Design and fabrication of optimal scaffolds for bone tissue repair is a multi-physics problem targeting osteoconductive, biodegradable material designs with loading of necessary growth factors. Therefore optimal tissue regeneration based on accurate analysis models including the degradation behavior of biomaterials is a critical design requirement (Byrne et al., 2007). In order to explore bone regeneration, cell response to growth factors and existing intracellular signaling pathways driving bone regeneration through transcription factors should be taken into consideration considering degradation of the scaffold (Sun et al., 2013). In this work, this problem is addressed by solving time dependent hydrolysis reaction equations coupled to a reaction-diffusion equation and a set of ordinary differential equations representing release of growth factors and intracellular signaling pathway, respectively. The evolution of bone scaffold degradation, growth factor release and intracellular signaling pathway are conducted as a parametric study based on the effect of pore size of the scaffold within a FEM based modeling environment. Parameters such as degradation rate constant, diffusivity of water through scaffold are tuned based on existing computational models and experimental data in literature. In addition to providing an efficient tuning ability for design parameters, computational models offer significant advantages such as time and cost savings of experimental design and validation processes (Wang et al., 2020). Therefore, the aim of this study is to analyze the effect of porosity on the scaffold degradation, growth factor release and cell response during the bone healing process for a regular structured 3D cubic scaffold with aligned pores based on coupled reaction-diffusion PDE equations. COMSOL Multiphysics® was used to create a unified modeling framework that should allow for additional multi-physical effects such as mechano-biology based regeneration, diffusion of MSCs and angiogenesis to be considered within future design studies. Degradation profiles for scaffolds with different pore sizes and porosities were analyzed and the effect of degradation on growth factor release profiles and cellular response were observed. It has been shown that the pore size and porosity of a bone scaffold affects the bone regeneration process through dynamic interaction between growth factor release profiles and their regulatory mechanism on transcription factors with scaffold degradation.