Reconstructed human skin models have now been available for several decades. They use tissue engineering technology to recreate human skin in the laboratory, closely mimicking both structure and function of the skin in vivo. Much has been learned along the way about the optimal conditions required to create the most physiologically relevant models.
A matrix or scaffold is quite literally the foundation of success and must represent key extracellular matrix proteins found in the dermis and basement membrane. In some cases, synthetic biomaterials have been successful, circumventing the need for animal or human derived components and supporting a more standardised and reproducible system.
Human epidermal keratinocytes are seeded onto the support and, once the basal layer has formed, the models are exposed to the air-liquid interface for up to 28 days to generate a multi-layered, fully differentiated human epidermis. The composition of the culture medium is key to success and modulating the calcium level is essential due to its central role in keratinocyte differentiation and signalling pathways. The gene expression in each cell layer, along with cell-cell and cell-matrix interactions, closely resemble in vivo human skin.
Crucially, reconstructed skin models have a barrier function – a key advantage when dosing ingredients and formulations onto the surface of the models to assess a variety of safety and efficacy endpoints. However, the barrier tends to be thinner than in epidermis in vivo, with the thickness and lipid composition variable between different commercially available models. Differences such as this can result in over-predicting the toxicity of chemicals. From a safety standpoint, this may be considered acceptable, but from a commercial viewpoint, companies may encounter false positive results for endpoints such as skin irritation, with important implications for innovation and product development.
Recently, responses to chemicals have been compared between reconstructed skin models and human volunteer patch tests, to create sensitive prediction models for today’s ultra-mild cosmetics and personal care products. More sophisticated methods have evolved over time, using the models for a wider variety of safety and efficacy endpoints. These range from skin sensitisation, genotoxicity and phototoxicity tests, to methods generating claim support data for cosmetic efficacy, such as healthy aging and antioxidant activity.
Reconstructed skin models are now available in more formats, including models derived from donors of different ages and from a variety of global regions, supporting the increasing demand for product development taking diversity and inclusion into account. It is also possible to simulate disease states such as psoriasis to support drug candidate screening and preclinical development.
With an increasing demand for ethical, cruelty-free and vegan products worldwide, recent adaptations of tests to completely animal-free conditions and vegan accreditation of some reconstructed skin models ensures that the technology meets not only the scientific needs of the industry but also the ethical demands of today’s consumers.
Many of the available tests are accepted at OECD level and are therefore used to generate safety data for global regulators, playing an important role in the replacement of animal testing with more human-relevant science.
A matrix or scaffold is quite literally the foundation of success and must represent key extracellular matrix proteins found in the dermis and basement membrane. In some cases, synthetic biomaterials have been successful, circumventing the need for animal or human derived components and supporting a more standardised and reproducible system.
Human epidermal keratinocytes are seeded onto the support and, once the basal layer has formed, the models are exposed to the air-liquid interface for up to 28 days to generate a multi-layered, fully differentiated human epidermis. The composition of the culture medium is key to success and modulating the calcium level is essential due to its central role in keratinocyte differentiation and signalling pathways. The gene expression in each cell layer, along with cell-cell and cell-matrix interactions, closely resemble in vivo human skin.
Crucially, reconstructed skin models have a barrier function – a key advantage when dosing ingredients and formulations onto the surface of the models to assess a variety of safety and efficacy endpoints. However, the barrier tends to be thinner than in epidermis in vivo, with the thickness and lipid composition variable between different commercially available models. Differences such as this can result in over-predicting the toxicity of chemicals. From a safety standpoint, this may be considered acceptable, but from a commercial viewpoint, companies may encounter false positive results for endpoints such as skin irritation, with important implications for innovation and product development.
Recently, responses to chemicals have been compared between reconstructed skin models and human volunteer patch tests, to create sensitive prediction models for today’s ultra-mild cosmetics and personal care products. More sophisticated methods have evolved over time, using the models for a wider variety of safety and efficacy endpoints. These range from skin sensitisation, genotoxicity and phototoxicity tests, to methods generating claim support data for cosmetic efficacy, such as healthy aging and antioxidant activity.
Reconstructed skin models are now available in more formats, including models derived from donors of different ages and from a variety of global regions, supporting the increasing demand for product development taking diversity and inclusion into account. It is also possible to simulate disease states such as psoriasis to support drug candidate screening and preclinical development.
With an increasing demand for ethical, cruelty-free and vegan products worldwide, recent adaptations of tests to completely animal-free conditions and vegan accreditation of some reconstructed skin models ensures that the technology meets not only the scientific needs of the industry but also the ethical demands of today’s consumers.
Many of the available tests are accepted at OECD level and are therefore used to generate safety data for global regulators, playing an important role in the replacement of animal testing with more human-relevant science.
