[Skin organoids: an emerging platform from three-dimensional construction to regenerative application]

Skin organoids are three-dimensional, self-organized in vitro models that recapitulate the architecture and function of skin tissue. This article comprehensively outlines the current progress and application prospects of skin organoids. Based on complexity, skin organoids can be classified into epidermal, appendage-specific, and full-thickness skin organoids. The construction of skin organoids highly depends on extracellular matrix capable of replicating tissue-specific microenvironment to provide essential physical scaffolding and biochemical cues. Construction strategies encompass natural/synthetic hydrogels scaffold and engineered approaches such as three-dimensional bioprinting, which provide tunable physicochemical and biological support. In terms of applications, skin organoids have been widely used to model physiological and pathological processes, including skin development, tumors, and infectious and inflammatory skin diseases, serving as valuable platforms for studying disease mechanisms and screening drug targets. In the field of wound repair, organoids not only serve as research models to uncover healing mechanisms, but also act as transplantable units that promote re-epithelialization, vascularization, and the regeneration of hair follicles and sweat glands, thereby achieving functional skin restoration. Although skin organoids are currently still facing challenges in terms of structural maturity, vascularization, recapitulation of the immune microenvironment, and heterogeneity, their potential in regenerative medicine, personalized therapy, and translational applications will continue to expand with the advances of technologies such as matrix biology, organ-on-a-chip systems, and automated culture.