Cited by 237Hydrogels: synthesis, properties, applications3D Printing in Biomedical ResearchCellular Mechanics and Interactions

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Synthetic dynamic hydrogels promote degradation-independent in vitro organogenesis

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Chrisnandy, Antonius, Blondel, Delphine, Rezakhani, Saba, Broguiere, Nicolas, Lutolf, Matthias P.·2022·Nature Materials

DOI 10.1038/s41563-021-01136-7

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Abstract

Epithelial organoids are most efficiently grown from mouse-tumour-derived, reconstituted extracellular matrix hydrogels, whose poorly defined composition, batch-to-batch variability and immunogenicity limit clinical applications. Efforts to replace such ill-defined matrices for organoid culture have largely focused on non-adaptable hydrogels composed of covalently crosslinked hydrophilic macromolecules. However, the excessive forces caused by tissue expansion in such elastic gels severely restrict organoid growth and morphogenesis. Chemical or enzymatic degradation schemes can partially alleviate this problem, but due to their irreversibility, long-term applicability is limited. Here we report a family of synthetic hydrogels that promote extensive organoid morphogenesis through dynamic rearrangements mediated by reversible hydrogen bonding. These tunable matrices are stress relaxing and thus promote efficient crypt budding in intestinal stem-cell epithelia through increased symmetry breaking and Paneth cell formation dependent on yes-associated protein 1. As such, these well-defined gels provide promising versatile matrices for fostering elaborate in vitro morphogenesis.

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Authors: Chrisnandy, A., Blondel, D., Rezakhani, S., Broguiere, N., & Lutolf, M. P.
Affiliations: École Polytechnique Fédérale de Lausanne (CH)
ORCID: Chrisnandy, Antonius
Rezakhani, Saba
Broguiere, Nicolas
Lutolf, Matthias P.
Venue: Nature Materials
Publisher: Springer Science and Business Media LLC
Published: 2021-11-15
Volume: 21
Issue: 4
Pages: 479-487
ISSN: 1476-1122 (ISSN-L)
1476-4660
DOI: 10.1038/s41563-021-01136-7
OpenAlex: W3211744428
Cited by: 237
References: 53
Citations by year: 2026: 32 · 2025: 59 · 2024: 54 · 2023: 55 · 2022: 35 · 2021: 2
FWCI: 11.52
Type: journal article
Language: en
Open access: green
infoscience.epfl.ch
Licence: cc-by-nc-nd
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Materials (publishedVersion)
PubMed (publishedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Topics: Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords: synthetic hydrogels, dynamic hydrogels, stress relaxation, intestinal organoids, symmetry breaking, Paneth cells, YAP, extracellular matrix, tissue expansion
MeSH terms: Animals, Extracellular Matrix, Organoids, Stem Cells, Hydrogels, Organogenesis, Mice

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Synthetic dynamic hydrogels promote degradation-independent in vitro organogenesis

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