Cited by 432Hydrogels: synthesis, properties, applications3D Printing in Biomedical ResearchCellular Mechanics and Interactions

A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels

DeForest, Cole A., Tirrell, David A.·2015·Nature Materials

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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Crossref · 10.1038/nmat4219

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55 of 55 references verified0 citation errors · 0 not checkable

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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 [155]

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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
  • 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
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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