A dermis-on-a-chip model for compound screening

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Dermatology

Background:

• Dermal fibrosis impedes wound healing due to excessive myofibroblast activation and extracellular matrix deposition.
• Existing in vitro models like monolayer cultures and human skin equivalents (HSEs) lack physiological relevance and scalability for drug screening.
• Developing advanced models is crucial for understanding fibrosis and identifying effective anti-fibrotic therapies.

Purpose of the Study:

• To develop and validate a dermis-on-a-chip platform for studying dermal fibrosis.
• To assess the platform's utility in screening anti-fibrotic compounds.
• To investigate the effects of a regenerative peptide (Q-peptide) on fibrotic responses.

Main Methods:

• Fabrication of a 3D dermis-on-a-chip platform housing dermal microtissues.
• Induction of fibrotic hallmarks in microtissues using transforming growth factor beta (TGFβ).
• Treatment of fibrotic microtissues with Q-peptide and assessment of fibrotic markers.

Main Results:

• TGFβ treatment induced key fibrotic features: impaired integrity, increased tensile forces, altered cell morphology, and a pro-fibrotic cytokine profile.
• Q-peptide selectively mitigated TGFβ-induced fibrotic changes.
• Q-peptide reduced tensile forces, suppressed smooth muscle actin (SMA) expression, and modulated cytokine profiles.

Conclusions:

• The dermis-on-a-chip platform provides a physiologically relevant model for studying dermal fibrosis.
• This model is effective for screening anti-fibrotic compounds and understanding their mechanisms.
• Findings highlight the potential of Q-peptide in modulating fibrotic processes for enhanced wound repair.