Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics
Open accessAbstract
Biological processes are dynamic in nature, and growing evidence suggests that matrix stiffening is particularly decisive during development, wound healing and disease; yet, nearly all in vitro models are static. Here we introduce a step-wise approach, addition then light-mediated crosslinking, to fabricate hydrogels that stiffen (for example, ~3-30 kPa) in the presence of cells, and investigated the short-term (minutes-to-hours) and long-term (days-to-weeks) cell response to dynamic stiffening. When substrates are stiffened, adhered human mesenchymal stem cells increase their area from ~500 to 3,000 μm(2) and exhibit greater traction from ~1 to 10 kPa over a timescale of hours. For longer cultures up to 14 days, human mesenchymal stem cells selectively differentiate based on the period of culture, before or after stiffening, such that adipogenic differentiation is favoured for later stiffening, whereas osteogenic differentiation is favoured for earlier stiffening.
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Manipulating synthetic hydrogels using methods such as electrospinning, photopatterning, spraying of microspheres, inkjet and 3D printing, or microfluidic channels enables control over the shape and size of the organoids.
“Manipulating synthetic hydrogels using methods such as electrospinning125, photopatterning126,127, spraying of microspheres128, inkjet and 3D printing129, or microfluidic channels130 further enables control over the shape and size of the organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [127]
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- Authors
- Guvendiren, M., & Burdick, J. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Burdick, Jason A.
- ORCID
- Burdick, Jason A.
- Venue
- Nature Communications
- Published
- 2012-04-24
- Volume
- 3
- Issue
- 1
- Pages
- 792-792
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2069977719
- Cited by
- 707
- References
- 54
- Citations by year
- 2026: 40 · 2025: 36 · 2024: 50 · 2023: 56 · 2022: 47 · 2021: 63 · 2020: 60 · 2019: 51 · 2018: 55 · 2017: 53 · 2016: 50 · 2015: 48 · 2014: 41 · 2013: 45 · 2012: 11
- FWCI
- 21.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation (CAREER)
- David and Lucile Packard Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- matrix stiffening, dynamic hydrogels, mesenchymal stem cells, cell traction forces, cell adhesion, adipogenesis, osteogenic differentiation, extracellular matrix mechanics, mechanobiology, in vitro tissue models
- MeSH terms
- Biomechanical Phenomena, Cell Adhesion, Cell Movement, Cells, Cultured, Extracellular Matrix, Humans, Time Factors, Cell Culture Techniques, Hydrogels, Mesenchymal Stem Cells
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