A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface

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A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface. / Doryab, Ali; Taskin, Mehmet Berat; Stahlhut, Philipp; Schröppel, Andreas; Wagner, Darcy E.; Groll, Jürgen; Schmid, Otmar.

In: Advanced Functional Materials, Vol. 31, No. 10, 2004707, 2021.

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Doryab, Ali ; Taskin, Mehmet Berat ; Stahlhut, Philipp ; Schröppel, Andreas ; Wagner, Darcy E. ; Groll, Jürgen ; Schmid, Otmar. / A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface. In: Advanced Functional Materials. 2021 ; Vol. 31, No. 10.

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TY - JOUR

T1 - A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface

AU - Doryab, Ali

AU - Taskin, Mehmet Berat

AU - Stahlhut, Philipp

AU - Schröppel, Andreas

AU - Wagner, Darcy E.

AU - Groll, Jürgen

AU - Schmid, Otmar

PY - 2021

Y1 - 2021

N2 - 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 (0.5 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.

AB - 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 (0.5 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.

KW - alveolar-capillary barrier

KW - cyclic mechanical stretch

KW - hybrid polymers

KW - in vitro cell-stretch model

KW - tunable ultra-thin biphasic membrane

UR - http://www.scopus.com/inward/record.url?scp=85096761686&partnerID=8YFLogxK

U2 - 10.1002/adfm.202004707

DO - 10.1002/adfm.202004707

M3 - Article

AN - SCOPUS:85096761686

VL - 31

JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-3028

IS - 10

M1 - 2004707

ER -