). The associative exchange reaction between BDB endowed these materials with vitrimer properties such as healing and recyclability. The recycled materials were able to retain their original mechanical properties and ionic conductivity. These healable PIL networks display a great potential for applications requiring solid electrolytes with high ionic conductivity, healing ability, and reprocessability.

Photopolymerizable Ionogel with Healable Properties Based on Dioxaborolane Vitrimer Chemistry.

Ionogels are solid polymer gel networks loaded with ionic liquid (IL) percolating throughout each other, giving rise to ionically conducting solid electrolytes. They combine the mechanical properties of polymer networks with the ionic conductivity, non-volatility, and non-flammability of ILs. In the frame of their applications in electrochemical-based flexible electronics, ionogels are usually subjected to repeated deformation, making them susceptible to damage. It appears critical to devise a simple and effective strategy to improve their durability and lifespan by imparting them with healing ability through vitrimer chemistry. In this work, we report the original in situ synthesis of polythioether (PTE)-based vitrimer ionogels using fast photopolymerization through thiol-acrylate Michael addition. PTE-based vitrimer was prepared with a constant amount of the trithiol crosslinker and varied proportions of static dithiol spacers and dynamic chain extender BDB containing dynamic exchangeable boronic ester groups. The dynamic ionogels were prepared using 50 wt% of either 1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide or 1-Ethyl-3-methylimidazolium trifluoromethanesulfonate, both of which were selected for their high ionic conductivity. They are completely amorphous (Tg below -30 °C), suggesting they can be used at low temperatures. They are stretchable with an elongation at break around 60%, soft with Young's modulus between 0.4 and 0.6 MPa, and they have high ionic conductivities for solid state electrolytes in the order of 10-4 S·cm-1 at room temperature. They display dynamic properties typical of the vitrimer network, such as stress relaxation and healing, retained despite the large quantity of IL. The design concept illustrated in this work further enlarges the library of vitrimer ionogels and could potentially open a new path for the development of more sustainable, flexible electrochemical-based electronics with extended service life through repair or reprocessing.

Fabrication of bicontinuous double networks as thermal and pH stimuli responsive drug carriers for on-demand release.

The fabrication, via a two steps approach, of a novel bicontinuous Double Network (BCDN) material is reported. We first use a bicontinuous emulsion as template to obtain a poly(butyl acrylate) (PBA) and poly(acrylic acid) (PAA) bicontinuous amphiphilic material. The material is then swollen with the precursor of a second hydrophilic polymer (PNIPAM, poly(N-isopropylacrylamide)). After polymerization of these precursors, the two responsive polymers, PNIPAM and PAA, form a double-network within a bicontinuous templated material, i.e. a bicontinuous double network (BCDN) material. The advantages of using such unique and complex double network architecture are manifold. PBA increases the mechanical properties of the hydrogel all together with the hydrophilic double network that also decouples the pH and temperature responsiveness. Among different possible applications, we tested this responsive hydrogels for its biomedical application. It can be used as pH and temperature sensitive devices for on-demand drug delivery. In addition, the release of a drug confined in the amphiphilic bicontinuous structure follows different kinetics profiles, depending on pH and temperature. This last result indicates that it is possible to control and regulate the release of an encapsulated drug according to the fluctuations of physiological conditions.

Multi-stimuli responsive nanogel/hydrogel nanocomposites based on κ-carrageenan for prolonged release of levodopa as model drug.

This study describes the development of a novel biocompatible nanogel/hydrogel nanocomposite system for long-term delivery of bioactive molecules. To this aim, the nanogels were synthesized via radical polymerization of poly(N-isopropylacrylamide). The nanogels were introduced during the formation of a hydrogel network to produce nanogel/hydrogel soft nanocomposites, while the biocompatible hydrogel was based on poly (acrylic acid) grafted onto κ-carrageenan polysaccharide with entrapped magnetic iron oxide nanoparticles as crosslinker. In these systems, by using stimuli-responsive functional polymers in both gels (nanogels and hydrogels), pH, thermal and magnetic-responsive properties can be brought to final soft nanocomposites. The obtained soft nanocomposite was characterized by Fourier transform infrared spectrum (FT-IR), thermogravimetric (TG) analysis, and scanning electron microscopy (SEM). This biopolymer based nanogel/hydrogel used as a prolonged releasing drug carrier for levodopa (L-DOPA) as a main drug for treating Parkinson's symptoms. The in vitro release of L-DOPA was investigated at different pHs. pH-dependent release of the active drug can be sustained for >11 days from this soft nanocomposite. The results demonstrated a sustained release model that can be extended for other drugs.

Nanostructured Thermal Responsive Materials Synthesized by Soft Templating.

We capitalized herein the inherent tortuosity of bicontinuous microemulsion to conceive nanostructured drug-delivery devices. First, we show that it is possible to synthesize bicontinuous materials with continuous hydrophilic domains of the poly(N-isopropylacrylamide) (PNIPAM) network entangled with continuous hydrophobic polymer domains, with dual-phase continuity being imposed by the bicontinuous microemulsions used as a soft template. Particular attention is paid to the microemulsion formulations using a surfmer to preserve the one-to-one replication of the bicontinuous nanostructure after polymerization. These materials keep a volume phase transition with temperature that allows considering them as drug carriers for controlled release. PNIPAM, which plays the role of the active ingredient reservoir, is confined in the bicontinuous structure. As expected, the PNIPAM enclosure limits the surface area in contact with the releasing aqueous solution and thus slows down the desorption of aspirin, which is used as a model drug. The hydrophobic polymers play the role of in situ-created transport barriers without hindering it as all the loaded aspirin in this bicontinuous structure still remains available.

Nanostructure Changes upon Polymerization of Aqueous and Organic Phases in Organized Mixtures.

The nanostructure of a microemulsion can be strongly affected by the liquid-to-solid transition during polymerization. Here, we examined the evolution of nanostructures of different ternary mixtures, including two microemulsions and a single lamellar phase that upon polymerization are quantitatively studied by SAXS/WAXS and DSC experiments systematically performed before and after the polymerization of both aqueous and organic phases. Samples are mixtures of the poly(2-acrylamido-2-methylpropanesulfonic acid) network as the aqueous phase and poly(hexyl methacrylate) as the organic phase stabilized by Brij35 surfactant. Upon polymerization, the surfactant is excluded from the water/oil interface and crystallizes, strongly changing the nanostructure of samples where it is the main component. In samples where the aqueous phase is the main component, only a few changes in structure are observed upon polymerization. This study demonstrates quantitatively the possibility to preserve nanostructures during polymerization, thus inducing a templating effect.

Self-supported fibrin-polyvinyl alcohol interpenetrating polymer networks: an easily handled and rehydratable biomaterial.

A fibrin hydrogel at physiological concentration (5 mg/mL) was associated with polyvinyl alcohol (PVA) inside an interpenetrating polymer networks (IPN) architecture. Previously, PVA has been modified with methacrylate functions in order to cross-link it by free-radical polymerization. The fibrin network was synthesized by the enzymatic hydrolysis of fibrinogen by thrombin. The resulting self-supported materials simultaneously exhibit the properties of the fibrin hydrogel and those of the synthetic polymer network. Their storage modulus is 50-fold higher than that of the fibrin hydrogel and they are completely rehydratable. These materials are noncytotoxic toward human fibroblast and the fibrin present on the surface of PVAm-based IPNs favors cell development.

Labeling of fibronectin by fluorescent and paramagnetic nanoprobes for exploring the extracellular matrix: bioconjugate synthesis optimization and biochemical characterization.

In this study, fibronectin-nanoparticles bioconjugates are developed and characterized. Multilabeled nanoparticles are composed of a core of the rare-earth oxide Gd(2)O(3):Tb(3+), capped with a set of Rhodamine B isothiocyanate encapsulated in a silica matrix and functionalized by a carboxylated polyethylene glycol shell. These nanoparticles are stabilized in aqueous solution and are found to contain about 400 carboxyl groups on their surface. Nanoparticle bioconjugation with highly purified human plasma fibronectin (Fn) is mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, resulting in an amide linkage between the carboxylic acid-terminated surface of the nanoparticle and the primary amine of Fn. The bioconjugation temperature and pH are optimized. The Local structure and global conformation of fibronectin-nanoparticle bioconjugates (FnNP*) are studied by fluorescence spectroscopy and enzymatic sites accessibility. Protein biochemical functionalities are globally conserved, and the protein is actually labeled. Elaboration of such complexes provides a promising bimodal contrasting agent for in vivo imaging.

Lanthanide-containing polymer nanoparticles for biological tagging applications: nonspecific endocytosis and cell adhesion.

We describe the synthesis and characterization of element-encoded polystyrene nanoparticles with diameters on the order of 100 nm and a narrow size distribution. Individual particles contain ca. 10(3) chelated lanthanide ions, of either a single element or a mixture of elements. These particles were effectively internalized by nonspecific endocytosis into three cell lines associated with human leukemia. Using an assay based upon ICP-MS detection, we could monitor quantitatively cell adhesion induced by cell differentiation of THP-1 cells in response to phorbol ester stimulation (PMA) in single cell type or mixed cultures.