The use of three-dimensional (3D) cultures may induce cardiac progenitor cells to synthesize their
own extracellular matrix (ECM) and sarcomeric proteins to initiate cardiac differentiation. 3D
cultures grown on synthetic scaffolds may favour the implantation and survival of stem cells for cell
therapy when pharmacological therapies are not efficient in curing cardiovascular diseases and when
organ transplantation remains the only treatment able to rescue the patient’s life. Silk fibroin-based
scaffolds may be used to increase cell affinity to biomaterials and may be chemically modified to
improve cell adhesion. In the present study, porous, partially orientated and electrospun nanometric
nets were used. Cardiac progenitor cells isolated from adult rats were seeded by capillarity in the 3D
structures and cultured inside inserts for 21 days. Under this condition, the cells expressed a high
level of sarcomeric and cardiac proteins and synthesized a great quantity of ECM. In particular,
partially orientated scaffolds induced the synthesis of titin, which is a fundamental protein in
sarcomere assembly