Advanced Online Monitoring of In Vitro Human 3D Full-Thickness Skin Equivalents

Abstract

Skin equivalents and skin explants are widely used for dermal penetration studies in the pharmacological development of drugs. Environmental parameters, such as the incubation and culture conditions affect cellular responses and thus the relevance of the experimental outcome. However, available systems such as the Franz diffusion chamber, only measure in the receiving culture medium, rather than assessing the actual conditions for cells in the tissue. We developed a sampling design that combines open flow microperfusion (OFM) sampling technology for continuous concentration measurements directly in the tissue with microfluidic biosensors for online monitoring of culture parameters. We tested our design with real-time measurements of oxygen, glucose, lactate, and pH in full-thickness skin equivalent and skin explants. Furthermore, we compared dermal penetration for acyclovir, lidocaine, and diclofenac in skin equivalents and skin explants. We observed differences in oxygen, glucose, and drug concentrations in skin equivalents compared to the respective culture medium and to skin explants.

Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover

“…As an alternative, biosensors offer direct and real-time detection of many biological and chemical substances with high specificity and sensitivity, small size, and cost-effectiveness [ 11 ]. Commercial, multiplexed biosensors are now available on the market and have previously been applied to monitor fermentation or skin explants [ 12 , 13 ]. Using biosensors offers clear advantages over other existing biometabolic analysis approaches, supporting the choice of an enzymatic biosensor for our metabolic study in this paper.…”