Cell-Laden Agarose-Collagen Composite Hydrogels for Mechanotransduction Studies

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Date
2020Type
- Journal Article
Citations
Cited 22 times in
Web of Science
Cited 24 times in
Scopus
ETH Bibliography
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Abstract
The increasing investigation of cellular mechanotransduction mechanisms requires biomaterials combining biofunctionality and suitable mechanical properties. Agarose is a standard biomaterial for cartilage and intervertebral disc mechanobiology studies, but lacks adhesion motifs and the necessary cell-matrix interaction for mechanotransduction. Here, collagen type I was blended at two concentrations (2 and 4.5 mg/mL) with agarose 2% wt/vol. The composite hydrogels were characterized in terms of structural homogeneity, rheological properties and size stability. Nucleus pulposus (NP) cell viability, proliferation, morphology, gene expression, GAG production, adhesion and mechanotransduction ability were further tested. Blended hydrogels presented a homogenous network of the two polymers. While the addition of 4.5 mg/mL collagen significantly decreased the storage modulus and increased the loss modulus of the gels, blended gels containing 2 mg/mL collagen displayed similar mechanical properties to agarose. Hydrogel size was conserved over 21 days for all agarose-based gels. Embedded cells were viable (>80%) and presented reduced proliferation and a round morphology typical of NP cells in vivo. Gene expression of collagen types I and II and aggrecan significantly increased in blended hydrogels from day 1 to 7, further resulting in a significantly superior GAG/DNA ratio compared to agarose gels at day 7. Agarose-collagen hydrogels not only promoted cell adhesion, contrary to agarose gels, but also showed a 5.36-fold higher focal adhesion kinase phosphorylation (pFAK/β-tubulin) when not compressed, and increased pFAK/FAK values 10 min after compression. Agarose-collagen thus outperforms agarose, mimics native tissues constituted of non-fibrillar matrix and collagens, and allows exploring complex loading in a highly reproducible system. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000414697Publication status
publishedExternal links
Journal / series
Frontiers in Bioengineering and BiotechnologyVolume
Pages / Article No.
Publisher
Frontiers MediaSubject
Blended hydrogels; Agarose; Collagen; Mechanobiology; Extracellular matrix; Dynamic compression; Focal adhesion kinaseOrganisational unit
09597 - Würtz, Karin (SNF-Professur) (ehemalig) / Würtz, Karin (SNF-Professur) (former)
03915 - Ferguson, Stephen / Ferguson, Stephen
Funding
163678 - Unlocking the mechanisms of mechanotransduction in degenerative disc disease (TRIPDISC) (SNF)
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Show all metadata
Citations
Cited 22 times in
Web of Science
Cited 24 times in
Scopus
ETH Bibliography
yes
Altmetrics