TY - JOUR

T1 - Advanced Online Monitoring of In Vitro Human 3D Full-Thickness Skin Equivalents

AU - Schaller-Ammann, Roland

AU - Kreß, Sebastian

AU - Feiel, Jürgen

AU - Schwagerle, Gerd

AU - Priedl, Joachim

AU - Birngruber, Thomas

AU - Kasper, Cornelia

AU - Egger, Dominik

N1 - Funding Information: Funding: This research was funded by Austrian Research Promotion Agency (FFG) grant number 859279.

PY - 2022/7/8

Y1 - 2022/7/8

N2 - 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.

AB - 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.

KW - full-thickness skin equivalent

KW - glucose

KW - lactate

KW - open flow microperfusion

KW - oxygen

KW - penetration tests

KW - pH

KW - pharmacokinetics

KW - sensors

KW - skin explants

UR - http://www.scopus.com/inward/record.url?scp=85134483762&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics14071436

DO - 10.3390/pharmaceutics14071436

M3 - Article

AN - SCOPUS:85134483762

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

IS - 7

M1 - 1436

ER -