Human-Relevant In Vitro Skin Models: From Regulatory-Validated Platforms to Emerging Technologies for Translational...

The rapid advancement of human-relevant in vitro skin models has been driven by increasingly stringent regulatory restrictions on animal testing and the growing recognition that conventional animal and two-dimensional cell culture systems fail to accurately predict human skin biology and clinical outcomes. Three-dimensional reconstructed human skin models, ex vivo human skin platforms, and next-generation bioengineered systems have been recognized as critical tools for dermatological research, cosmetic safety assessment, and pharmaceutical development. This review focuses on commercially available in vitro human skin models currently used in regulatory and research settings, as well as emerging technologies under active development. We provide an overview of reconstructed human epidermis and full-thickness skin equivalents, functional variants incorporating pigmentation and microbiome support, and ex vivo human skin models derived from surgical tissues. Additionally, we discuss cutting-edge platforms, including vascularized and perfused skin models, immune-competent skin constructs, organoid-based appendage-containing models, and microbiome-integrated platforms. Furthermore, we highlight current limitations, regulatory gaps, and future directions for standardization, scalability, and clinical translation. Collectively, advanced human skin models are expected to significantly enhance dermatological research by enabling predictive, ethical, and mechanistically informative testing strategies that bridge the gap between in vitro experimentation and clinical outcomes.