Recent advances in immunocompetent human skin-on-chip models: Construction strategies and biomedical applications

Human skin, as the body's largest organ and primary barrier, possesses a sophisticated immune microenvironment crucial for its defensive functions. Recent advancements in organ-on-a-chip technology have facilitated the development of biomimetic skin-on-chip models, especially in the accurate recapitulation of complex immune responses for human skin diseases. This review provides a comprehensive overview of the construction strategies and biomedical applications of immunocompetent human skin-on-chip models. We systematically detail the essential components for building these systems, encompassing cell sources, biomaterial matrices, and microfluidic fabrications. A major focus is placed on the strategic integration of key immune components, specifically immune cells such as Langerhans cells, T cells, and macrophages, as well as critical immune factors. These immunocompetent skin models serve as powerful platforms for disease modeling of inflammatory conditions like psoriasis, atopic dermatitis, and allergic contact dermatitis. Furthermore, we highlight their applications in drug development, toxicity testing, and cosmetic safety assessments. Finally, the future perspective and challenges underscoring the role of immunocompetent skin-on-chip technology in advancing precision medicine and dermatological research are discussed.