Extensive bone loss is often experienced in the treatment of trauma, tumors, infections, congenital diseases, and disuse. Autologous bone grafting is considered the gold standard for solving these demands due to its osteogenic, osteoinductive, and osteoconductive characteristics. Thus, the need more surgical sites, volumetric limitations, risk of infections, and in some situations, the cost of hospitalization should be considered. 3D printing biomanufatured calcium phosphate-based scaffolds raises as osteoconductive materials for bone reconstructions. Volumetric disposability, biocompatible performance and easy handling are some benefits of these new options. Advances in biology and tissue engineering technologies are making it possible to use materials and techniques together to achieve better results. Osteogenic properties of ozone are being mapped which make this material a possible biofunctionalizer 3D scaffolds and other materials for tissue engineering. Thus, deficiencies such as the osteogenic potential and remodeling ability of the scaffolds still remains as limitations. Ozone therapy has been used as adjuvant in regeneration and repair processes by releasing free oxygen and increasing the responsiveness of cellular metabolism and generation of vital energy. Therefore, the release responses of inflammatory mediators, growth factors, and cytokines become more effective, especially in situations in which they are deficient, such as at advanced ages. The objective of this literature review is to evaluate the role of ozone therapy to optimize cellular response for the local response of bone formation at critical size defect sites reconstructed with 3D biomanufacturing
scaffolds.