One of the issues in bone tissue engineering is the need of having a tridimensional support for cell growth with good structural integrity as well as good transport properties. In addition, these requirements change with the patient’s needs and the bone site where the graft is applied. To address this challenge, several strategies have been developed in the last decades to obtain the optimal configuration of a scaffold for bone tissue engineering. In our research group, two approaches have been studied. Topology optimization of structures was used to define the pore configuration of a periodic scaffold with optimized stiffness and permeability and lately using fixed topology structures based on Triply periodic minimal surfaces (TPMS) that should be carefully selected to respond to the application requisites. The complex structures obtained in both cases are suitable to be produced by additive manufacturing which has been a very fast evolution with some techniques able to use biocompatible materials and to build parts with a high resolution necessary to a feasible reproduction of the scaffold design. This talk aims to show how these two approaches can provide insights for the development of bone substitutes toward clinical translation. Recent experimental and computational results will be presented to investigate how TPMS with different configurations, together with different geometries and porosity levels, affects the biomechanical performance of TPMS-based scaffolds. Finally graded TPMS structures are explored to build substitutes to repair large bone defects.