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

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

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

DOI 10.1038/nmat4219

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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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Authors: DeForest, C. A., & Tirrell, D. A.
Affiliations: California Institute of Technology (US)
Corresponding author: DeForest, Cole A.
Tirrell, David A.
ORCID: DeForest, Cole A.
Tirrell, David A.
Venue: Nature Materials
Publisher: Springer Science and Business Media LLC
Published: 2015-02-23
Volume: 14
Issue: 5
Pages: 523-531
ISSN: 1476-1122 (ISSN-L)
1476-4660
DOI: 10.1038/nmat4219
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels

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