Skin Organoids for Disease Modelling, Drug Screening and Regenerative Medicine: Recent Advances and Future Perspectives.

Skin organoids are 3D multicellular systems formed through self-organisation in vitro, driving research toward functional-related phenotypic replication from structural mimicry to functionally relevant phenotypic replication. However, this field still faces challenges in improving vascularisation, neurogenesis, and immune integration. This review provides a comprehensive overview of the latest advancements in this field. First, it organises the construction of epidermis-dermis-basement membrane units, vascular/neural/immune modules and accessory organs such as hair follicles, sweat glands, and sebaceous glands into 'component-source-function readout' to highlight key points and clinically relevant endpoints (barrier function, hair growth, sweat gland secretion, and sensation). Subsequently, it outlines the key culture and assembly elements (extracellular matrix composition and mechanics, air-liquid interface, perfusion/organ-on-a-chip and bioprinting) that influence the maturation trajectory of tissues. Then, it compares the differences in plasticity, maturity and accessibility between pluripotent stem cells, adult/primary cells and patient-derived cells. At the application level, it concludes that skin organoids have been used to model inflammation, genetic disorders, infections, and tumours, enabling simultaneous efficacy and safety readouts in drug discovery and toxicology assessment. Translation challenges include vascularisation and perfusion, neurogenesis and sensory function, immune integration, batch consistency and GMP quality, scalability and cost. We propose a staged validation pathway integrating engineering, biology and regulatory considerations, and envision optimisations combining multi-omics, chemoproteomics and artificial intelligence to accelerate the transition from research-grade prototypes to clinical applications.