Hair follicle organoids: advances in construction, applications, and translational challenges

Hair follicles (HFs) are complex mini-organs characterized by a highly organized structure and cyclic regeneration. In recent years, hair follicle organoids (HFOs) have emerged as promising three-dimensional in vitro models that partially recapitulate the architecture and function of native hair follicles, providing new opportunities for studying hair biology and related disorders. This review first outlines the key biological features of HFs and highlights the essential role of epithelial-mesenchymal interactions in folliculogenesis, which serve as the foundation for organoid construction. We then summarize the fundamental principles of organoid technology and systematically compare current strategies for HFO generation, including primary cell-based co-culture systems and induced pluripotent stem cell (iPSC)-derived approaches, with an emphasis on their advantages and limitations. Furthermore, we discuss the applications of HFOs in disease modeling, drug screening, and regenerative medicine, while critically addressing current challenges such as difficulties in large-scale cultivation, limited maturity, and lack of standardization. Overall, HFOs represent a promising platform bridging basic research and clinical translation. Future efforts integrating biomaterials, microfluidic systems, and bioengineering technologies are expected to enhance their physiological relevance and accelerate their translational potential.