Engineering organoids

Hofer, Moritz; Lutolf, Matthias P.

doi:10.1038/s41578-021-00279-y

Cited by 1,1843D Printing in Biomedical ResearchTissue Engineering and Regenerative MedicineCellular Mechanics and Interactions

Engineering organoids

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Hofer, Moritz, Lutolf, Matthias P.·2021·Nature Reviews Materials

DOI 10.1038/s41578-021-00279-yPMC PMC7893133

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Abstract

Organoids are in vitro miniaturized and simplified model systems of organs that have gained enormous interest for modelling tissue development and disease, and for personalized medicine, drug screening and cell therapy. Despite considerable success in culturing physiologically relevant organoids, challenges remain to achieve real-life applications. In particular, the high variability of self-organizing growth and restricted experimental and analytical access hamper the translatability of organoid systems. In this Review, we argue that many limitations of traditional organoid culture can be addressed by engineering approaches at all levels of organoid systems. We investigate cell surface and genetic engineering approaches, and discuss stem cell niche engineering based on the design of matrices that allow spatiotemporal control of organoid growth and shape-guided morphogenesis. We examine how microfluidic approaches and lessons learnt from organs-on-a-chip enable the integration of mechano-physiological parameters and increase accessibility of organoids to improve functional readouts. Applying engineering principles to organoids increases reproducibility and provides experimental control, which will, ultimately, be required to enable clinical translation.

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Organs-on-chips use a reductionist engineering strategy with predefined, targeted component design.
“OoCs follow a reductionist engineering approach through the targeted and pre-defined design of components”
From Human disease models in drug development (2023) · cites this paper as [24]
Matrigel has an ill-defined chemistry and composition, and major lot-to-lot variation, and thus offers poor control over ECM composition.
“Although Matrigel provides important biochemical cues, it has an ill-defined chemistry and composition, and major lot-to-lot variation [18,19], and thus offers a poor control over ECM composition [20].”
From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [18]

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Authors: Hofer, M., & Lutolf, M. P.
Affiliations: École Polytechnique Fédérale de Lausanne (CH)
ORCID: Hofer, Moritz
Lutolf, Matthias P.
Venue: Nature Reviews Materials
Publisher: Springer Science and Business Media LLC
Published: 2021-02-19
Volume: 6
Issue: 5
Pages: 402-420
ISSN: 2058-8437 (ISSN-L)
DOI: 10.1038/s41578-021-00279-y
PMC: PMC7893133
OpenAlex: W4211240480
Cited by: 1,184
References: 277
Citations by year: 2026: 189 · 2025: 275 · 2024: 256 · 2023: 226 · 2022: 168 · 2021: 70
FWCI: 15.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Materials (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders: National Science Foundation
European Commission (H2020-MSCA-ITN, H2020-MSCA-ITN-2018, HORIZON2020, H2020, 668294, MSCA-ITN-2018, H2020-MSCA)
École Polytechnique Fédérale de Lausanne
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (179447, 310030)
Vienna Science and Technology Fund
Board of the Swiss Federal Institutes of Technology
Horizon 2020 Framework Programme (MSCA‐ITN‐2018, H2020-MSCA, 668,294, H2020-MSCA-ITN-2018, H2020-MSCA-ITN)
Topics: Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords: organoids, organoid engineering, organoid culture, cell surface engineering, genetic engineering, morphogenesis, microfluidics, organ-on-a-chip, mechanobiology, reproducibility, translational medicine, drug screening, personalized medicine

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