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Demonstration of the Rat Ischemic Skin Wound Model
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Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound-on-a-Chip Model.

Sahar Biglari1, Thi Y L Le1, Richard P Tan2

  • 1School of Chemical Biomolecular Engineering, University of Sydney, Sydney, 2006, Australia.

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|December 5, 2018
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Summary

This study presents a novel microfluidic wound-on-chip model to simulate early skin wound inflammation. The system effectively models paracrine signaling and allows for the testing of anti-inflammatory compounds.

Keywords:
drug screeninginflammationmicrofluidicsorgan-on-chipswound healing

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Area of Science:

  • Biomedical Engineering
  • Tissue Engineering
  • Microfluidics

Background:

  • Microfluidic systems are advancing the modeling of human skin and dermal wound healing.
  • Existing models often lack key elements for fully representing dermal wound healing processes.

Purpose of the Study:

  • To develop a cost-effective, multicellular microfluidic system to mimic the paracrine component of early wound inflammation.
  • To assess the utility of collagen and Matrigel for cell adhesion in the model.
  • To evaluate the system's potential for screening anti-inflammatory compounds.

Main Methods:

  • A three-channel microfluidic wound-on-chip model was designed.
  • Dermal fibroblasts and human umbilical vein endothelial cells (HUVECs) were cultured.
  • Inflammation was induced using tumor necrosis factor alpha (TNF-α) or co-culturing with macrophages (M1/M2).
  • Cytokine levels (IL-1β, IL-6, IL-8) and vascular structure formation were analyzed.
  • The effect of Dexamethasone as an anti-inflammatory agent was evaluated.

Main Results:

  • Both TNF-α induction and macrophage co-culture significantly increased cytokine levels.
  • M1 and M2 macrophages stimulated cytokine production and vascular structure formation, with M2 macrophages showing enhanced effects.
  • Dexamethasone treatment attenuated the increase in cytokine levels.
  • Collagen and Matrigel were successfully used for cell adhesion.

Conclusions:

  • The developed wound-on-chip system effectively models the paracrine signaling in early wound inflammation.
  • The system demonstrates potential for screening anti-inflammatory drugs.
  • The model provides a valuable tool for studying dermal wound healing mechanisms.