Conclusion
These observations may provide insights into tissue repair processes in vivo and motivate the incorporation of cell-adhesive fibers within synthetic hydrogels for material-guided wound repair strategies.
Methods
We employed a 3D, fibrous and protease-sensitive hydrogel model of interstitial ECM to study the interplay between Rho GTPases and fibrous matrix cues in fibroblasts during wound healing.
Results
Modulating fiber density within protease-sensitive hydrogels, we confirmed previous findings that heightened fiber density promotes fibroblast spreading and proliferation. The presence of matrix fibers furthermore corresponded to increased cell migration speeds and macroscopic hydrogel contraction arising from fibroblast generated forces. During fibroblast spreading, Rac1 and RhoA GTPase activity proved crucial for fiber-mediated cell spreading and contact guidance along matrix fibers, while Cdc42 was dispensable. In contrast, interplay between RhoA, Rac1, and Cdc42 contributed to fiber-mediated myofibroblast differentiation and matrix contraction over longer time scales.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12195-021-00698-5.