Some basic requirements of bone tissue engineering include cells derived from bone tissues, three-dimensional (3D) scaffold materials, and osteogenic factors. In this framework, the critical architecture of the scaffolds plays a crucial role to support and assist the adhesion of the cells, and the subsequent tissue repairs. However, numerous traditional methods suffer from certain drawbacks, such as multi-step preparation, poor reproducibility, high complexity, difficulty in controlling the porous architectures, the shape of the scaffolds, and the existence of solvent residue, which limits their applicability. In this work, we fabricated innovative poly(lactic-co-glycolic acid) (PLGA) porous scaffolds, using 3D-printing technology, to overcome the shortcomings of traditional approaches. In addition, the printing parameters were critically optimized for obtaining scaffolds with normal morphology, appropriate porous architectures, and sufficient mechanical properties, for the accommodation of the bone cells. Various evaluation studies, including the exploration of mechanical properties (compressive strength and yield stress) for different thicknesses, and change of structure (printing angle) and porosity, were performed. Particularly, the degradation rate of the 3D scaffolds, printed in the optimized conditions, in the presence of hydrolytic, as well as enzymatic conditions were investigated. Their assessments were evaluated using the thermal gravimetric analyzer (TGA), differential scanning calorimetry (DSC), and gel permeation chromatography (GPC). These porous scaffolds, with their biocompatibility, biodegradation ability, and mechanical properties, have enabled the embryonic osteoblast precursor cells (MC3T3-E1), to adhere and proliferate in the porous architectures, with increasing time. The generation of highly porous 3D scaffolds, based on 3D printing technology, and their critical evaluation, through various investigations, may undoubtedly provide a reference for further investigations and guide critical optimization of scaffold fabrication, for tissue regeneration.