Abstract: The present invention relates to silk fibroin bioinks specifically formulated for use in 3D bioprinting and the production of ex-vivo models capable of supporting hematopoiesis and the production of platelets and blood cells.

Abstract: The present invention provides, among other things, methods for producing platelets including the steps of providing a silk membrane about 2 ?m and 100 ?m thick, inclusive, contacting the silk membrane with a porogen to form a porous silk membrane comprising at least one silk wall defining a lumen, associating the porous silk membrane with stromal derived factor-1? and at least one functionalizing agent, forming a three dimensional silk matrix comprising interconnected pores wherein the pores have a diameter of between about 5 and 500 ?m, inclusive, wherein the silk matrix is formed around at least a portion of the porous silk membrane, introducing a plurality of megakaryocytes to the silk matrix such that the megakaryocytes are located at least partially within the porous silk matrix, and stimulating the plurality of megakaryocytes to produce platelets. Also provided are various new compositions and methods of making those compositions.

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.

Abstract: The present invention provides, among other things, methods for producing platelets including the steps of providing a silk membrane about 2 ?m and 100 ?m thick, inclusive, contacting the silk membrane with a porogen to form a porous silk membrane comprising at least one silk wall defining a lumen, associating the porous silk membrane with stromal derived factor-1? and at least one functionalizing agent, forming a three dimensional silk matrix comprising interconnected pores wherein the pores have a diameter of between about 5 and 500 ?m, inclusive, wherein the silk matrix is formed around at least a portion of the porous silk membrane, introducing a plurality of megakaryocytes to the silk matrix such that the megakaryocytes are located at least partially within the porous silk matrix, and stimulating the plurality of megakaryocytes to produce platelets. Also provided are various new compositions and methods of making those compositions.

Abstract: The present disclosure relates generally to silk fibroin and unlysed platelet compositions. The compositions are useful for a variety of medical uses such as wound healing or repair and soft tissue repair or augmentation.