Organic electronic ion pumps (OEIPs) are a versatile tool for electrophoretic delivery of substances with high spatiotemporal resolution. To date, OEIPs and similar iontronic components have been fabricated using thin-film techniques, and often rely on laborious, multistep photolithographic processes. OEIPs have been demonstrated in a variety of in vitro and in vivo settings for controlling biological systems, but the thin-film form factor and limited repertoire of polyelectrolyte materials and device fabrication techniques unnecessarily constrain the possibilities for miniaturization and extremely localized substance delivery, e.g., the greater range of pharmaceutical compounds, on the scale of a single cell. Here, we demonstrate an entirely new OEIP form factor based on capillary fibers that include hyperbranched polyglycerols (dPGs) as the selective electrophoretic membrane. The dPGs enable electrophoretic channels with high concentration of fixed charges, well-controlled cross-linking, and can be realized using a simple "one-pot" fluidic manufacturing protocol. Selective electrophoretic transport of cations and anions of various sizes is demonstrated, including "large" substances difficult to transport with other OEIP technologies. We present a method for tailoring and characterizing the electrophoretic channels' fixed charge concentration in the operational state. Subsequently, we compare the experimental performance of these capillary-OEIPs to a computational model and are able to explain unexpected features in the ionic current for the transport and delivery of larger, lower mobility ionic compounds. From the model, we are able to elucidate several operational and design principles relevant for miniaturized electrophoretic drug delivery technologies in general. Overall, the compactness of the capillary-OEIP enables electrophoretic delivery devices with probe-like geometries, suitable for a variety of ionic compounds, paving the way for less-invasive implantation into biological systems and for healthcare applications.
High costs are a key challenge in “democratization” of organ-chip research. We present a low-resource barrier-on-chip based on tape, and use it to model small intestine and its response to chili peppers (capsaicinoids).
Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human‐like models for biopharmaceutical research. In this study, the first such model of the blood‐brain barrier (BBB‐on‐chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)‐derived cells and continuous barrier integrity monitoring with <2 min temporal resolution is reported. Its capabilities are showcased in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off‐stoichiometry thiol–ene–epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell–substrate endothelial resistance monitoring allows for capturing the formation and breakdown of the BBB model, which consists of cocultured hiPSC‐derived endothelial‐like and astrocyte‐like cells. Clear cellular disruption is observed when exposing the BBB‐on‐chip to the nitrosative stressor linsidomine, and the barrier permeability and barrier‐protective effects of the antioxidant N‐acetylcysteine amide are reported. Using metabolomic network analysis reveals further drug‐induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like this opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human‐derived cells and providing high‐resolution temporal readouts that can help in pharmacodynamic studies.
Astrocytes play an important role in the central nervous system, contributing to the development of and maintenance of synapses, recycling of neurotransmitters, and the integrity and function of the blood–brain barrier. Astrocytes are also linked to the pathophysiology of various neurodegenerative diseases. Astrocyte function and organization are tightly regulated by interactions mediated by the extracellular matrix (ECM). Engineered hydrogels can mimic key aspects of the ECM and can allow for systematic studies of ECM-related factors that govern astrocyte behaviour. In this study, we explore the interactions between neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. Morphological analysis reveals that FPA have a higher degree of interactions with the hyaluronan-based gels compared to the cell lines. This interaction is enhanced by conjugation of cell-adhesion peptides (cRGD and IKVAV) to the hyaluronan backbone. These effects are retained and pronounced in 3D bioprinted structures. Bioprinted FPA using cRGD functionalized hyaluronan show extensive and defined protrusions and multiple connections between neighboring cells. Possibilities to tailor and optimize astrocyte-compatible ECM-mimicking hydrogels that can be processed by means of additive biofabrication can facilitate the development of advanced tissue and disease models of the central nervous system.
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