**5. Specific bone scaffolds requirements**

The scaffold is one of the key elements of tissue engineering that provide mechanical support for cell adhesion and growth [115]. To design an ideal scaffold material selection, scaffold architecture, and scaffold fabrication techniques create important roles [116]. Bone scaffolds should provide a high porosity for cell adhesion, proliferation, and growth; meanwhile providing adequate mechanical properties during bone regeneration [117, 118]. It was suggested 75–95 vol% porosity is proper for bone scaffolds [119]. The osteoblast cells are in the range of 10–50 μm and prefer the larger pore size (100–200 μm) for growth and mineralization that could allow the penetration of macrophages, cell migration, and vascularization. Whereas lower pore size of this range leads to the creation of fibrous tissue and inhibits bone tissue regeneration [120].

The other important parameter for designing scaffolds is the swelling ratio. There are various properties affecting the swelling ratio such as hydrophilicity, cross-link density, porosity, pH, and the environmental characteristics [121–124]. A high swelling ratio facilitates fluid penetration and as a result enhances nutrition, oxygen, and waste material transportation, while the structures with an excess swelling ratio usually do not show adequate mechanical properties for bone healing [125]. The range of mechanical properties depends on the bone type, however, in general for elastic modulus range is reported 18.6 ± 28.8 GPa and 10–157 MPa for cortical and cancellous bone, respectively [126]. Therefore, it is expected the designed scaffold could provide sufficient mechanical properties for bone tissue during the regeneration procedure. Furthermore, the biodegradation ratio of the construct scaffolds should match the tissue growth rate [127]. Each bone requires a specific degradation ratio for example in spinal fusion regeneration it needs 9 months while it is suggested 3–6 months for craniomaxillofacial healing [119].
