Human skin-on-chip atopic dermatitis model for biomarker identification and therapeutic evaluation

Summary: Atopic dermatitis (AD) is a complex inflammatory skin disease affecting a large subset of the population (7.3% US adults). Current therapies have limited efficacy, highlighting the need for innovative human models, such as microfluidic devices, to uncover new therapeutic approaches and better understand the disease. In this study, skin biopsies from patient-matched lesional and non-lesional skin obtained from patients diagnosed with mild to moderate to severe AD were cultured in microfluidic devices. Subsequently, conditioned media was collected to identify AD-specific inflammatory biomarkers through secretome analysis. Additional AD hallmarks were evaluated <i>in vivo</i> through skin health assessments such as skin hydration, pH, and trans-epidermal water loss (TEWL), as well as <i>in vitro</i> through histological and immunofluorescence analysis to assess epidermal morphology and local inflammation. This prototype skin-on-chip model maintained its viability for up to 7 days while preserving the epidermal structure. Patient-matched lesional and non-lesional skin fragments showed immune infiltration in lesional skin, consistent with AD. Analysis of conditioned media at day 3 of culture revealed differential secretion of local inflammatory biomarkers, such as IL33, TNF-α, and TSLP, associated with AD and atopy-related pathways. These biomarkers were then correlated with systemic secretome from whole blood to distinguish local and systemic AD inflammatory signature. In conclusion, this human skin-on-chip approach offers new insights into the AD pathogenesis. Beyond identifying biomarkers, we envision using this device for targeting AD therapies and deeper understanding of the disease. Rafaela Mayumi Simoes Torigoe^{1, 2}, Bengisu Ozarslan Ercis², Jose M. de Hoyos Vega¹, Alan Gonzalez Suarez¹, Hemanth Gudapati², Gulnaz Stybayeva¹, Alexander Revzin¹, Saranya Wyles^{2, 3} 1. Physiology and Biomedical Engineering, Mayo Clinic Minnesota, Rochester, MN, United States. 2. Dermatology, Mayo Clinic Minnesota, Rochester, MN, United States. 3. Center for Regenerative Biotherapeutics, Mayo Clinic Minnesota, Rochester, MN, United States. Translational Studies: Cell and Molecular Biology