Advances in, and prospects of, 3D preclinical models for skin drug discovery
Mohammad Imran, Peter M. Moyle, Danielle Kamato, Yousuf Mohammed
Abstract
• The development of advanced 3D skin models improves the drug discovery process in the skin domain. • 3D skin models overcome the existing limitations of current 2D models. • 3D model advancements reduce the burden of animal experimentation. • Regulatory authorities such as US FDA, ANVISA, and TGA strongly encourage 3D models for the drug discovery process. The skin has an important role in regulating homeostasis and protecting the body from endogenous and exogenous microenvironments. Although 3D models for drug discovery have been extensively studied, there is a growing demand for more advanced 3D skin models to enhance skin research. The use of these advanced skin models holds promise across domains such as cosmetics, skin disease treatments, and toxicity testing of new therapeutics. Recent advances include the development of skin-on-a-chip, spheroids, reconstructed skin, organoids, and computational approaches, including quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) research. These innovations are bridging the gap between traditional 2D and advanced 3D models, moving progress from research to clinical applications. In this review, we highlight in vitro and computational skin models with advanced drug discovery for skin-related applications.