Brain organoid formation on decellularized porcine brain ECM hydrogels
Open accessAbstract
Human brain tissue models such as cerebral organoids are essential tools for developmental and biomedical research. Current methods to generate cerebral organoids often utilize Matrigel as an external scaffold to provide structure and biologically relevant signals. Matrigel however is a nonspecific hydrogel of mouse tumor origin and does not represent the complexity of the brain protein environment. In this study, we investigated the application of a decellularized adult porcine brain extracellular matrix (B-ECM) which could be processed into a hydrogel (B-ECM hydrogel) to be used as a scaffold for human embryonic stem cell (hESC)-derived brain organoids. We decellularized pig brains with a novel detergent- and enzyme-based method and analyzed the biomaterial properties, including protein composition and content, DNA content, mechanical characteristics, surface structure, and antigen presence. Then, we compared the growth of human brain organoid models with the B-ECM hydrogel or Matrigel controls in vitro. We found that the native brain source material was successfully decellularized with little remaining DNA content, while Mass Spectrometry (MS) showed the loss of several brain-specific proteins, while mainly different collagen types remained in the B-ECM. Rheological results revealed stable hydrogel formation, starting from B-ECM hydrogel concentrations of 5 mg/mL. hESCs cultured in B-ECM hydrogels showed gene expression and differentiation outcomes similar to those grown in Matrigel. These results indicate that B-ECM hydrogels can be used as an alternative scaffold for human cerebral organoid formation, and may be further optimized for improved organoid growth by further improving protein retention other than collagen after decellularization.
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Simsa et al. discovered that hydrogels derived from decellularized adult porcine brain ECM (B-ECM) served as scaffolds for brain organoids derived from human embryonic stem cells (hESCs).
“Simsa et al. discovered that hydrogels derived from decellularized adult porcine brain ECM (B‐ECM) served as scaffolds for brain organoids derived from human embryonic stem cells (hESCs).”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [198]
They could be further optimized for organoid growth by enhancing the preservation of proteins beyond collagen after decellularization.
“They could be further optimized for organoid growth by enhancing the preservation of proteins beyond collagen after decellularization.[ 198 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [198]
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Dynamic hydrogel mechanics in organoid engineering: From matrix design to translational paradigms
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Microfluidic Brain‐on‐a‐Chip: From Key Technology to System Integration and Application
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A 3D bioprinted cortical organoid platform for modeling human brain development
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Silk scaffolding drives self-assembly of functional and mature human brain organoids
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Decellularized extracellular matrix for organoid and engineered organ culture
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Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review
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Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma
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Addressing Key Questions in Organoid Models: Who, Where, How, and Why?
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Modelling adult stem cells and their niche in health and disease with epithelial organoids
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The Role of Biophysical Factors in Organ Development: Insights from Current Organoid Models
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Osteomatrix as a personalized 3D tissue-specific invasion test-bed for oral carcinoma
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Mechanobiological engineering strategies for organoid culture
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Emerging brain organoids: 3D models to decipher, identify and revolutionize brain
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Development of Brain-Derived Bioscaffolds for Neural Progenitor Cell Culture
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Polyethylene Glycol‐Based Hydrogel as a 3D Extracellular Matrix Mimic for Cytotoxic T Lymphocytes
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Development of a Hydrogel Platform with GBM and Microglia: A Potential Glioblastoma Tumor Model
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The extracellular matrix as a dynamic regulator of brain function and plasticity
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Organoid scaffold materials: research and application
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Advances in Organoid Culture Research
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Brain Extracellular Matrix-Based Electronic Brain Biochip
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Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids
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Transformative potential of three-dimensional bioprinting technology for advanced organoid research
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Recent Development of Brain Organoids for Biomedical Application
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Extracellular Matrix Isolation: Sources and Methods
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Pluripotent stem cells-based neural organoids for modelling human brain development and diseases
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Biomaterials in Organoid Development
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Rethinking Neuroregenerative Microenvironments: Synergy Between Bioengineering and Organoids
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- Authors
- Simsa, R., Rothenbücher, T., Gürbüz, H., Ghosheh, N., Emneus, J., Jenndahl, L., Kaplan, D. L., Bergh, N., Serrano, A. M., & Fogelstrand, P.
- Affiliations
- Tufts University (US)
- Centro de Biología Molecular Severo Ochoa (ES)
- Technical University of Denmark (DK)
- University of Skövde (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Simsa, Robin
- Rothenbücher, Theresa
- Gürbüz, Hakan
- Ghosheh, Nidal
- Jenndahl, Lachmi
- Kaplan, David L.
- Bergh, Niklas
- Fogelstrand, Per
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2021-01-28
- Volume
- 16
- Issue
- 1
- Pages
- e0245685
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC7842896
- OpenAlex
- W3124422938
- Cited by
- 114
- References
- 72
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 24 · 2023: 27 · 2022: 21 · 2021: 6
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Diva portal (Dalarna University Library) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
- Funders
- Horizon 2020 (722779)
- MINECO SAF (2017-83241-R)
- ISC-III RETICS TerCel (RD16/0011/0032)
- ASCTN-Training (813851)
- National Institutes of Health (P41EB027062, R01NS092847)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- brain organoids, porcine brain, hydrogels, scaffold materials, human embryonic stem cells, Matrigel alternative, decellularization, collagen, protein retention, hydrogel rheology, organoid differentiation
- MeSH terms
- Human Embryonic Stem Cells, Animals, Brain, Brain Chemistry, Cell Line, Extracellular Matrix, Humans, Organoids, Swine, Hydrogels
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