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Zhang, J.* ; Marciano, D.* ; Wang, L.* ; Wang, W.* ; Gossen, M.* ; Yang, M.* ; Peng, T. ; Gautrot, J.* ; Xu, X.* ; Ma, N.*

Bioinspired hyaluronica acid-based hydrogel fuels bi-directional lung organoid maturation via PIEZO1 and ITGB1 mediated mechanosensation.

Adv. Mater. Interfaces, DOI: 10.1002/admi.202400194 (2024)
Publ. Version/Full Text DOI
Open Access Gold
Creative Commons Lizenzvertrag
Lung diseases are one of the leading causes of global mortality. Advances in induced pluripotent stem cell (iPSC) differentiation have enabled the creation of bronchiolar and alveolar lung organoids, advancing research on lung conditions. Traditional Matrigel encapsulation, reliant on the spontaneous assembly and propagation of cells with limited external intervention, often results in variability and low reproducibility. The absence of hyaluronic acid (HA) in Matrigel, a key lung extracellular matrix component, limits bronchiolar and alveolar cell differentiation, reducing the efficacy and reproducibility of iPSC-derived organoid generation. To address this, a novel hybrid hydrogel combining HA and 23% Matrigel, inspired by the natural lung environment, is developed. This hydrogel offers improved biochemical support and viscoelastic properties, significantly accelerating organoid development. Within eight days, the hydrogel produces uniformly sized organoids containing both bronchiolar and alveolar epithelial cells. Increased levels of active mechanosensors and transducers, including PIEZO1, Integrin, and Myosin, suggest that the hydrogel's altered viscoelasticity triggers a mechanotransduction cascade. This bioinspired hydrogel provides a robust, fast model for biomedical research, facilitating rapid drug screening, respiratory disease treatment studies, and surfactant trafficking investigations. Furthermore, it enables the exploration of underlying biomechanical mechanisms to enhance the controllability of organoid generation and maturation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Biomechanics ; Hyaluronic Acid (ha) ; Hydrogel ; Lung Organoid ; Piezo1; Actomyosin Contractility; Epithelial-cells; Progenitor Cells; Differentiation; Generation; Regeneration; Mechanisms; Models
ISSN (print) / ISBN 2196-7350
e-ISSN 2196-7350
Journal Advanced Materials Interfaces
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants Helmholtz Association - Munich School for Data Science (MUDS)
Helmholtz Imaging Project "AIOrganoid", China Scholarship Council
Helmholtz Association of German Research Centers