A Dermis-on-a-Chip Model for Compound Screening

Dermal fibrosis is a significant barrier to effective wound healing, with excessive myofibroblast activation and extracellular matrix deposition leading to scar formation and compromised tissue function. Current in vitro models for studying dermal fibrosis, such as monolayer cultures and human skin equivalents (HSEs), have limited physiological relevance or scalability for drug screening. Here, we present a dermis-on-a-chip platform to enable screening of anti-fibrotic compounds in physiologically-relevant 3D dermal microtissues. Upon treatment with transforming growth factor beta (TGFß), the tissues exhibited hallmarks of fibrosis, including impaired integrity, increased tensile forces, altered cellular morphology, and a pro-fibrotic cytokine profile. Conversely, incorporation of QHREDGS (Q-peptide), an angiopoietin-1 derived peptide with known regenerative properties, selectively modulated these fibrotic changes. Q-peptide was found to reduce TGFß-induced tensile forces, suppress smooth muscle actin (SMA) expression, and upregulate certain cytokines associated with wound repair. Overall, these findings demonstrate the utility of dermis-on-a-chip model in compound screening. Overall design: RNAseq profile of dermal microtissues cultured with or without transforming growth factor beta (TGFb), in the presence or in the absence of QHREDGS-peptide (Q-peptide), an angiopoietin-1 derived peptide with known wound healing properties, after two days of culture.