Spheroid-based skin-on-a-chip platform for the evaluation of the toxicity of small molecules and nanoparticles

Abstract

Exposure of human skin to chemical agents may lead to skin sensitization, irritation, and corrosion. Time-efficient toxicity screening can be achieved using in vitro skin-on-a-chip models, however, currently used models either lack a multilayer structure characteristic of the skin or require long fabrication time. Here, we report the development and proof of concept of the application of the microfluidic spheroid-based skin-on-a-chip platform utilizing large arrays of multilayered skin spheroids (MSSs) and gravity-driven flow. The MSSs containing human dermal fibroblasts in the core and keratinocytes in the shell replicated the dermal and epidermal layers of skin, respectively. Within 3 days, the toxicity of five distinct small molecules was characterized by measuring their IC50 values, which enabled the differentiation of non-irritant chemical agents from the irritant ones and correlated with available in vivo scores for skin irritation. Toxicity screening was extended to carbon nanoparticles (carbon dots), liposomes, and metaflumizone insecticide encapsulated in the liposomes. This MSS-based skin-on-a-chip microfluidic platform for the safety evaluation of small molecules and nanoparticles has multiple applications in the cosmetic, pharmaceutical, and agriculture, and skincare fields.