Personalized Models of Biological Barriers and Their Diseases: Recent Progress with Organs-On-Chips

Barrier tissues-epithelial and endothelial interfaces that compartmentalize the human body-govern molecular exchange, immune surveillance, and organ homeostasis. Their dysfunction is central to disorders ranging from dermatitis to neurodegeneration. Conventional static cultures fail to capture the relevant microenvironment and typically rely on cell lines that overlook patient-specific genetics. Organs-on-chips (OoCs), by contrast, can recapitulate barrier-specific flow, biomechanics, chemical gradients, and a multicellular architecture. Additionally, incorporating primary or induced pluripotent stem cell (iPSC)-derived cells into OoCs can open new avenues for precision medicine. This review surveys the architectural diversity and physiological functions of human barrier systems and explores how OoC platforms-especially those using patient-derived cells-are advancing barrier disease modeling. It reveals similar core features but also unique barrier characteristics requiring specific adaptations, resulting in varied progress across systems, and continued refinement of iPSC differentiation protocols and OoC engineering is needed overall. Nevertheless, existing biological and technological advances already offer substantial, untapped opportunities to create physiologically relevant, patient-specific disease models and drug-testing platforms, bridging the gap between fundamental biology and translational medicine.