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- ItemReconstruction of Ultra-thin Alveolar-capillary Basement Membrane Mimics(Weinheim : Wiley-VCH, 2021) Jain, Puja; Nishiguchi, Akihiro; Linz, Georg; Wessling, Matthias; Ludwig, Andreas; Rossaint, Rolf; Möller, Martin; Singh, SmritiAlveolar-capillary basement membrane (BM) is ultra-thin (<2 µm) extracellular matrix that maintains integral epithelial-endothelial cell layers. In vitro reconstructions of alveolar-capillary barrier supported on synthetic scaffolds closely resembling the fibrous and ultra-thin natural BM are essential in mimicking the lung pathophysiology. Although BM topology and dimensions are well known to significantly influence cellular behavior, conventionally used BM mimics fail to recreate this natural niche. To overcome this, electrospun ultra-thin 2 µm poly(caprolactone) (PCL) nanofibrous mesh is used to establish an alveolar-capillary barrier model of lung endothelial/epithelial cells. Transepithelial electrical resistance (TEER) and permeability studies reveal integral tight junctions and improved mass transport through the highly porous PCL meshes compared to conventional dense membranes with etched pores. The chemotaxis of neutrophils is shown across the barrier in presence of inflammatory response that is naturally impeded in confined regions. Conventional requirement of 3 µm or larger pore size can lead to barrier disruption due to epithelial/endothelial cell invasion. Despite high porosity, the interconnected BM mimic prevents barrier disruption and allows neutrophil transmigration, thereby demonstrating the physiological relevance of the thin nanofibrous meshes. It is envisioned that these bipolar cultured barriers would contribute to an organ-level in vitro model for pathological disease, environmental pollutants, and nanotoxicology. © 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH
- Item3D‐Printed Bioreactor with Integrated Impedance Spectroscopy for Cell Barrier Monitoring(Weinheim : Wiley, 2021) Linz, Georg; Rauer, Sebastian Bernhard; Kuhn, Yasmin; Wennemaring, Simon; Siedler, Laura; Singh, Smriti; Wessling, MatthiasCell culture experiments often suffer from limited commercial availability of laboratory-scale bioreactors, which allow experiments to be conducted under flow conditions and additional online monitoring techniques. A novel 3D-printed bioreactor with a homogeneously distributed flow field enabling epithelial cell culture experiments and online barrier monitoring by integrated electrodes through electrical impedance spectroscopy (EIS) is presented. Transparent and conductive indium tin oxide glass as current-injecting electrodes allows direct visualization of the cells, while measuring EIS simultaneously. The bioreactor's design considers the importance of a homogeneous electric field by placing the voltage pick-up electrodes in the electrical field. The device's functionality is demonstrated by the cultivation of the epithelial cell line Caco-2 under continuous flow and monitoring of the cell layer by online EIS. The collected EIS data were fitted by an equivalent electric circuit, resulting in the cell layer's resistance and capacitance. This data is used to monitor the cell layer's reaction to ethylene glycol-bis-(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid and forskolin. These two model substances show the power of impedance spectroscopy as a non-invasive way to characterize cell barriers. In addition, the bioreactor design is available as a print-ready file in the Appendix, enabling its use for other scientific institutions.
- Item3D-Printing of Structure-Controlled Antigen Nanoparticles for Vaccine Delivery(Columbus, Ohio : American Chemical Soc., 2020) Nishiguchi, Akihiro; Shima, Fumiaki; Singh, Smriti; Akashi, Mitsuru; Moeller, MartinTargeted delivery of antigens to immune cells using micro/nanocarriers may serve as a therapeutic application for vaccination. However, synthetic carriers have potential drawbacks including cytotoxicity, low encapsulation efficiency of antigen, and lack of a morphological design, which limit the translation of the delivery system to clinical use. Here, we report a carrier-free and three-dimensional (3D)-shape-designed antigen nanoparticle by multiphoton lithography-based 3D-printing. This simple, versatile 3D-printing approach provides freedom for the precise design of particle shapes with a nanoscale resolution. Importantly, shape-designed antigen nanoparticles with distinct aspect ratios show shape-dependent immune responses. The 3D-printing approach for the rational design of nanomaterials with increasing safety, complexity, and efficacy offers an emerging platform to develop vaccine delivery systems and mechanistic understanding.
- ItemBioactive Nanogels Mimicking the Antithrombogenic Nitric Oxide-Release Function of the Endothelium(Weinheim : Wiley-VCH, 2023) Hosseinnejad, Aisa; Ludwig, Nadine; Mersmann, Sina; Winnerbach, Patrick; Bleilevens, Christian; Rossaint, Rolf; Rossaint, Jan; Singh, SmritiNitric oxide (NO) plays a significant role in controlling the physiology and pathophysiology of the body, including the endothelial antiplatelet function and therefore, antithrombogenic property of the blood vessels. This property of NO can be exploited to prevent thrombus formation on artificial surfaces like extracorporeal membrane oxygenators, which when come into contact with blood lead to protein adsorption and thereby platelet activation causing thrombus formation. However, NO is extremely reactive and has a very short biological half-life in blood, so only endogenous generation of NO from the blood contacting material can result into a stable and kinetically controllable local delivery of NO. In this regards, highly hydrophilic bioactive nanogels are presented which can endogenously generate NO in blood plasma from endogenous NO-donors thereby maintaining a physiological NO flux. It is shown that NO releasing nanogels could initiate cGMP-dependent protein kinase signaling followed by phosphorylation of vasodilator-stimulated phosphoprotein in platelets. This prevents platelet activation and aggregation even in presence of highly potent platelet activators like thrombin, adenosine 5′-diphosphate, and U46619 (thromboxane A2 mimetic).
- ItemPhysical gels of poly(vinylamine) by thermal curing(Cambridge : Royal Society of Chemistry, 2020) Fischer, Thorsten; Köhler, Jens; Möller, Martin; Singh, SmritiPhysical gels are a versatile class of materials which can find application in sensors, electrochemistry, biomedicine or rheological modifiers. Herein, we present a hydrogen-bonded physical gel which is based on the interaction between phenylcarbonate telechelic poly(ethylene glycol) (PEG-PC) and poly(vinyl amine-co-acetamide) (p(VAm-co-VAA)). The critical gelation concentration was found to be 10 wt% by rheology and NMR. UV-vis spectroscopy and dynamic light scattering reveal the formation of aggregates in the gel. Rheology and differential scanning calorimetry (DSC) was used to show the effect of thermal curing on the mechanical properties of the physical gel. © The Royal Society of Chemistry 2020.