Abstract A suitable scaffold architecture is always desirable to get a favorable tissue response for bone tissue engineering. In this regard, a fluid-structure interaction analysis was carried out on different porous scaffolds to observe the in vitro mechanical responses due to fluid flow, followed by a submodeling method to obtain the cellular deformation and strain. Different types of scaffolds were designed based on different porosity and architecture. The cell was modelled with cytoplasm, nucleus, cell membrane, and cytoskeletons. The main objective of the study is to examine the variation of cellular responses due to different porosity and architecture of the scaffold. The results of this study highlight that permeability is higher in the case of gyroid structure and wall shear stress (WSS) is higher in the case of diamond structure. The permeability of all scaffolds increases with the increase of porosity. The opposite trend is shown in the case of WSS within scaffolds. The cell is showing higher deformation when it is placed on the front position of the scaffold towards the direction of fluid flow. This study will guide us in predicting an ideal scaffold for better cell growth.