Three-Dimensional Human Skin Models for Translational Dermatology: Current Platforms, Applications, and Open Questions

Human skin remains difficult to model in vitro because it brings together stratified epidermal, dermal, hypodermal, vascular, immune, appendageal, neural, and microbial elements within a single tissue. Traditional two-dimensional cultures and animal models still offer useful insight, but both have clear translational limits. Three-dimensional (3D) human skin models have therefore become increasingly valuable for mechanistic, pharmacologic, and regenerative research. This narrative review followed a fit-for-purpose literature selection framework. Priority was given to primary studies and reviews published between 2019 and 2025 that reported major advances in model architecture, biomaterials, vascularization, immune integration, appendage formation, sensorization, or translational application. Greater weight was given to studies that linked added complexity to measurable functional outputs. Current platforms include organotypic human skin equivalents, bioprinted constructs, microfluidic skin-on-a-chip systems, and pluripotent stem cell-derived organoids. Important advances include self-assembled or decellularized matrices that more closely reflect native extracellular matrix composition, perfusable microvasculature, hypodermal incorporation, immune cell integration, and real time sensing. These systems now support work in barrier testing, safety testing, dermal drug development, inflammatory dermatoses, melanoma, wound healing, aging, and regenerative transplantation. No single platform fully reproduces native human skin. The more relevant question is not how much complexity can be added, but which added features meaningfully improve performance for a defined endpoint. A fit-for-purpose framework may offer a better basis for model selection, benchmarking, standardization, and translational adoption. Future progress will depend on application specific validation, clearer performance benchmarks, scalable manufacturing, and closer alignment with regulatory and clinical needs. From that perspective, 3D skin models are best understood as complementary platforms for translational dermatology research.