@article{DoryabTaskinStahlhutetal.2021,
  author    = {Doryab, Ali and Taskin, Mehmet Berat and Stahlhut, Philipp and Schr{\"o}ppel, Andreas and Wagner, Darcy E. and Groll, J{\"u}rgen and Schmid, Otmar},
  title     = {A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface},
  series = {Advanced Functional Materials},
  volume    = {31},
  journal   = {Advanced Functional Materials},
  number    = {10},
  doi       = {10.1002/adfm.202004707},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225645},
  year      = {2021},
  abstract  = {Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε-)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (≤5 μm) is stretchable (up to 25\% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air-liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell-stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F-actin cytoskeleton filaments and tight junctions while non-physiologic over-stretch induces cell apoptosis, activates inflammatory response (IL-8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome.},
  language  = {en}
}
@article{DoryabTaskinStahlhutetal.2021,
  author    = {Doryab, Ali and Taskin, Mehmet Berat and Stahlhut, Philipp and Schr{\"o}ppel, Andreas and Orak, Sezer and Voss, Carola and Ahluwalia, Arti and Rehberg, Markus and Hilgendorff, Anne and St{\"o}ger, Tobias and Groll, J{\"u}rgen and Schmid, Otmar},
  title     = {A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions},
  series = {Frontiers in Bioengineering and Biotechnology},
  volume    = {9},
  journal   = {Frontiers in Bioengineering and Biotechnology},
  issn      = {2296-4185},
  doi       = {10.3389/fbioe.2021.616830},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223830},
  year      = {2021},
  abstract  = {Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) "breathing" lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35\% PCL and 6.34\% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10\% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.},
  language  = {en}
}