*6.4. Zirconia (ZrO2)*

Zirconia is a structural ceramic that has been used for biomedical applications due to its biocompatibility, osseointegration potential, radiopacity, favorable mechanical properties, and in particular, its toughness [134–136]. When a crack occurs in zirconia, an internal tension is generated due to its propagation, transforming some grains from tetragonal to monoclinic (t→m), which increases the volume by about 5% [137]. As a result, compressive stress is generated, acting on the crack tip and hindering its propagation [137,138]. This phenomenon of "containment" of the crack is known as "transformation toughening", and since the discovery by Garvie et al. [139], it has been the focus of research for the biomedical application of zirconia.

Due to this favorable behavior, zirconia can supply the mechanical needs of a scaffold, so that it does not deform when submitted to loading and can be used to increase atrophic alveolar ridges or to replace the bone loss in the maxillofacial area [62]. Additionally, zirconia scaffolds can be manufactured by various techniques, resulting in different degrees of porosity, control of the geometric structure, and micro-roughness, which allows a good interconnection structure between the pores to support the growth of osteoblasts, vessels, and new bone [63,140].

However, despite offering superior properties, such as corrosion resistance, low friction coefficient, great wear resistance, hardness, and resistance to fracture propagation, zirconia scaffolds do not have the same efficiency in integration with bone tissue as phosphate-based ceramics [141]. Thus, nanocrystalline calcium phosphate powders, tricalcium phosphates, and/or bioactive glass have been associated with zirconia scaffolds, in the form of coatings or infiltrations, to increase biological activity, healing capacity, and osteogenesis within the adjacent tissue [138,140,142–144]. The current trend of using hybrid scaffolds, through the association of different materials, has been the path that tissue bone engineering has been seeking to obtain artificial structures more similar to bone biology.

#### **7. Techniques for Manufacturing Scaffolds**

Due to the several biomedical areas that benefit from tissue bone engineering, the rapid advance in the manufacture of 3D structures has been accompanied by the development and improvement of methods that aim to achieve the desired criteria for a scaffold. Scaffolds can be manufactured by conventional or additive manufacturing techniques and more recently, by 3D and 4D printing techniques [145,146]. Conventional techniques include methods such as solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, powder-forming, polymeric sponge replica method, and electrospinning [145,147–150], while among additive manufacturing techniques stereolithography, fused-deposition modeling, selective stand out laser sintering and electron beam melting stand out [145,151].

#### *7.1. Conventional Techniques*

Conventional techniques for manufacturing scaffolds use subtraction methods, in which part of the materials is removed so that the desired properties are achieved [152]. Generally, these techniques are easy to made and present low cost; however, these techniques may have limitations, such as the difficulty of obtaining structures with complex geometries [73]. The chemicals in the solvents used may not be completely removed from the scaffolding, being toxic to the newly formed tissue and the surrounding tissue of the host [153]. Table 2 describes the most commonly used conventional techniques and the scaffolds that can be obtained from them.


**Table 2.** Conventional manufacturing techniques: description and typical scaffold materials.
