Bioengineering of a full-thickness skin equivalent in a 96-well insert format for substance permeation studies and organ-on-a-chip applications

The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still the standard method for substance testing, although they are currently controversially discussed Therefore, the multi-organ chip is an attractive alternative to replace animal testing. The two-organ chip is designed to hold 96-well cell culture inserts (CCIs). Small-sized skin equivalents are needed for this. In this study, full-thickness skin equivalents (ftSEs) were generated successfully inside 96-well CCIs. These skin equivalents developed with in vivo-like histological architecture, with normal differentiation marker expressions and proliferation rates. The 96-well CCI-based ftSEs were successfully integrated into the two-organ chip. The permeation of fluorescein sodium salt through the ftSEs was monitored during the culture. The results show a decreasing value for the permeation over time, which seems a promising method to track the development of the ftSEs. Additionally, the permeation was implemented in a computational fluid dynamics simulation, as a tool to predict results in long-term experiments. The advantage of these ftSEs is the reduced need for cells and substances, which makes them more suitable for high throughput assays.

Subjects

full thickness skin equivalents

multi-organ chip

substance permeation

96-well cell culture insert

DDC Class

540: Chemie

570: Biowissenschaften, Biologie

610: Medizin

More Funding Information

Deutsche Forschungsgesellschaft (DFG) under grant No. PO413/12-1 and LA 1028/7-1

Lizenz

https://creativecommons.org/licenses/by/4.0/

Name

bioengineering-05-00043.pdf

Size

6.05 MB

Format

Adobe PDF

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Bioengineering of a full-thickness skin equivalent in a 96-well insert format for substance permeation studies and organ-on-a-chip applications