Abstract
Bioengineered skin constructs provide a physiologically relevant platform for fundamental and translational research. We have developed a complex, robust and reproducible full thickness skin equivalent, which has been validated against in vivo skin using in-depth analyses. To mimic the dermis in vitro, primary fibroblasts were cultured within the Alvetex® Scaffold to produce endogenous extracellular matrix proteins. The robust dermal compartment supports the generation of an organised, stratified and keratinised epidermis. Additional cell types have also been incorporated, such as melanocytes and immune cells, to increase the skin equivalent complexity. The human skin equivalent recapitulates the organised structure of human skin in vitro. Skin constructs that represent different ages have been developed using neonatal, young or ageing cells. The use of ageing and senescent cells recreates the ageing skin phenotype in vitro, with regards to epidermal thinning, decreased keratinocyte proliferation and reduced extracellular matrix synthesis. Pigmented skin equivalents include melanocytes, which localise to the basal layer and transfer melanin to neighbouring keratinocytes to form a protective supranuclear cap. The pigmented skin equivalents are functional, and exposure to ultraviolet radiation induces a tanning effect. Langerhans cells have also been incorporated into the epidermis to produce an immune-competent skin equivalent, which is responsive to topical allergens and irritants. We have developed advanced, robust and reproducible skin constructs that resemble the structure of human skin. These skin equivalents have multifaceted research applications such as investigating the underpinning mechanisms of skin ageing, assessing the effect of exogenous stressors and evaluating cosmetic formulations.
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