The increased awareness of the ability of cells in detecting mechanical cues from the external environment [1] led to consider the possibility of triggering a cellular response by applying external mechanical forces [2]. In order to drive the commitment of differentiated cells and obtain in vitro engineered implants as replacement for bone fracture sites, a scaffold closely mimicking the 3D distribution of forces acting on bone cells in vivo is required and is still ongoing research. On this purpose, a composite scaffold embedded with collagen (cPCL) is proposed in this study as structure to transmit externally applied mechanical forces to embryonic human mesenchymal stem cells (hES-MPs) through a gelatinous matrix of collagen. A collagen concentration of 2 mg/ml and plasma treatment of scaffolds were selected as optimal conditions for survival and uniform seeding distribution of cells. Then, the second part of the study allowed to fully characterize, by mechanical testing and x-ray imaging, a novel hybrid scaffold able to provide an optimal environment for controlledbone progenitor cells growth. The objective of the last part of the study focused on the evaluation of how short bursts of compressive strain, applied as series of cycles at early stages (L1) and late stages (L2) of culture, affects cellular proliferation, bone tissue formation and the osteogenic response of hES-MPs. Short bursts of compression were found to strongly affect hES-MPs proliferation, suggesting cyclic compressive loading to delay the proliferation of samples compressed once. On the other side, L2 prevented proliferation to occur over 28 days, although greatly enhancing the production of mineral which, instead, was null for samples undergoing L1. This study underlined the existence of a strong link between proliferation and mineralization potential of cells and confirms the possibility to vary their response by short bursts of compression applied on hES-MPs seeded in 3D hybrid scaffolds.