The Bioengineering of Microspheric Skin Organoids and Their Application in Drug Screening

It has been a challenge to develop skin models which exhibit the key characteristics of the human skin and facilitate high-throughput drug screening. In this study, a method is developed to construct microspheric skin organoids based on spinning bioreactors. The organoid consists of a core-shell structure to mimic the bilayered skin structure, where the shell is composed of cultured human keratinocytes, resembling the epidermis, and the core, which mimics the dermis, comprises human dermal fibroblasts and collagen. In fabrication of the organoid, the cores are cultured with keratinocytes in spinner flasks under defined conditions to facilitate epidermal growth and differentiation to form mature barrier. To enable efficient drug screening, the organoid is equipped with a luciferase reporter to detect canonical Wnt activation, and Minoxidil is identified to induce epidermal Wnt/beta-catenin pathway signaling. Thus, the study has developed a novel method for efficient preparation of uniform microspheric skin organoids with potential applications for high-throughput drug testing and screening.