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Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels.

Nat Mater. 2013; 
Khetan S, Guvendiren M, Legant WR, Cohen DM, Chen CS, Burdick JA.
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Peptide Synthesis The integrin-binding peptide GCGYRGD SPG (Genscript; italics indicates the cell-adhesive domain) was conjugated to MeHA, MeAlg and MeDex (754 µM, matching that used in the described physically crosslinked alginate studies), and to MeMaHA (1 mM) through 30 min reaction in pH 8.... Passage 3 hMSCs (Lonza) were encapsulated either into MeMaHA (1 million hMSCs ml−1 ) hydrogels using Michael addition reactions between MeMaHA maleimides and the MMP degradable peptide GCRDVP MS↓MRGGDRCG (Genscript; down arrow indicates cleavage site by MMP-2), or into MeHA, MeAlg or MeDex (15 million hMSCs ml−1 ) using photoinitiated free-radical polymerization (Exfo Omnicure S1000 lamp with a 320–390 nm filter, exposure of 10 mW cm−2 for 5 min) in the presence of 0. Get A Quote

摘要

Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional 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, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, swi... More

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