Biomimetic Mammary Gland Organoid-on-a-Chip for Producing Selected Human Milk Components

Milk is an essential nutritional source for human health, yet developing efficient and sustainable indoor dairy production systems to produce milk-associated components remains a major challenge. Here, we propose a biomimetic mammary gland-on-a-chip system that recapitulates both the structural features and lactation mechanism of the mammary gland for producing milk-associated bioactive components. The chip is designed with a medium channel providing circulation, an intermediate porous hydrogel layer for substance diffusion, and highly specialized microchambers for culturing mammary epithelial cells. The mammary gland-on-a-chip enables tight-junction formation and active secretion of milk bioactive components such as lactotransferrin and triglycerides. More importantly, by expanding the microchambers and parallelizing the chips, increased collection of partial milklike secretions containing selected bioactive components was achieved. Our work represents the successful development of a robust microphysiological system as a potential in vitro platform for mammary gland research and is promising in addressing future food and environmental crises.