Engineering immune-competent hair follicle microphysiological systems: from organoid assembly to dynamic immune...

Hair follicle organoids (HF organoids) have progressed from simple epithelial-mesenchymal aggregates to spatially organized follicle-like structures and skin-hair follicle composite models. However, most current systems still focus on follicular morphogenesis and structural reconstruction, with limited capacity to recapitulate the immune, vascular, neural, and dynamic regulatory features of the native hair follicle (HF) microenvironment. This limitation is particularly relevant to immune-mediated hair disorders, such as alopecia areata, lichen planopilaris, and frontal fibrosing alopecia, in which immune privilege (IP) collapse, inflammatory infiltration, hair follicle stem cell (HFSC) niche damage, and tissue remodelling are central pathological events. In this Review, we discuss the transition from structurally oriented HF organoids towards immune-competent hair follicle microphysiological systems (HF-MPS). We summarize the structural basis of HF engineering, define immune competence as a functional state involving IP maintenance, immune-cell regulation of HF cycling and regeneration, and controllable inflammatory injury, and examine engineering strategies including local immune microenvironment control, compartmentalized culture, dynamic perfusion, vascularized and innervated interfaces, and quantitative monitoring. We further discuss applications in disease modelling, dynamic drug evaluation, patient-derived platforms, and regenerative medicine, while highlighting evidence boundaries and technical limitations. Immune-competent HF-MPS should be viewed as evolving human-relevant platforms rather than mature replacements for existing models.