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Generation of a Three-dimensional Full Thickness Skin Equivalent and Automated Wounding
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Repeated folding stress-induced morphological changes in the dermal equivalent.

Koji Y Arai1, Mami Sugimoto, Kanako Ito

  • 1Scleroprotein Research Institute, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [And] International Society for Digital Imaging of Skin (ISDIS) [And] International Society for Skin Imaging (ISSI)
|February 11, 2014
PubMed
Summary

Repeated mechanical stress causes skin to contract by activating the RhoA-ROCK pathway, leading to wrinkles. This study investigated the underlying mechanisms in a dermal equivalent model.

Keywords:
dermal equivalentfibroblastmechanical stressskin furrow/wrinkle

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Area of Science:

  • Dermatology
  • Biomechanical Engineering
  • Molecular Biology

Background:

  • Skin aging and wrinkle formation are linked to repeated mechanical stresses.
  • The precise molecular mechanisms driving these morphological changes remain unclear.

Purpose of the Study:

  • To investigate the effects of repeated mechanical stress on a dermal equivalent.
  • To elucidate the cellular and molecular pathways involved in stress-induced skin changes.

Main Methods:

  • Developed a novel device for applying repeated folding stress to a dermal equivalent.
  • Analyzed morphological changes, collagen fibril orientation, and gene expression.
  • Assessed the role of the RhoA-ROCK signaling pathway using a specific inhibitor.

Main Results:

  • Repeated folding stress significantly decreased dermal equivalent width.
  • Mechanical stress altered collagen fibril orientation but did not affect collagen content or cell viability.
  • Inhibition of Rho-associated coiled-coil-containing kinase (ROCK) completely prevented width reduction.

Conclusions:

  • The decrease in dermal equivalent width is due to unidirectional contraction, not collagen degradation or cell loss.
  • The RhoA-ROCK signaling pathway mediates the mechanical stress-induced contraction in the dermal equivalent.
  • Findings provide insight into the biomechanical basis of wrinkle formation.