Advances in engineered organoid models of skin for biomedical research

Abstract In recent years, significant progress has been made in the development of organoids, which offer promising opportunities for developmental and translational research. With advances in cell biology and bioengineering techniques, skin models are evolving from conventional multilayered structures to appendage-bearing spheroids or 3D biomimetic models. This comprehensive review aims to provide an in-depth understanding of organoid models of the skin, covering topics such as skin development, construction strategies and key elements, types of organoid models, biomedical applications, and challenges. Embryonic skin development is briefly introduced to provide a foundational understanding of construction principles. Current engineering strategies are outlined, highlighting key elements such as cell sources, bioengineering techniques, 3D scaffolds, and crucial signaling pathways. Furthermore, recent advances in generating organoids with structural and functional parallels to native skin are meticulously summarized. These developments facilitate the utilization of organoids in diverse applications, such as modeling skin disorders, developing regenerative solutions, and understanding skin development. Finally, the challenges and prospects in the field are discussed. The integration of state-of-the-art bioengineering techniques with a deep understanding of skin biology is promoting the production and biomedical application of these organoid models.