Advancing dermatology with skin equivalents and organoids in pathophysiology and drug testing

The progression of dermatologic models from simple two-dimensional cultures to advanced three-dimensional skin equivalents (SE) and skin organoids (SKO) has transformed skin research and therapy. This scoping review explores the evolution of SE, with a particular emphasis on human-induced pluripotent stem cells (hiPSCs)-derived SKO, and skin-on-chip as next-generation bioengineered platforms for disease modelling and drug discovery. We present a critical synthesis of current evidence on the development and applications of these models for recapitulating skin pathophysiology, testing therapeutic strategies, and identifying limitations of existing systems, thereby offering an evidence-based overview of existing knowledge in dermatology. This review highlights the application of such skin models across diverse fields, including aging, inflammatory and infectious diseases, radiation biology, pharmacology, and hair research. Together, recent advancements, including the incorporation of skin appendages, vascular, immune, and neural components into increasingly complex in vitro models, represent a path forward to enhance clinical relevance in dermatological research and therapy while simultaneously reducing reliance on animal models. STATEMENT OF SIGNIFICANCE: This study offers a comprehensive and timely analysis of the evolution of skin experimental models, such as skin equivalents and organoids, and their applications in dermatology. It helps dermatology researchers to assess the current limitation of skin models and identify future directions in skin model development.