Piotr J. Glazer

Role of pH gradients in the actuation of electro-responsive polyelectrolyte gels

Polyelectrolyte gels are able to mimic artificial muscles, swelling, shrinking or bending in response to environmental stimuli. Mechanical response is also observed in the presence of an electric field, in which case electrical energy is directly converted into mechanical energy. Although several mechanisms have been proposed to describe electro-actuating in polyelectrolyte gels, no consensus yet exists on which mechanisms are responsible for this phenomenon. Here we use a universal pH indicator to investigate the role of localized pH changes in the gel during bending electro-actuation. We show that, when the gel is not in contact with the electrodes, a pH wave propagating from the electrodes is not the factor that triggers or determines the amplitude of electro-actuation. We also show that, surprisingly, the direction of actuation depends on the salt concentration in the surrounding electrolyte. The polarity of actuation is consistent with models based on dynamic enrichment and depletion of electrolyte for low salt conditions, but reverses at physiological salt concentrations. This suggests that not all experimental observations can be described in terms of a single simple model, and that further theoretical work is needed in the case of physiological salt conditions

Nonendocytic delivery of lipoplex nanoparticles into living cells using nanochannel electroporation.

The delivery of biomolecules, including siRNAs (≈21 bp) and large plasmids (≈10 kbp), into living cells holds a great promise for therapeutic and research applications. Lipoplex nanoparticles are popular nanocarriers for gene delivery. In conventional transfection methods, the cellular uptake of lipoplex nanoparticels occurs through the endocytosis process. The entrapment of lipoplex nanoparticles into endocytic vesicle is a major barrier in achieving efficient gene silencing and expression. Here, a novel nanochannel electroporation (NEP) method is employed to facilitate the cellular uptake and release of siRNAs/DNAs from lipoplexes. First, it is demonstrated that in a NEP device, lipoplex nanoparticles can be injected directly into the cell cytoplasm within several seconds. Specifically, it is found that lipoplexes containing MCL-1 siRNA delivered by NEP can more efficiently down-regulate the expression of MCL-1 mRNA in A549 cancer cells than conventional transfection. Quantum dot-mediated Förster resonance energy transfer (QD-FRET) reveals that lipoplexes delivered via NEP can directly release siRNA in the cytoplasm without going through the endocytosis route, which unravels the responsible mechanism for efficient gene delivery. Furthermore, the advantage of combining NEP with lipoplex nanoparticles by the successful delivery of large plasmids (pCAG2LMKOSimO, 13 kbp) into CHO cells is demonstrated.

Generating Aligned Micellar Nanowire Arrays by Dewetting of Micropatterned Surfaces

Macroscopic fabrication of one-dimensional (1D) nanostructures, including nanowires, nanofi bers, nanorods, and nanotubes, with well-ordered arrangement is of great interest for physics, chemistry, and biology not only due to the fundamental questions they raise but also their technological implication in mesoscopic functional devices. [ 1–3 ] Exhibiting high aspect ratios (length to diameter ratio of 100 or more), quantized conductance, and size-dependent emission in sub100 nm regime, 1D nanowires are promising for construction of nanoscale transistors, sensors and optoelectronics. [ 4–10 ]

Electro-actuation of biocompatible Pluronic/methacrylic acid hydrogel in blood-plasma and in blood-mimicking buffers

The electro-responsiveness in blood plasma and in blood mimicking fluids of methacrylic acid modified Pluronic (P127) hydrogel is investigated. It is observed that the hydrogels response to an applied potential, in all buffer solutions, is very high, and comparable in amplitude and time response to classic polyelectrolyte gels. The highest actuation amplitude is achieved in PBS, which is directly related to the largest current value obtained for that buffer. The electro-actuation achieved in blood plasma is comparable to that in KREBS and KCl buffers. The good performance in blood plasma is attributed to the low protein adhesion to hydrogel surface. Preliminary biocompatibility studies demonstrate that the investigated hydrogel can be considered biocompatible.

A facile approach for the fabrication of 2D supermicelle networks

A novel and facile approach to fabricating well-organized macroscopic 2D networks of cylindrical micelles is reported, based on transfer printing and thermal welding of aligned supramolecular micelles of block copolymers. This versatile approach provides a new strategy for fabricating functional 2D superstructures with a higher level of order.

A Cardiovascular Occlusion Method Based on the Use of a Smart Hydrogel

Smart hydrogels for biomedical applications are highly researched materials. However, integrating them into a device for implantation is difficult. This paper investigates an integrated delivery device designed to deliver an electro-responsive hydrogel to a target location inside a blood vessel with the purpose of creating an occlusion. The paper describes the synthesis and characterization of a Pluronic/methacrylic acid sodium salt electro-responsive hydrogel. Application of an electrical bias decelerates the expansion of the hydrogel. An integrated delivery system was manufactured to deliver the hydrogel to the target location in the body. Ex vivo and in vivo experiments in the carotid artery of sheep were used to validate the concept. The hydrogel was able to completely occlude the blood vessel reducing the blood flow from 245 to 0 ml/min after implantation. Ex vivo experiments showed that the hydrogel was able to withstand physiological blood pressures of > 270 mm·Hg without dislodgement. The results showed that the electro-responsive hydrogel used in this paper can be used to create a long-term occlusion in a blood vessel without any apparent side effects. The delivery system developed is a promising device for the delivery of electro-responsive hydrogels.

Two Robust Strategies toward Hydrogels from Quenched Block Copolymer Nanofibrillar Micelles

While the formation of (tri)block copolymer hydrogels has been extensively investigated, such studies mostly focused on equilibrium self-assembling whereas the use of preformed structures as building blocks such as out of equilibrium, quenched, nanofibrillar micelles is still a challenge. Here, we demonstrate that quenched, ultralong polystyrene-b-poly(ethylene oxide) (PS-b-PEO) micelles can be used as robust precursors of hydrogels. Two cross-linking strategies, (i) thermal fusion of micellar cores and (ii) chemical cross-linking of preformed micellar coronas were studied. The gelation process and the structure of the micellar networks were investigated by in situ rheological measurements, confocal microscopy and transmission electron microscopy. Direct observation of core fusion of preformed quenched micelles is provided validating this method as a robust gelation route. Using time sweep rheological experiments, it was found for both cross-linking methods that these 3D “mikado” gels are formed in three different stages, containing (1) initiation, (2) transition (growth), and (3) stabilization regimes.

Affordable techniques for fabricating large array of functional nanowires: From DNA to micellar systems.

Large arrays of aligned DNA and polymeric nanowires ranging from 20 to 100 nm in diameter are fabricated by de-wetting of patterned surfaces. Compared to other nanofabrication techniques, our approach is robust, fast and low cost. In addition, arrays of functionalized nanowires for bio/chemical applications can be simply produced at large scale.