With a global prevalence of more than 2 million graft procedures per year, bone grafts are one of the most common transplants. [1][2][3][4][5] Small bone defects can be restored naturally, while large defects created by severe trauma, accidents, or tissue resection are unable to heal on their own. [6] As a rigid organ in humans and live animals, bone supports and protects different organs, tissues, and facilitates the mobility of the body. [7,8] These unique applications of bone are mainly attributed to the hierarchical architecture of bone, which mainly consists of the soft collagen protein and stiffer apatite mineral. [9] The overall stiffness of bone is primarily controlled by the natural mineral content as well as collagen to mineral ratio. [7,10] The mechanism of bone regeneration can be categorized as direct or indirect healing. [11] The size of fracture is one of the important factors that affects the bone healing mechanism. Direct bone healing mainly starts when a small and narrow (≤0.1 mm) fracture occurs, and the site of a fracture is rigidly stabilized. During direct bone healing, the small gap is covered directly by continuous ossification, following Haversian remodeling in a serial order. [12] Larger defects mostly heal by the indirect bone healing via various parallel events, such as blood clotting, inflammatory response, fibrocartilage callus formation, intramembranous and endochondral ossification, and results in bone remodeling. [11,12] A critical size defect is defined as the minimum defect dimension which is incapable of repairing without intervention. Per Food and Drug Administration (FDA) recognized standard ASTM F2721, in a critical size defect, the length of defect is at least 1.5-2 times the diameter of the selected bone. Critically sized defects can overwhelm the tissue regeneration capacity and lead to permanent disabilities. [13,14] Thus, surgical interventions are needed for the treatment of critically sized defects (Figure 1).Bone mimetic grafts, with hierarchical structure, and effective functionality could be engineered by merging suitable biomaterials, [7] cells, [15] and bioactive agents. [16] To design biomimetic bone scaffolds, a combination of nano-/microtechnologies with macrotechnologies is required. [17] Although many technologies have been developed for bone tissue engineering incorporating