Abstract: Systems and methods for predicting patient-specific responses to the administration of medicaments that are indicated to modulate megakaryocyte differentiation, proplatelet formation, and/or platelet production are disclosed. The systems and methods can include a three-dimensional bone marrow model that is composed of silk fibroin sponges including a protein of the extracellular matrix, such as fibrinogen. The methods include creating patient-specific megakaryocyte progenitors (or progenitors thereof), seeding those progenitors into the model, introducing the medicament to the progenitors within one model, perfusing the model with a cell culture medium, maturing the progenitors, comparing platelet generation from the model including the medicament to a control model, and generating a report having a prediction of in vivo efficacy based on the comparison.