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Synthetic hydrogels for human intestinal organoid generation and colonic wound repair
Open accessAbstract
In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multicellular three-dimensional structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumour-derived extracellular matrix (ECM), which severely limits the use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs, such that three-dimensional structures are never embedded in tumour-derived ECM. We also demonstrate that the hydrogel serves as an injection vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury.
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“Matrigel is mainly comprised of laminin, collagen IV, entactin, perlecan and growth factors, and is similar in composition to the basement membrane62.”
From Organoids (2022) · cites this paper as [62]
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“Therefore, other matrices with defined compositions64 have been explored as alternative matrices to Matrigel, such as recombinant human collagen62, fibrin65, or synthetic hydrogels3,63.”
From Organoids (2022) · cites this paper as [62]
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“These spheroids are being used to emulate organs such as the intestine2, liver3, kidney4, brain5, and heart6 to study human development and disease in vitro.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [2]
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“Organoid viability was reduced at high PEG density and matrix stiffness;”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
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“Intriguingly, when PEG was crosslinked with dithiothreitol to inhibit matrix degradation, organoid viability at seven days was poor as measured by live-dead staining.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
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“Cruz-Acuna and colleagues also found that PEG-based materials may need to be soft and degradable in order to support differentiated intestinal organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
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“RGD- or AG73 (CGGRKRLQVQLSIRT)-functionalized PEG matrices promoted greater organoid viability than laminin-derived IKVAV- or type I collagen-derived GFOGER peptides163,164.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [163]
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Metadata
- Authors
- Cruz-Acuña, R., Quirós, M., Farkas, A. E., Dedhia, P. H., Huang, S., Siuda, D., García-Hernández, V., Miller, A. J., Spence, J. R., Nusrat, A., & García, A. J.
- Affiliations
- University of Michigan (US)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Corresponding author
- Spence, Jason R.
- Nusrat, Asma
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2017-10-23
- Volume
- 19
- Issue
- 11
- Pages
- 1326-1335
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC5664213
- OpenAlex
- W2766832099
- Cited by
- 558
- References
- 38
- Citations by year
- 2026: 47 · 2025: 72 · 2024: 42 · 2023: 64 · 2022: 71 · 2021: 99 · 2020: 76 · 2019: 51 · 2018: 32 · 2017: 3
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Georgia Institute of Technology
- University of Georgia
- Crohn's and Colitis Foundation (326912)
- National Institutes of Health (UL1TR000454)
- National Heart, Lung, and Blood Institute (R01HL119215, R21HL115372)
- National Institute of General Medical Sciences (T32GM007315)
- National Institute of Allergy and Infectious Diseases (U19AI116482)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK085532, R01DK055679, R56DK089763, R29DK055679, R01DK059888, U01DK085532, U01DK103141, R01DK089763)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR062368, R01AR062920)
- National Institute of Dental and Craniofacial Research (T32DE007057)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007505)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- synthetic hydrogels, human intestinal organoids, pluripotent stem cells, organoid expansion, intestinal mucosal injury, regenerative medicine
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Colon, Extracellular Matrix, Humans, Intestinal Mucosa, Intestines, Organoids, Regeneration, Wound Healing, Hydrogels, Pluripotent Stem Cells, Mice
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