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    Uncertainty Quantification and Sensitivity Analysis for the Electrical Impedance Spectroscopy of Changes to Intercellular Junctions Induced by Cold Atmospheric Plasma
    (Basel : MDPI, 2022) Zhuang, Jie; Zhu, Cheng; Han, Rui; Steuer, Anna; Kolb, Juergen F.; Shi, Fukun
    The influence of pertinent parameters of a Cole-Cole model in the impedimetric assessment of cell-monolayers was investigated with respect to the significance of their individual contribution. The analysis enables conclusions on characteristics, such as intercellular junctions. Especially cold atmospheric plasma (CAP) has been proven to influence intercellular junctions which may become a key factor in CAP-related biological effects. Therefore, the response of rat liver epithelial cells (WB-F344) and their malignant counterpart (WB-ras) was studied by electrical impedance spectroscopy (EIS). Cell monolayers before and after CAP treatment were analyzed. An uncertainty quantification (UQ) of Cole parameters revealed the frequency cut-off point between low and high frequency resistances. A sensitivity analysis (SA) showed that the Cole parameters, R0 and α were the most sensitive, while Rinf and τ were the least sensitive. The temporal development of major Cole parameters indicates that CAP induced reversible changes in intercellular junctions, but not significant changes in membrane permeability. Sustained changes of τ suggested that long-lived ROS, such as H2O2, might play an important role. The proposed analysis confirms that an inherent advantage of EIS is the real time observation for CAP-induced changes on intercellular junctions, with a label-free and in situ method manner.
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    Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole: PSS Hydrogels for Tissue Engineering
    (Weinheim : Wiley-VCH, 2021) Distler, Thomas; Polley, Christian; Shi, Fukun; Schneidereit, Dominik; Ashton, Mark D.; Friedrich, Oliver; Kolb, Jürgen F.; Hardy, John G.; Detsch, Rainer; Seitz, Hermann; Boccaccini, Aldo R.
    Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH