Three-dimensional models of human skin for biomedical applications

Artificial skin models have been replacing animal models in drug and cosmetics testing before proceeding to human trials. These models have been proven useful in preliminary screening and provide important insights. However, these models are limited as they do not replicate the complex architecture and microenvironment of human skin. This gap is now being filled by three-dimensional (3D) skin-models, which offer more accurate skin physiology and pathology. Recent advances in bioengineering techniques have enabled the creation of various 3D skin-models with unique characteristics and functions. This paper reviews recent advances in the field of 3D skin models. The paper considers different designs for creating these models, as well as fabrication techniques of scaffolding materials such as the addition of hydrogels, bioprinting, or electrospinning. The scaffold types enable corresponding mechanobiological properties of these skin models. Implementing these techniques with a suitable combination of cells creates skin models such as full-thickness models, epidermal models, melanoma models, or vascularized models. Each model has distinct advantages and limitations, including the use for scaffolding and challenges in developing organoids and organ-on-a-chip systems, as discussed in this review.