Lei Li, Wenqi Si, Zhehu Jin, Wenyu Jin
Traditional two-dimensional (2D) cell cultures and animal models often fail to replicate the complex layered structure and pathological microenvironment of human skin. This paper systematically reviews the latest advancements in three-dimensional (3D) human skin model construction, specifically focusing on bioprinting, organoid, and organ-on-a-chip technologies. Our analysis highlights that the integration of vascularization, skin appendages, and multi-omics data represents the core advancements in enhancing physiological realism for simulating. Despite these strides, challenges such as a lack of standardization and high medical costs remain as barriers to clinical translation. We conclude that future directions must leverage interdisciplinary synergy-integrating artificial intelligence and personalized multi-omics-will be essential to transition 3D skin models from laboratory tools to precise clinical applications.