Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels
Abstract
Three-dimensional (3D) protein-patterned scaffolds provide a more biomimetic environment for cell culture than traditional two-dimensional surfaces, but simultaneous 3D protein patterning has proved difficult. We developed a method to spatially control the immobilization of different growth factors in distinct volumes in 3D hydrogels, and to specifically guide differentiation of stem/progenitor cells therein. Stem-cell differentiation factors sonic hedgehog (SHH) and ciliary neurotrophic factor (CNTF) were simultaneously immobilized using orthogonal physical binding pairs, barnase-barstar and streptavidin-biotin, respectively. Barnase and streptavidin were sequentially immobilized using two-photon chemistry for subsequent concurrent complexation with fusion proteins barstar-SHH and biotin-CNTF, resulting in bioactive 3D patterned hydrogels. The technique should be broadly applicable to the patterning of a wide range of proteins.
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Synthetic hydrogels can be functionalized with biologically active moieties that permit the growth and spread of cells; concentration and spacing of these cues can be changed independently.
“Synthetic hydrogels can be functionalized with biologically active moieties that permit the growth and spread of cells146–151; concentration and spacing of these cues can be changed independently152–155.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [152]
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- Authors
- Wylie, R. G., Ahsan, S., Aizawa, Y., Maxwell, K. L., Morshead, C. M., & Shoichet, M. S.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Shoichet, Molly S.
- Venue
- Nature Materials
- Published
- 2011-08-28
- Volume
- 10
- Issue
- 10
- Pages
- 799-806
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- OpenAlex
- W2122146362
- Cited by
- 480
- References
- 39
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 12 · 2023: 17 · 2022: 22 · 2021: 28 · 2020: 29 · 2019: 31 · 2018: 36 · 2017: 43 · 2016: 43 · 2015: 44 · 2014: 59 · 2013: 49 · 2012: 42
- FWCI
- 22.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP6279)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- growth factor immobilization, hydrogel scaffolds, stem cell differentiation, Sonic hedgehog, ciliary neurotrophic factor, biotin-streptavidin
- MeSH terms
- Bacterial Proteins, Biotin, Recombinant Fusion Proteins, Ribonucleases, Sepharose, Cell Culture Techniques, Streptavidin, Hydrogels, Ciliary Neurotrophic Factor, Intercellular Signaling Peptides and Proteins, Biomimetic Materials, Hedgehog Proteins, Tissue Scaffolds
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