233 A novel ex vivo skin culture device enables clinically representative skin testing

Dermatology has the poorest rate of successful bench-to-clinic transitions. In part this is due to safety testing being historically performed on unrepresentative animal models, or animal replacement tests that use animal, rather than human data as the benchmark for efficacy. As a result, preclinical models are unable to faithfully replicate human responses. Here, we examined whether a novel environmentally relevant skin culture device is able to better mimic human responses for skin permeation and irritation. We engineered a biphasic fluidic culture device combining regulation of atmospheric air, humidity, temperature, pH and media flow, replicating the physiological environment of human skin. Using this device, we assessed the permeation of caffeine and ibuprofen in ex vivo skin at baseline and in skin cultured for five days and found no significant difference in absorption profiles (p 0.05 ANOVA with Dunnet’s multiple comparisons test). Additionally, we assessed the skin irritation potential of compounds, developing methodology based on the approved OECD 439 skin irritation test. Approved validation chemicals, and compounds incorrectly categorised with approved models were assessed. The validation chemicals were correctly categorised (100% accuracy), and the results of the incorrectly categorised compounds fully replicated published human clinical data. In conclusion, physiologically relevant skin culture was essential for maintaining ex vivo skin function and clinically relevant skin responses. Using skin permeation and irritation as examples, we demonstrate this methodology should replace traditional culture methods for the development of accurate, human-representative preclinical analysis for confident bench-to-clinic transitions.