BACKGROUND: Tissue engineering is an interdisciplinary field that integrates therapeutic agents, cells, biomaterials, and methodologies to regenerate damaged tissues. In bone tissue engineering, selecting and modifying materials to enhance mechanical strength, porosity, and pore size is critical for developing scaffolds that effectively support tissue regeneration. METHODS: A systematic review was conducted using Scopus, employing keywords such as "biomaterials for scaffold," "polymer for scaffold," and "freeze-drying synthesis method." After a rigorous screening and review process, 26 studies published between 2014 and 2024 were included in the analysis. RESULTS: The analysis revealed that lower freeze-drying temperatures lead to denser and more compact scaffold structures due to slower ice crystal formation. These scaffolds exhibit interconnected porous architectures critical for nutrient diffusion and cell infiltration. Key improvements in compressive strength and porosity were observed, making these scaffolds suitable for bone tissue engineering applications. CONCLUSIONS: Freeze-drying is a sustainable and effective method for scaffold fabrication, enabling the use of eco-friendly biomaterials. The resulting scaffolds demonstrate superior compressive strength and high porosity, facilitating effective cell attachment and proliferation. This study underscores the potential of freeze-drying methodologies in advancing scaffold design for bone tissue regeneration.