Inflammatory bowel diseases (IBD) manifest from excessive intestinal inflammation. Local delivery of siRNA that targets these inflammatory cytokines would provide a novel treatment approach. Microencapsulated nanogels are designed and validated as platforms for oral delivery of siRNA targeting TNF-α, a common clinical target of IBD treatments. The preferred platform was designed to (i) protect siRNA-loaded nanogels from the harsh acidic environment of the upper GI tract and (ii) enzymatically degrade and release the nanogels once the carrier has reached the intestinal region. This platform consists of microgels composed of poly(methacrylic acid-co-N-vinyl-2-pyrrolidone) (P[MAA-co-NVP]) cross-linked with a trypsin-degradable peptide linker. The P(MAA-co-NVP) backbone is designed to collapse around and protect encapsulated nanogel from degradation at the low pH levels seen in the stomach (pH 2-4). At pH levels of 6-7.5, as typically observed in the intestine, the P(MAA-co-NVP) matrix swells, potentially facilitating diffusion of intestinal fluid and degradation of the matrix by intestinal enzymes such as trypsin, thus "freeing" the therapeutic nanogels for delivery and cellular uptake within the intestine. TNF-α siRNA-loaded nanogels released from this platform were capable of inducing potent knockdown of secreted TNF-α levels in murine macrophages, further validating the potential for this approach to be used for the treatment of IBD.
We report our studies to compare energy consumption of a CDI cell in constant voltage (CV) and constant current (CC) operations, with a focus on understanding the underlying physics of consumption patterns. The comparison is conducted under conditions that the CV and CC operations result in the same amounts of input charge and within identical charging phase durations. We present two electrical circuit models to simulate energy consumption in charging phase: one is a simple RC circuit model, and the other a transmission line circuit model. We built and tested a CDI cell to validate the transmission line model, and performed a series of experiments to compare CV versus CC operation under the condition of equal applied charge and charging duration. The experiments show that CC mode consumes energy at 33.8 kJ per mole of ions removed, which is only 28% of CV mode energy consumption (120.6 kJ/mole), but achieves similar level of salt removals. Together, the models and experiment support our major conclusion that CC is more energy efficient than CV for equal charge and charging duration. The models also suggest that the lower energy consumption of CC in charging is due to its lower resistive dissipation.
Critical to the success of three-dimensional (3D) printing of living materials with high performance is the development of new ink materials and 3D geometries that favor long-term cell functionality. Here we report the use of freezedried live cells as the solid filler to enable a new living material system for direct ink writing of catalytically active microorganisms with tunable densities and various self-supporting porous 3D geometries. Baker's yeast was used as an exemplary live whole-cell biocatalyst, and the printed structures displayed high resolution, large scale, high catalytic activity and long-term viability. An unprecedented high cell loading was achieved, and cell inks showed unique thixotropic behavior. In the presence of glucose, printed bioscaffolds exhibited increased ethanol production compared to bulk counterparts due largely to improved mass transfer through engineered porous structures. The new living materials developed in this work could serve as a versatile platform for process intensification of an array of bioconversion processes utilizing diverse microbial biocatalysts for production of high-value products or bioremediation applications.
Here we detail a previously unappreciated loss mechanism inherent to capacitive deionization (CDI) cycling operation that has a substantial role determining performance. This mechanism reflects the fact that desalinated water inside a cell is partially lost to re-salination if desorption is carried out immediately after adsorption. We describe such effects by a parameter called the flow efficiency, and show that this efficiency is distinct from and yet multiplicative with other highly-studied adsorption efficiencies. Flow losses can be minimized by flowing more feed solution through the cell during desalination; however, this also results in less effluent concentration reduction. While the rationale outlined here is applicable to all CDI cell architectures that rely on cycling, we validate our model with a flow-through electrode CDI device operated in constant-current mode. We find excellent agreement between flow efficiency model predictions and experimental results, thus giving researchers simple equations by which they can estimate this distinct loss process for their operation.
Multi-responsive hydrogels, or ‘intelligent’ hydrogels that respond to more than one environmental stimulus, have demonstrated great utility as a regenerative biomaterial in recent years. They are structured biocompatible materials that provide specific and distinct responses to varied physiological or externally applied stimuli. As evidenced by a burgeoning number of investigators, multi-responsive hydrogels are endowed with tunable, controllable and even biomimetic behavior well-suited for drug delivery and tissue engineering or regenerative growth applications. This article encompasses recent developments and challenges regarding supramolecular, layer-by-layer assembled and covalently cross-linked multi-responsive hydrogel networks and their application to drug delivery and tissue engineering.
An industrial process for the selective activation of methane under mild conditions would be highly valuable for controlling emissions to the environment and for utilizing vast new sources of natural gas. The only selective catalysts for methane activation and conversion to methanol under mild conditions are methane monooxygenases (MMOs) found in methanotrophic bacteria; however, these enzymes are not amenable to standard enzyme immobilization approaches. Using particulate methane monooxygenase (pMMO), we create a biocatalytic polymer material that converts methane to methanol. We demonstrate embedding the material within a silicone lattice to create mechanically robust, gas-permeable membranes, and direct printing of micron-scale structures with controlled geometry. Remarkably, the enzymes retain up to 100% activity in the polymer construct. The printed enzyme-embedded polymer motif is highly flexible for future development and should be useful in a wide range of applications, especially those involving gas–liquid reactions.
Multiresponsive poly(methacrylic acid-co-N-vinylpyrrolidone) hydrogels were synthesized with biodegradable oligopeptide crosslinks. The oligopeptide crosslinks were incorporated using EDC-NHS zero-length links between the carboxylic acid groups of the polymer and free primary amines on the peptide. The reaction of the peptide was confirmed by primary amine assay and IR spectroscopy. The microgels exhibited pH-responsive swelling as well as enzyme-catalyzed degradation targeted by trypsin present in the small intestine, as demonstrated upon incubation with gastrointestinal fluids from rats. Relative turbidity was used to evaluate enzyme-catalyzed degradation as a function of time, and initial trypsin concentration controlled both the degradation mechanism as well as the extent of degradation. Trypsin activity was effectively extinguished by incubation at 70 °C, and both the microgels and degradation products posed no cytotoxic effect toward two different cell lines. The microgels demonstrated pH-dependent loading of the protein insulin for oral delivery to the small intestine.
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