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Synthetic dynamic hydrogels promote degradation-independent in vitro organogenesis
Open accessAbstract
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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From Organoids (2022) · cites this paper as [67]
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Metadata
- Authors
- Chrisnandy, A., Blondel, D., Rezakhani, S., Broguiere, N., & Lutolf, M. P.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Venue
- Nature Materials
- Published
- 2021-11-15
- Volume
- 21
- Issue
- 4
- Pages
- 479-487
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- 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
- 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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