Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels
By Sudhir Khetan, M. Guvendiren, W. Legant, Daniel M. Cohen, Christopher S. Chen, Jason A. Burdick. Nature Materials, 2013
1,098 citations recorded by the source corpus.
Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional (3D) encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular-traction, independent of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that either permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). In addition, switching the permissive hydrogel to a restrictive state via delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Also, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.
Subfields: Biomedical Engineering, Cell Biology, Orthopedics and Sports Medicine
View Paper: https://www.semanticscholar.org/paper/f63201cf37bae77a4e75837d77c0120a67cec4f7
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Citations in the corpus
- Overview of natural hydrogels for regenerative medicine applications (2019, background): “As mentioned earlier this parameter must be characterized according to the hydrogels’ designed application [10], as this property alone can significantly change the hydrogels’ characteristics [11].”
- A Review of Cell Adhesion Studies for Biomedical and Biological Applications (2015, background): “Bead dispersion in the 3D gel will be observed to estimate the cellular contractility of the cell during migration [63–67].”
- Review on Cell Mechanics: Experimental and Modeling Approaches (2013, methodology): “More recently, this technique has been combined with laser scanning confocal microscopy to allow for the measurement of traction forces in three dimensions [391] [392] [393] [394] [395].”
- Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs (2017, background): “Cell suspension inks based on cell aggregates are a viable option to create scaffold-free biological constructs (Forgacs and Foty, 2004; Marga et al., 2007).”