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EDITORIAL
Extracellular matrix guides the fate of organoids

Nicholas G. Fischer 1,2,3 *

1 Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania,
United States of America
2 Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
3 Center for Innovation and Precision Dentistry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
*Corresponding author: Nicholas G. Fischer (nfi@seas.upenn.edu)

Citation: Fischer NG. Extracellular Cells without an extracellular matrix (ECM) are like performers without a stage—
matrix guides the fate of organoids. formless masses with no environment to enact their roles. The secreted ECM is
Organoid Res. 2025;1(3):025360028
doi: 10.36922/OR025360028 critical for organoid form and function, as cells exist in and continuously modify the
ECM, a complex assembly of proteins, glycosaminoglycans, and water that governs
Received: September 1, 2025
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processes across the spectrum of function from morphogenesis to repair. Alterations
Published online: October 30, 2025 in this tightly regulated system have profound consequences, exemplified by
2
Copyright: © 2025 Author(s). fibrosis, where excessive ECM deposition disrupts physiologic function. The ECM
This is an Open-Access article dictates bulk properties of tissues, such as the stiffness imparted by fibrous proteins,
distributed under the terms of the
Creative Commons Attribution directional strength arising from anisotropic collagen alignment, and elasticity
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License, permitting distribution, and from elastin. Despite its central role, the study of ECM has been constrained by
reproduction in any medium, which limited experimental platforms: in vivo analyses suffer from technical barriers to
provided that the original work is
properly cited. imaging, while conventional polystyrene culture systems fail to capture physiological
function. Therefore, experimental platforms must be designed to allow simultaneous
Publisher’s Note: AccScience investigation of cells and their secreted ECM to fully understand this dynamic
Publishing remains neutral with regard
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to jurisdictional claims in published reciprocity between cells and their secreted ECM.
maps and institutional affiliations.
A myriad of biomaterial systems have been developed to reproduce specific
aspects of ECM architecture and function. Traditional monophase hydrogels, for
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instance, may be engineered with tunable mechanical and biochemical cues, whereas
fibrous scaffolds fabricated by electrospinning or self-assembly better replicate
native architecture. These simplified platforms often present cells—typically a
single cell type—with only a uniform background, neglecting both the influence
of neighboring cell populations and the vast repository of ECM that cells naturally
secrete. Emerging evidence describes the critical importance of secreted ECM to
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the cellular interpretation of biomaterial platforms. As a result, traditional hydrogel
systems do not fully recapitulate the reciprocal feedback loops that define tissue-level
behavior. Organoid-based systems that are permissive to secreted ECM dynamics are
essential, as they allow cells to establish and modify their own microenvironment with
spatiotemporal precision while engaging in meaningful cross-talk with surrounding
cells, ideally multiple cell types, to better mimic tissue-level organization. Such
platforms provide a more physiologically relevant framework for studying the
interplay of cell–ECM interactions (Table 1).
Organoid systems engineered with biomaterials permissive to secreted
ECM—and the resultant dynamic reciprocity—have shown promise in studying
organoid maturation, organoid disease modeling, and organoid morphogenesis. For
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example, Chrisnandy and Lutolf demonstrated an eight-arm polyethylene glycol-
based culture system that supported the secretion of laminin-332 in intestinal organoid
culture, leading to the expression of regeneration and maturation markers and
organoid formation. Others have shown that hydrogel systems supportive of laminin
and collagen IV secretion supported alveolar organoid function. Radically simple
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Volume 1 Issue 3 (2025) 1 doi: 10.36922/OR025360028