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A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels
Abstract
Although biochemically patterned hydrogels are capable of recapitulating many critical aspects of the heterogeneous cellular niche, exercising spatial and temporal control of the presentation and removal of biomolecular signalling cues in such systems has proved difficult. Here, we demonstrate a synthetic strategy that exploits two bioorthogonal photochemistries to achieve reversible immobilization of bioactive full-length proteins with good spatial and temporal control within synthetic, cell-laden biomimetic scaffolds. A photodeprotection-oxime-ligation sequence permits user-defined quantities of proteins to be anchored within distinct subvolumes of a three-dimensional matrix, and an ortho-nitrobenzyl ester photoscission reaction facilitates subsequent protein removal. By using this approach to pattern the presentation of the extracellular matrix protein vitronectin, we accomplished reversible differentiation of human mesenchymal stem cells to osteoblasts in a spatially defined manner. Our protein-patterning approach should provide further avenues to probe and direct changes in cell physiology in response to dynamic biochemical signalling.
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“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 [155]
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Self-citation
Metadata
- Authors
- DeForest, C. A., & Tirrell, D. A.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- DeForest, Cole A.
- Tirrell, David A.
- Venue
- Nature Materials
- Published
- 2015-02-23
- Volume
- 14
- Issue
- 5
- Pages
- 523-531
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- OpenAlex
- W2088868630
- Cited by
- 432
- References
- 55
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 23 · 2023: 33 · 2022: 21 · 2021: 52 · 2020: 55 · 2019: 49 · 2018: 68 · 2017: 54 · 2016: 33 · 2015: 8
- FWCI
- 22.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › 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
- protein immobilization, three-dimensional hydrogels, cell-laden scaffolds, vitronectin, mesenchymal stem cells, osteogenic differentiation, biomimetic scaffolds
- MeSH terms
- Cell Differentiation, Humans, Osteoblasts, Vitronectin, Hydrogels, Biomimetic Materials, Tissue Scaffolds, Photochemical Processes, Immobilized Proteins, Mesenchymal Stem Cells
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