Adapted from (Löwa et al., 2018).
According to the type of layer from the human skin that each model can mimic, two main types of reconstructed skin models are described: reconstructed human epidermis (RHE) models which mimic the epidermis and the living skin equivalents (LSEs) which aim to simulate the full human skin (Kuchler et al., 2013, Flaten et al., 2015, Randall et al., 2018). Nowadays, there are some commercially available models of the human epidermis (EpiSkin®, EpiDerm®, SkinEthic®) or full thickness skin (Phenion®) (Van Gele et al., 2011, Netzlaff et al., 2005).
The construction of the more complex 3D models usually include fibroblasts cultures which are embedded in a 3D matrix to mimic the dermis layer; then, keratinocytes can be seeded on top of the latter layer to simulate the epidermis. An air-liquid interface is established in order to allow the differentiation keratinocytes and formation of the different epidermal sublayers. The artificial matrix may include in their composition collagen or fibrin fibbers or even alginate and chitosan or different synthetic polymers (reviewed in (Sarkiri et al., 2019, Yu et al., 2019)).
Skin engineered substitutes may be used not only as alternatives toex vivo and in vitro non-cell-based models for testing drugs in healthy or pathological conditions but they can also be applied in patients for regeneration of damaged skin (reviewed in (Yu et al., 2019)). A diagram summarizing the different applications of skin engineered substitutes is depicted in Figure 4.