Low-density electrospun fibrous network promotes mechanotransduction and matrix remodeling in fibroblasts.

Summary

Using a low-density electrospun fiber network, the authors show that fibroblasts adopt a contractile, matrix-remodeling phenotype with upregulation of ECM-related transcripts and proteins. Mechanistically, RhoA-ROCK signaling, YAP nuclear translocation, and Piezo1 activation drive enhanced mechanotransduction; ROCK inhibition abrogated remodeling capacity.

Key Findings

• Low-density electrospun networks induced a contractile fibroblast phenotype with increased ECM-related gene and protein expression.
• RhoA-ROCK pathway activation, YAP nuclear translocation, and Piezo1 activation mediated enhanced mechanotransduction.
• ROCK inhibition disrupted mechanotransduction and impaired matrix-remodeling capacity.

Clinical Implications

Designing low-density, compliant fibrous scaffolds may enhance dermal matrix remodeling for wound healing and aesthetic skin regeneration (e.g., scar modulation, anti-aging).

Limitations

• In vitro study without in vivo validation of remodeling outcomes
• Limited quantitative characterization of network mechanical parameters across conditions

Future Directions

Validate scaffold-guided remodeling in vivo (skin/wound models) and map fiber density, stiffness, and architecture design space to optimize mechanotransduction.