3D extracellular matrix mimics: fundamental concepts and role of materials chemistry to influence stem cell fate
Abstract
Synthetic 3D extracellular matrices (ECMs) find application in cell studies, regenerative medicine, and drug discovery. While cells cultured in a monolayer may exhibit unnatural behavior and develop very different phenotypes and genotypes than in vivo, great efforts in materials chemistry have been devoted to reproducing in vitro behavior in in vivo cell microenvironments. This requires fine-tuning the biochemical and structural actors in synthetic ECMs. This review will present the fundamentals of the ECM, cover the chemical and structural features of the scaffolds used to generate ECM mimics, discuss the nature of the signaling biomolecules required and exploited to generate bioresponsive cell microenvironments able to induce a specific cell fate, and highlight the synthetic strategies involved in creating functional 3D ECM mimics.
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Additional ECM components are used as coating during cultivation to enhance cell adhesion, growth, and differentiation.
“Neuronal cells, particularly those derived from stem cells, require a supportive ECM environment that mimics their natural niche to maintain their viability, morphology, and function, which is why additional ECM components are used as coating during cultivation to enhance cell adhesion, growth, and differentiation (Friedl and Brocker, 2000; Theocharis et al., 2016; Nicolas et al., 2020).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Nicolas et al., 2020
Section 3 (page not provided) says ECM mimics can be used as surface coatings to promote cell adhesion. Section 2.1.2 says laminin is used as a coating to induce specific cell fates and functions and notes its role in neurite outgrowth. The passages do not establish that coatings enhance growth or that stem-cell-derived neuronal cells generally require such coatings to maintain viability, morphology, and function. (LLM, conf=0.82)
Experimental — accuracy not yet measuredNeuronal cells, particularly those derived from stem cells, require a supportive ECM environment that mimics their natural niche to maintain their viability, morphology, and function.
“Neuronal cells, particularly those derived from stem cells, require a supportive ECM environment that mimics their natural niche to maintain their viability, morphology, and function, which is why additional ECM components are used as coating during cultivation to enhance cell adhesion, growth, and differentiation (Friedl and Brocker, 2000; Theocharis et al., 2016; Nicolas et al., 2020).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Nicolas et al., 2020
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Ramakrishnan, R., Chouhan, D., Vijayakumar Sreelatha, H., Arumugam, S., Mandal, B. B., & Krishnan, L. K. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.2c00328 · Cited by 35 · see citing works
Advances in microfluidic 3D cell culture for preclinical drug development
(2022) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2021.07.022 · Cited by 23 · see citing works
Mclean, B., Ratcliffe, J., Parker, B. J., Field, E. H., Hughes, S. J., Cutter, S. W., Iseppi, K. J., Cameron, N. R., Binger, K. J., & Reynolds, N. P. (2024) · Biomacromolecules · doi:10.1021/acs.biomac.3c01013 · Cited by 6 · see citing works
Spänle, J. V., Haiber, L. M., & Seeger, B. (2026) · Frontiers in Toxicology · doi:10.3389/ftox.2026.1800157 · Cited by 1 · see citing works
- Authors
- Nicolas, J., Magli, S., Rabbachin, L., Sampaolesi, S., Nicotra, F., & Russo, L.
- Affiliations
- Institut Galien Paris-Saclay , , , ,
- University of Milano-Bicocca , , Piazza della Scienza 2 , ,
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-03-31
- Volume
- 21
- Issue
- 6
- Pages
- 1968-1994
- ISSN
- 1525-7797
- 1526-4602
- Cited by
- 504
- References
- 16
- Language
- en
- Funders
- H2020 Industrial Leadership (760986)
- Ministero della Salute (RF-2016-02362946)
- Regione Lombardia (NA)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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