Engineering a human skin equivalent to study dermis remodelling and epidermis senescence in vitro after UVA exposure

Abstract

Utra Violet type A (UVA) exposure strongly affects the ageing of human skin by modifying both epidermis and dermis and their cross talk as well. The possibility to get a deep understanding in vitro of such crucial mechanism would have a huge impact in the development of antiageing compounds. Here, we present a full thickness model of human skin equivalent formed by a millimeter-sized dermis completely composed of fibroblasts embedded in their own extracellular matrix. We show that such endogenous nature of the dermis compartment allows the replication of the complexity of the mutual interactions occurring between cellular and extracellular components of the skin under UVA exposure: (a) oxidative stress formation in the whole tissue (dermis and epidermis); (b) senescence of germinative layer of epidermal tissue in terms of p63, ki67, and activated caspase-3 regulation; (c) modification of the collagenous network architecture in the dermis compartment. By using this human skin model, it is possible to study a widely shared assumptions not yet proved in vitro such the effect of UVA on the self-renewal capability of skin stem cells.

Advances in generation of three-dimensional skin equivalents: pre-clinical studies to clinical therapies

“…Natural biomaterials like collagen, chitosan, hyaluronic acid, gelatin and fibrin have been commonly used as scaffolds for the generation of skin equivalents. Casale et al [11] described a method in which human fibroblasts were cultured on gelatin microscaffolds in dynamic bioreactors until they formed human dermis equivalents composed of fibroblasts embedded in their own ECM. Epidermal cells were then cultured on the surface of the human dermis equivalent.…”

Occupational Exposure to Solar UV Radiation of a Group of Fishermen Working in the Italian North Adriatic Sea

“…Furthermore, UV exposure is responsible also for other skin diseases, such as actinic keratosis and photo-aging [1,6,7], and it is involved in the pathogenesis of several ocular disorders, such as cataract, pterygium, and possibly macular degeneration [6,7,8,9,10,11]. It has to be noted that not only high energetic UV-B rays are able to induce acute and chronic adverse effects, but also longer UV-A wavelengths, which are largely represented within the solar radiation reaching the Earth’s surface, have a great ability to photochemically interact with biological tissues, generating oxidative damages, and therefore playing a major role in photo-immunosuppression and cellular senescence, also after short-term exposures [2,12,13].…”

Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules

“…To assess the microneedles' ability to satisfy such requirements, a human skin equivalent (Endo-HSE) was used as assay platform. Endo-HES is a functional and histological competent tissue that captures several fundamental features of the native human skin (Casale et al, 2016, 2018). In addition, in contrast to the use of pig skin, Endo-HSE is of human origin and can reproduce the sample's thickness as well as ECM compactness, thus avoiding the variability correlated to the age and region of the animal.…”

“…Endogenous-Human Skin Equivalent (Endo-HSE) (Casale et al, 2016, 2018) was used as the assay platform to evaluate the diffusion profile of the oxidation product formed by the reaction of ABTS soaked in Endo-HSE with the Laccase encapsulated in the array of microneedles. Endo-HSE was soaked in the ABTS solution (11 mg/ml in sodium citrate) for 30 min at RT.…”