Skin-on-a-chip technologies towards clinical translation and commercialization.

Skin is the largest organ of the human body which plays a critical role in thermoregulation, metabolism (e.g. synthesis of vitamin D), and protection of other organs from environmental threats, such as infections, microorganisms, ultraviolet radiation, and physical damage. Even though skin diseases are considered to be less fatal, the ubiquity of skin diseases and irritation caused by them highlights the importance of skin studies. Furthermore, skin is a promising means for transdermal drug delivery, which requires a thorough understanding of human skin structure. Current animal andtwo/three-dimensional skin models provide a platform for disease studies and drug testing, whereas they face challenges in the complete recapitulation of the dynamic and complex structure of actual skin tissue. One of the most effective methods for testing pharmaceuticals and modeling skin diseases are skin-on-a-chip (SoC) platforms. SoC technologies provide a non-invasive approach for examining 3D skin layers and artificially creating disease models in order to develop diagnostic or therapeutic methods. In addition, SoC models enable dynamic perfusion of culture medium with nutrients and facilitate the continuous removal of cellular waste to further mimic thecondition. Here, the article reviews the most recent advances in the design and applications of SoC platforms for disease modeling as well as the analysis of drugs and cosmetics. By examining the contributions of different patents to the physiological relevance of skin models, the review underscores the significant shift towards more ethical and efficient alternatives to animal testing. Furthermore, it explores the market dynamics ofskin models and organ-on-a-chip platforms, discussing the impact of legislative changes and market demand on the development and adoption of these advanced research tools. This article also identifies the existing obstacles that hinder the advancement of SoC platforms, proposing directions for future improvements, particularly focusing on the journey towards clinical adoption.