Enhanced predictive capacity using dual-parameter chip model that simulates physiological skin irritation.

Current alternatives to animal testing methods for skin irritation evaluation such as reconstructed human epidermis models are not fully representing physiological response caused by skin irritants. Skin irritation is physiologically induced by the dilation and increased permeability of endothelial cells. Thus, our objectives were to mimic physiological skin irritation using a skin-on-a-chip model and compare predictive capacities with a reconstructed human epidermis model to evaluate its effectiveness. To achieve our goals, the skin-on-a-chip model, consisting of three layers representing the epidermal, dermal and endothelial components, was adapted. Cell viability was measured using the OECD TG 439 protocol for test substance evaluation. The tight junctions of endothelial cells were also observed and measured to assess physiological responses to test substances. These parameters were used to physiologically evaluate cell-to-cell interactions induced by test substances and quantify model accuracy, sensitivity, and specificity. Based on in vivo data, the classification accuracy of twenty test substances using a dual-parameter chip model was 80%, which is higher than other methods. Besides, the chip model was more suitable for simulating human skin irritation. Therefore, it is important to note that the dual-parameter chip model possesses an enhanced predictive capacity and could serve as an alternative to animal testing for skin irritation.