Cited by 513D Printing in Biomedical ResearchHydrogels: synthesis, properties, applicationsTissue Engineering and Regenerative Medicine

Scalable Production and Cryostorage of Organoids Using Core–Shell Decoupled Hydrogel Capsules

Open access
Lu, Yen‐Chun, Fu, Dah‐Jiun, An, Duo, Chiu, Alan, Schwartz, Robert, Nikitin, Alexander Yu., Ma, Minglin·2017·Advanced Biosystems

Abstract

Organoids, organ‐mimicking multicellular structures derived from pluripotent stem cells or organ progenitors, have recently emerged as an important system for both studies of stem cell biology and development of potential therapeutics; however, a large‐scale culture of organoids and cryopreservation for whole organoids, a prerequisite for their industrial and clinical applications, has remained a challenge. Current organoid culture systems relying on embedding the stem or progenitor cells in bulk extracellular matrix (ECM) hydrogels (e.g., Matrigel) have limited surface area for mass transfer and are not suitable for large‐scale productions. Here, a capsule‐based, scalable organoid production and cryopreservation platform is demonstrated. The capsules have a core–shell structure where the core consists of Matrigel that supports the growth of organoids, and the alginate shell forms robust spherical capsules, enabling suspension culture in stirred bioreactors. Compared with conventional, bulk ECM hydrogels, the capsules, which can be produced continuously by a two‐fluidic electrostatic cospraying method, provide better mass transfer through both diffusion and convection. The core–shell structure of the capsules also leads to better cell recovery after cryopreservation of organoids probably through prevention of intracellular ice formation.

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Crossref · 10.1002/adbi.201700165

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  • Several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.

    “In addition to organoids grown in naturally-derived proteins, several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.”

    From Towards organoid culture without Matrigel (2021) · cites this paper as [102]

  • Organoid types grown in alginate include human lung, human brain, murine intestinal, human intestinal, human pancreatic, and human and murine vascular.

    “Organoid types grown in alginate include human lung99,100, human brain101, murine intestinal102, human intestinal102,103, human pancreatic104, and human and murine vascular105.”

    From Towards organoid culture without Matrigel (2021) · cites this paper as [102]

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Research works printed but not linked: 3

  1. [38]Wang DH Souza RF Stem Cells, Pre-Neoplasia, Early Cancer Up Gastrointest Tract Jansen M Wright NA Springer International Publishing Cham 2016 183 212
  2. [41]Gjorevski N Sachs N Manfrin A Giger S Bragina E Ordóñez-Morán P Clevers H Lutolf MP Nat Publ Gr 2016 539 10.1038/nature20168 27851739 · DOI · Paper page
  3. [51]Sato T Vries RG Snippert HJ van de Wetering M Barker N Stange DE van Es JH Abo A Kujala P Peters PJ Clevers H Nature 2009 459 262 19329995

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Authors
Lu, Y., Fu, D., An, D., Chiu, A., Schwartz, R., Nikitin, A. Y., & Ma, M.
Affiliations
Cornell University (US)
Corresponding author
Ma, Minglin
Venue
Advanced Biosystems
Publisher
Wiley
Published
2017-11-22
Volume
1
Issue
12
ISSN
2366-7478 (ISSN-L)
OpenAlex
W2770441697
Cited by
51
References
53
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 10 · 2021: 7 · 2020: 5 · 2019: 9 · 2018: 1
FWCI
1.85
Type
journal article
Language
en
Open access
Locations
  • Advanced Biosystems (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (1R03EB020910‐01, 1R01CA182413, 1R01CA197160)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
organoids, Matrigel, suspension culture, stirred tank reactor, mass transfer, intracellular ice formation, cell recovery, pluripotent stem cells

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