Speaker
Description
Over the past 15 years, our group has focused on the development of advanced lung-on-chip (LOC) models that closely mimic the human lung parenchyma with high physiological relevance. Our early systems[1],[2], which replicated the three-dimensional deflection associated with physiological breathing motions, have since been commercialized by our spin-off company, AlveoliX. These foundational models paved the way for a second-generation LOC platform featuring a membrane composed of collagen and elastin—two key extracellular matrix proteins—structured into an array of alveoli-sized compartments, thereby replacing the flexible and porous PDMS membrane[3],[4].
More recently, we have employed these platforms for the toxicological assessment of airborne substances such as disinfectants[5] and cigarette smoke (Sengupta et al., in revision). Our studies revealed a critical synergy between mechanical stress and the air-liquid interface in disrupting the integrity of the alveolar air-blood barrier, as evidenced by significant reductions in trans-epithelial electrical resistance (TEER), among other indicators.
Additionally, we have developed an idiopathic pulmonary fibrosis (IPF) model on-chip, which not only recapitulates fibrotic-like tissue remodeling but also demonstrates how cyclic mechanical strain significantly influences the therapeutic response to nintedanib (Weber et al., submitted). Together, these findings highlight the essential role of biomechanical cues in shaping both toxicological outcomes and drug efficacy, underscoring the need for physiologically dynamic in vitro pulmonary models in respiratory research.
[1] Stucki AO, Stucki JD, Hall SR, Felder M, Mermoud Y, Schmid RA, Geiser T, Guenat OT. A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Lab Chip. 2015 Mar 7;15(5):1302-10.
[2] Stucki JD, Hobi N, Galimov A, Stucki AO, Schneider-Daum N, Lehr CM, Huwer H, Frick M, Funke-Chambour M, Geiser T, Guenat OT. Medium throughput breathing human primary cell alveolus-on-chip model. Sci Rep. 2018 Sep 25;8(1):14359.
[3] Zamprogno P, Wüthrich S, Achenbach S, Thoma G, Stucki JD, Hobi N, Schneider-Daum N, Lehr CM, Huwer H, Geiser T, Schmid RA, Guenat OT. Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane. Commun Biol. 2021 Feb 5;4(1):168.
[4] Zamprogno P, Thoma G, Cencen V, Ferrari D, Putz B, Michler J, Fantner GE, Guenat OT. Mechanical Properties of Soft Biological Membranes for Organ-on-a-Chip Assessed by Bulge Test and AFM. ACS Biomater Sci Eng. 2021 Jul 12;7(7):2990-2997.
[5] Sengupta A, Dorn A, Jamshidi M, Schwob M, Hassan W, De Maddalena LL, Hugi A, Stucki AO, Dorn P, Marti TM, Wisser O, Stucki JD, Krebs T, Hobi N, Guenat OT. A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip. Front Pharmacol. 2023 Mar 6;14:1114739.
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