Open-source human skin model with an in vivo-like barrier for drug testing.
ALTEX
; 39(3): 405418, 2022.
Article
en En
| MEDLINE
| ID: mdl-35319071
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 (RHEm) 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 FTSm was developed using endogenous extracellular matrix to recreate the dermal compartment, avoiding animal-derived hydrogels. An RHEm based on an open-source protocol was evaluated in parallel. The integrity of the skin barrier was analyzed by challenging the surface with detergents and measuring cell viability as well as by 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 by TEER measurement. The permeation of a dye through the developed models and a commercial membrane (Strat-M®) was compared using Franz diffusion cells and an infinite dose approach. The FTSm demonstrated structural and barrier properties comparable to native human skin. Although the RHEm showed a better performance in drug testing, the FTSm presented better barrier properties than commercial models as reported in the literature. These skin models can be a valuable contribution to accelerating the development and dissemination of alternatives to animal testing, avoiding the limitations of commercial models.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pruebas de Irritación de la Piel
/
Irritantes
Tipo de estudio:
Guideline
Límite:
Animals
/
Humans
Idioma:
En
Revista:
ALTEX
Asunto de la revista:
MEDICINA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Portugal