Human skin models are widely accepted for studying skin biology and for the evaluation of dermatological products. These models include organotypic systems reconstructed from human cells and systems based on discarded surgical tissue. Cell-based systems are unable to fully recapitulate the differentiated architecture of skin, specifically the barrier function of the stratum corneum and the complex extracellular matrix of the dermis, while traditional full-thickness skin models, though encompassing a complete architecture, lose the ability to respond to various exogenous stimuli within hours. To address this unmet need, we have developed an explant system in which skin is cultured at an optimised tension. This system allows use of human skin without significant loss of viability, and maintains the physiological complexity and structural integrity of the skin as demonstrated in a variety of assays. i) In a wounding assay, the tension model demonstrated keratin 17 upregulation post-wounding similar to in vivo human skin, while untensioned models showed no observable upregulation. ii) In response to compounds with known activity in skin (e.g., NRF2 activator), the tension model responded as expected, while the other models showed little to no response. iii) Tensioned skin also retained resident dendritic cells, i.e., Langerhans cells (LCs), much longer than skin cultured without tension, allowing for toxicity studies previously only possible in live animals. With a growing demand for ex vivo skin models with regards to safety and efficacy assessment for products developed by the pharmaceutical and cosmetic industry, together with the demand to reduce animal testing, this model has the potential to play an important role in the future of investigative dermatology and drug discovery.
Conneely, M.J. et al.
Journal of Investigative Dermatology, Volume 138, Issue 5, S84
