Guiding Skin Organoid Generation via Extracellular Matrix Cues and Spatially Controlled Morphogen Gradients

The study aimed to guide the self-organization and differentiation of induced pluripotent stem cells (iPSCs)-derived embryoid bodies (EBs) into anatomically-relevant skin organoids using extracellular matrix (ECM) cues and spatially-controlled morphogen gradients. The researchers evaluated the performance of chemically-defined hydrogels based on dermis-relevant ECM molecules. They found that collagen type I hydrogels supplemented with laminin and fibronectin promoted the growth and generation of skin organoids with significantly increased pigmentation and hair follicle generation. They also developed a 3D-bioprinted hydrogel-based microfluidic device that can create asymmetrical cross-gradients of differentiation factors. Under these gradients, the EBs showed spatial patterning via polarized differentiation into distinct skin cell lineages and appendages. The skin organoids adopted an elongated shape in the device, leading to the generation of mature skin organoids. This approach may have a transformative impact on our understanding of human skin morphogenesis and developmental skin diseases.