Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD.

Alveolar epithelial type II (AEC2) cells strictly regulate lipid metabolism to maintain surfactant synthesis. Loss of AEC2 cell function and surfactant production are implicated in the pathogenesis of the smoking-related lung disease chronic obstructive pulmonary disease (COPD). Whether smoking alters lipid synthesis in AEC2 cells and whether altering lipid metabolism in AEC2 cells contributes to COPD development are unclear. In this study, high-throughput lipidomic analysis revealed increased lipid biosynthesis in AEC2 cells isolated from mice chronically exposed to cigarette smoke (CS). Mice with a targeted deletion of the de novo lipogenesis enzyme, fatty acid synthase (FASN), in AEC2 cells (FasniΔAEC2) exposed to CS exhibited higher bronchoalveolar lavage fluid (BALF) neutrophils, higher BALF protein, and more severe airspace enlargement. FasniΔAEC2 mice exposed to CS had lower levels of key surfactant phospholipids but higher levels of BALF ether phospholipids, sphingomyelins, and polyunsaturated fatty acid-containing phospholipids, as well as increased BALF surface tension. FasniΔAEC2 mice exposed to CS also had higher levels of protective ferroptosis markers in the lung. These data suggest that AEC2 cell FASN modulates the response of the lung to smoke by regulating the composition of the surfactant phospholipidome.

Fiber Reinforced Cartilage ECM Functionalized Bioinks for Functional Cartilage Tissue Engineering.

Focal articular cartilage (AC) defects, if left untreated, can lead to debilitating diseases such as osteoarthritis. While several tissue engineering strategies have been developed to promote cartilage regeneration, it is still challenging to generate functional AC capable of sustaining high load-bearing environments. Here, a new class of cartilage extracellular matrix (cECM)-functionalized alginate bioink is developed for the bioprinting of cartilaginous tissues. The bioinks are 3D-printable, support mesenchymal stem cell (MSC) viability postprinting and robust chondrogenesis in vitro, with the highest levels of COLLII and ACAN expression observed in bioinks containing the highest concentration of cECM. Enhanced chondrogenesis in cECM-functionalized bioinks is also associated with progression along an endochondral-like pathway, as evident by increases in RUNX2 expression and calcium deposition in vitro. The bioinks loaded with MSCs and TGF-ß3 are also found capable of supporting robust chondrogenesis, opening the possibility of using such bioinks for direct "print-and-implant" cartilage repair strategies. Finally, it is demonstrated that networks of 3D-printed polycaprolactone fibers with compressive modulus comparable to native AC can be used to mechanically reinforce these bioinks, with no loss in cell viability. It is envisioned that combinations of such biomaterials can be used in multiple-tool biofabrication strategies for the bioprinting of biomimetic cartilaginous implants.

Effect of tetraalkylammonium cations on gas coalescence at a hydrogen-evolving microelectrode.

Hydrogen gas evolution at the surface of a microelectrode may result in periodic release of single bubbles larger than the electrode diameter. Bubbles often grow by incorporating smaller bubbles that coalesce with them. To explore the coalescence, we investigate how a series of six tetralkylammonium cations (TXA(+)), where the number of carbons on the alkyl chain varies from 1 to 6, affects the oscillatory behavior of the gas-evolving microcathode. Different concentrations of TXA(+) bromide salts ranging from a few micromolar up to 1 M were added in the acid electrolyte. The frequency of bubble release and the transition from periodic to aperiodic release are related to the inhibition of bubble coalescence and gas streaming. The concentration range where this transition occurs depends strongly on the cation hydrophobicity and it ranges from very small values for the hydrophobic cations to over 1 M for the most hydrophilic one. For some of the TXA(+) cations, the transition shows a smooth increase in release frequency before switching completely to bubble-stream behavior, while for others the transition is abrupt. A smooth increase in the gas oscillator frequency with concentration indicates that the adsorption of TXA(+) cations on the bubble surface is mass transport-limited. The inhibition of bubble coalescence by the smallest cations is electrochemically driven, facilitated by specific interactions established between the ions and the electrode surface.

Bubble formation at a gas-evolving microelectrode.

The electrolytic production of gas bubbles involves three steps--nucleation, growth, and detachment. Here the growth of hydrogen bubbles and their detachment from a platinum microelectrode of diameter 125 µm are studied using high-speed photography and overpotential frequency spectrum (noise) analysis. The periodic release of large <800 µm bubbles--gas oscillator behavior--was often observed, with a corresponding periodic oscillation of the overpotential which is reflected as a main peak and a series of harmonics in the power spectral density. The release frequency is inversely correlated with the bubble size and hydrogen production rate. When the coalescence of bubbles at the electrode surface is inhibited, either chemically with a surfactant or ethylene glycol or hydrodynamically by magnetically induced convection, swarms of small ∼50 µm bubbles are released in an aperiodic stream. The abrupt transition from periodic to aperiodic release occurs when the surface tension falls below 70 mN m(-1). Hydrogen bubble growth is also studied on a transparent platinum thin-film electrode, where the bubble coalescence can be observed directly. It leaves sessile droplets of electrolyte within the footprint of the growing bubble, showing that the growth involves scavenging smaller bubbles from solution due to hydrogen generated directly at the electrode. A possible role of nanobubbles in the lift-off process is discussed.