Developing a melanoma-skin-on-a-chip integrated with vasculature using an edgeless skin reconstruction approach.

Melanoma is the most aggressive form of skin cancer, characterized by high metastatic potential and frequent resistance to targeted therapies. Traditional 2D cultures and animal models often fail to accurately mimic the complexity of the human tumor microenvironment (TME). To improve the recapitulation of the cellular and mechanical microenvironmental cues, we bioengineered a melanoma-skin-on-a-chip platform using an edgeless 3D skin reconstruction strategy, which allows for creating mechanically relevant skin microenvironments. The platform integrates a dermis compartment made of primary dermal fibroblasts, human umbilical vein endothelial cells (HUVECs), and melanoma spheroids (generated using MeWo and A375 cell lines), and an epidermis compartment made of differentiated layers of primary keratinocytes. Melanoma spheroids consist of a mixture of melanoma cells, fibroblasts and endothelial cells in collagen droplets, and when incorporated into the engineered dermis, form morphologically heterogeneous structures that mimicked