An Innovative Fluid Dynamic System to Model Inflammation in Human Skin Explants

Abstract

Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics.

Recreating Human Skin In Vitro: Should the Microbiota Be Taken into Account?

“…Other ex vivo-based models have also been developed that aim to reproduce the pathophysiological conditions of inflammation in explanted human skin [112,113]. Recently, our research group [113] proved the ability of an innovative fluid dynamic system to preserve human skin explants: this preservation device allowed better results if compared with the classic static preservation protocols, and it was possible to induce an inflammatory phenotype in these preserved skin explants through the administration of substance P and dithranol.…”

“…Although they preserve the original 3D structure and contain all the constituents of human skin in vivo, even these systems are affected by some drawbacks: ethical permission is needed for sampling and processing, the biopsies may suffer from inter-and intra-sample variability, and the structural/functional preservation is limited in time [113].…”