Stem cells appear to be one of the most promising cell types to be used in scaffolds for tissue engineering purposes. It’s necessary to know how to force the cells to differentiate into the desired lineage.The intrinsic properties of the substrate (such as elasticity and micromechanical characteristics) are attributed by the cells behavior after attaching to the structure of a synthesized scaffold. Thermoplastic elastomers based on polypropylene (PP) and ethylene diene rubber (EPDM) are expected to be good candidate for these purposes, as their micromorphology, mechanical behavior, and surface stiffness can be engineered for desired bioactivities. In the present study, attempts have been made to evaluate the influence of micromechanical properties, elasticity and viscoelastic characteristics of PP/EPDM thermoplastic vulcanizates (TPVs) upon mesenchymal stem cells attachment, proliferation and differentiation. For these purposes, two different dynamically vulcanized PP/EPDM with different morphology and stiffness have been employed. Nano hydroxyapatite (HA) has been incorporated as bioagent in the presence of maleated PP as interfacial compatibilizer. Solid viscoelastic behavior, surface roughness and surface morphology of the samples were evaluated by dynamically mechanical thermal analysis (DMTA), atomic force microscopy (AFM) and scanning electron microscope (SEM) respectively. Bone marrow-derived stem cells were isolated from a rabbit and cultured on the surface of samples showed excellent attachment and proliferation. However, degree of cell proliferation was found to be much better for the samples generated by nano hydroxyapatite and PP-g-MAH. Extent of cells differentiation showed to be affected by the TPVs surface hardness and micromorphology. Real time PCR was performed on various nanocomposite TPV samples with different mechanical behavior to evaluate gene expression and differentiation to bone tissue. The extent of cell differentiation was found to be governed by the viscose or damping behavior of the TPV matrix. In another word, the higher mechanical time dependency of the substrate, the more retarded cells differentiation.