Platelets are specialized cells produced by megakaryocytes in the bone marrow that represent the first defense against hemorrhage, yet they also play a pathological role in thrombosis, inflammation, and cancer. Millions of platelet transfusions are conducted each year, and the supply of this blood component is limited. There are many diseases where platelet production or function is impaired with severe consequences for patients. With such clinical need, new insight into the formation of platelets would have a major impact on patients and healthcare. We developed an innovative 3D system to study platelet production that represents the first spatial reconstruction of the bone marrow environment. In this system human megakaryocytes were able to migrate toward the vascular niche, extend proplatelets, and release functional platelets into vascular tubes. The combination of different bone marrow components and the compliance of silk-based vascular tubes makes this model a unique tool for the study of platelet formation and production for use in healthcare needs.