*6.1. Hydroxyapatite (HAp)*

Hydroxyapatite, a hydrated calcium phosphate (Ca10(PO4)6(OH)2), is a mineral present in vertebrates (about 55% of the bone composition, 96% of dental enamel composition, and 70% of dentin), which acts as a reserve of calcium and phosphorus [58,110]. For use as a graft material, it can be obtained by deproteinizing bone tissue (natural HAp, usually from bovine tissue) or by precipitating aqueous solutions from phosphates (synthetic HAp) [114]. Natural and synthetic HAp are thermodynamically stable at physiological pH and actively participate in bone bonds, forming a strong chemical bond with bone tissue [58]. The HAp surface allows the interaction of dipole-type bonds, causing water molecules and also proteins and collagen to be adsorbed on the surface, thus inducing tissue regeneration [59].

Synthetic HAp has been the most widely used clinically, characterized by being a biocompatible and osteoconductive material that presents high stability in aqueous media [115]. It is commercialized in the form of dense or porous ceramics, in blocks, granules, or coatings, being used in the repair of bone defects, an increase of alveolar ridge, guided regeneration of bone tissues, and buccomaxillofacial reconstructions [116,117]. Compared with natural HAp, synthetic HAp has a higher crystallinity, which results in slower degradation that can last 4 to 5 years [116]. Therefore, scaffolds manufactured in HAp maintain their geometric shape for a longer time during the regeneration of bone tissue [117].

However, in some clinical situations, the rate of HAp degradation may be out of step with bone formation [118]. When compared to other calcium phosphates (amorphous tricalcium phosphate: 25.7 to 32.7 g/L; calcium monophosphate monohydrate: about 18 g/L; anhydrous calcium monophosphate: about 17 g/L), the rate of HAp reabsorption is considered to be quite low (about 0.0094 g/L) [119,120]. Thus, studies have suggested replacing phosphate groups (PO4 <sup>3</sup>−) with carbonate groups (CO3 <sup>2</sup>−) (carbonated or carboapatite HAp), which modifies the crystalline structure of HAp, increasing its solubility and, consequently, its clinical application [116,120].
