Critical-sized bone defect repair remains a substantial challenge in clinical settings and requires bone grafts or bone substitute materials. However, existing biomaterials often do not meet the clinical requirements of structural support, osteoinductive property, and controllable biodegradability. To treat large-scale bone defects, the development of three-dimensional (3D) porous scaffolds has received considerable focus within bone engineering. A variety of biomaterials and manufacturing methods, including 3D printing, have emerged to fabricate patient-specific bioactive scaffolds that possess controlled micro-architectures for bridging bone defects in complex configurations. During the last decade, with the development of the 3D printing industry, a large number of tissue-engineered scaffolds have been created for preclinical and clinical applications using novel materials and innovative technologies. Thus, this review provides a brief overview of current progress in existing biomaterials and tissue engineering scaffolds prepared by 3D printing technologies, with an emphasis on the material selection, scaffold design optimization, and their preclinical and clinical applications in the repair of critical-sized bone defects. Furthermore, it will elaborate on the current limitations and potential future prospects of 3D printing technology. STATEMENT OF SIGNIFICANCE: 3D printing has emerged as a critical fabrication process for bone engineering due to its ability to control bulk geometry and internal structure of tissue scaffolds. The advancement of bioprinting methods and compatible ink materials for bone engineering have been a major focus to develop optimal 3D scaffolds for bone defect repair. Achieving a successful balance of cellular function, cellular viability, and mechanical integrity under load-bearing conditions is critical. Hybridization of natural and synthetic polymer-based materials is a promising approach to create novel tissue engineered scaffolds that combines the advantages of both materials and meets various requirements, including biological activity, mechanical strength, easy fabrication and controllable degradation. 3D printing is linked to the future of bone grafts to create on-demand patient-specific scaffolds.