Summary: One of the major challenges in cardiac cell therapy is cell death and low rate of cardiac differentiation. In this regard, a series of thermosensitive and injectable hydrogels with similar physicomechanical properties of cardiac tissue can be an ideal candidate for delivering human unrestricted somatic stem cells (hUSSCs) and improve the quality of cell therapy. Here, we designed N-isopropylacrylamide/acrylic acid/N-acryloxysuccinimide/2-hydroxyethyl methacrylate-poly lactide (NIPAAm/AAc/NAS/HEMAPLA) hydrogel via ring-opening polymerization for encapsulation of the cells. To improve biological activities, biomaterials like hyaluronic acid (HA), , (AV), and silk fibroin (SF) were added with pure hydrogel (Pgel). The modulus of hydrogels was estimated between 68.1 and 74.63 kPa that was similar to the normal cardiac modulus. Moreover, the elastic region increased by adding biomaterials to Pgel. The results of RT-PCR and ICC demonstrated that the most expression of early genes (GATA4, NKX2.5) was related to Pgel/AV/SF group. In contrast, the highest expression of other genes (GJA1, TNNI3, MYH6) was observed in Pgel/HA/SF. The presence of biomaterials in the structure of hydrogel can play a key role in cell fate and the induction of cell differentiation as a factor influencing mechanotransduction. These hydrogels hold an excellent promise to deliver hUSSCs into damaged tissue for cardiac regeneration.