Ex vivo Human Skin Models for the Preclinical Assessment of Wound Healing and Antimicrobial Efficacy of Topical Treatments

Aim: Various tests have been developed to test the efficacy and potential toxicity of topically applied drugs. In vitro cell assays are used to screen drug efficacy on selected cell types, while reconstructed human skin is used as alternative to animal tests for acute skin toxicity. Ex vivo skin models allow the direct topical application of medical devices, contain immunologically active skin cells and appendages like hair follicles. Thus, we aimed at establishing chronic wound models using ex vivo human skin. Method: Skin is cultured in trans-well set-up at the air-liquid interface. Standardized wounds are created by abrasion, heating or punching. Wounds can be inoculated with bacteria to reproduce specific features of infection or be cultured for up to 12 days to follow the wound healing process. Such models have been used to test new therapeutic approaches such as antimicrobial wound dressings and exosomes derived from adult stem cells. Results / Discussion: Ex vivo human wound models have been developed in which bacteria such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus can grow as a biofilm. These models have been used to test the efficacy of antimicrobial-loaded dressings as well as local toxicity. To assess the wound healing properties of exosomes and conditioned medium from adipose tissue derived stem cells, ex vivo skin was cultured for 12 days and re-epithelialization, revascularization and inflammatory processes were monitored over time. Conclusion: Ex vivo wound models are valuable alternatives to animal testing for the preclinical evaluation of topical wound treatments.