In Vitro Skin Models for Skin Sensitisation: Challenges and Future Directions

Allergic contact dermatitis is one of the most common adverse events associated with cosmetic use. Accordingly, assessment of skin sensitisation hazard is required for safety evaluation of cosmetic ingredients. Urged by the European cosmetics legislation ban on animal testing, skin sensitisation has been an intense field in the past two decades, focused on transitioning to the use of alternative methods for hazard prediction. The first alternative methods accepted for regulatory use have been in place for almost a decade, but none as stand-alone replacement for the reference animal method, the murine Local Lymph Node Assay (LLNA). While their strengths and limitations are being evaluated, and the search for new combinations of the adopted methods and other sources of information increase confidence, novel methods based on reconstructed human epidermis (RHE) have recently been validated and joined the available methods. Their unique characteristics provide important advantages that will potentially enhance non-animal testing for skin sensitisation in cosmetics and related industries. In this review, we recapitulate how reconstructed human skin models have been used as platforms for skin sensitisation testing, including the latest approaches using organ-on-a-chip and microfluidic technologies, aimed to develop next-generation organotypic skin models with increased complexity and monitoring capabilities.