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  4. Low-Defect Thiol-Michael Addition Hydrogels as Matrigel Substitutes for Epithelial Organoid Derivation
 
research article

Low-Defect Thiol-Michael Addition Hydrogels as Matrigel Substitutes for Epithelial Organoid Derivation

Rezakhani, Saba  
•
Gjorevski, Nikolce  
•
Lutolf, Matthias P.  
June 8, 2020
Advanced Functional Materials

Due to their selective crosslinking chemistry and well-defined mechano-biochemical characteristics, hydrogels crosslinked by thiol-Michael addition reactions have garnered immense interest for 3D cell culture applications. These hydrogels are typically formed via end-linking of bis-cysteine oligopeptides and branched f-functional (f >= 3) poly(ethylene glycol) (PEG). Unfortunately, this gel design accumulates excessive structural defects at a solid content below approximate to 10% (w/v) due to diluted bifunctional components reacting intramolecularly to form primary loops that compromise the gels' mechanical integrity and lead to excessive swelling. These limitations restrict the suitability of the gels for challenging cell culture applications, such as the growth of organoids. Here, low-defect thiol-Michael addition (LDTM) hydrogels based on novel building blocks designed toward minimizing structural defects are reported. Compared to the conventional gels, LDTM gels can be generated at an at least 2-fold lower solid content, while still incorporating high concentrations of bioactive ligands (approximate to 3 x 10(-3) m). LDTM gels promote the efficient development of fully patterned mouse intestinal organoids as well as human intestinal organoids, the latter in the absence of any animal-derived components. Powerful alternatives are thus provided to the gold-standard Matrigel, which is expensive and too variable for robust organoid development, facilitating translational applications of organoids.

  • Details
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Type
research article
DOI
10.1002/adfm.202000761
Web of Science ID

WOS:000538629900001

Author(s)
Rezakhani, Saba  
Gjorevski, Nikolce  
Lutolf, Matthias P.  
Date Issued

2020-06-08

Published in
Advanced Functional Materials
Article Number

2000761

Subjects

Chemistry, Multidisciplinary

•

Chemistry, Physical

•

Nanoscience & Nanotechnology

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Materials Science, Multidisciplinary

•

Physics, Applied

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Physics, Condensed Matter

•

Chemistry

•

Science & Technology - Other Topics

•

Materials Science

•

Physics

•

hydrogels

•

network architecture

•

organoids

•

peg

•

stem cells

•

thiol-michael addition

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cross-linking

•

stem-cells

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in-vitro

•

expansion

•

matrices

•

build

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPLUT  
Available on Infoscience
June 20, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/169482
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