Skin-on-chip: Quo vadis?

There is a need for reconstructing the structural and functional complexity of human tissues such as skin to replace the animal models and provide accurate knowledge while solving ethical challenges in human medicine. Lately, microfluidics and tissue engineering have significantly advanced the development of 3D cell cultures and skin-on-chip (SoC), thus offering a cost-effective alternative to the generally used preclinical drug screening, toxicology applications, and cosmetic testing models. The current work presents a critical view on the SoC, from the fundamental concepts to the fabrication, applications, and commercialization. It comprehensively discusses the challenges faced by the 3D skin models and the perspectives of microphysiological skin platforms for preclinical pharmaceuticals and cosmeceuticals screening and disease research. It also highlights the technical and ethical requirements for successful SoC as physiological and pathological models applicable to personalized medicine. The SoC clinical and commercial translation depends on developing convergent biomanufacturing strategies and infrastructure focused on applications such as personalized skin disease models, skin grafts, and drug or cosmetics screening platforms.