Open-source human skin model with an in vivo-like barrier for drug testing

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Patrícia Zoio
Sara Lopes-Ventura
Joana Marto
Abel Oliva

Abstract

There is a global trend towards the development of physiologically relevant in vitro skin models to reduce or replace animal testing in the evaluation of therapeutic drug candidates. However, only commercial reconstructed human epidermis models (RHEms) have undergone formal validation. Although these commercial models are suitable for a wide range of applications, they are costly, lack flexibility, and the protocols used to generate them are not transparent. In this study, we present an open-source full-thickness skin model (FTSm) and assess its potential for drug testing. The FTSms were developed using endogenous extracellular matrix to recreate the dermal compartment, avoiding animal-derived hydrogels. An RHEm based on an open-source protocol was also evaluated in parallel. The integrity of the skin barrier was analysed by challenging the surface with detergents and measuring cell viability as well as through trans-epithelial electrical resistance (TEER) measurements. Skin irritation studies were performed based on OECD guidelines and complemented with an evaluation of the impact on the skin barrier using TEER. The comparative permeation study of the developed models and a commercial membrane (Strat-M®) was performed using Franz diffusion cells and an infinite dose approach. The FTSm demonstrated structural and barrier properties comparable to the native human skin. Although the RHEm showed an overall better performance during drug testing, the FTSm presented better barrier properties than commercial models reported in the literature. These skin models can be a valuable contribution to accelerating the development and dissemination of alternatives to animal testing, circumventing the limitations of commercial models.

Article Details

How to Cite
Zoio, P., Lopes-Ventura, S., Marto, J. . and Oliva, A. (2022) “Open-source human skin model with an in vivo-like barrier for drug testing”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2111182.
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