**10.9.1. Biological apatite in bone tissue engineering**

Tissue engineering (TE) techniques were developed to recover or enhance lost tissue func‐ tion and structure. In biological hard tissues, for example, lost portions can be effectively reconstructed by the control of environmentalfactors, physical stimulation, addition of growth factors and by the use of degradable materials. These factors strongly facilitate the regenera‐ tion of macroscopic shape of defected hard tissues. Nevertheless, the differences in micro‐ structure, and also in mechanical and physical properties, between regenerated and original hard tissues must be examined prior to clinical application [112],[113],[114].

For in vitro engineering of living tissues, cultured cells are grown on bioactive degradable substrates (scaffolds8 ) that provide the physical and chemical cues to guide their differentia‐ tion and assembly into three-dimensional structures. One of the most critical issues in TE is the realization of scaffolds with specific physical, mechanical and biological properties. Scaffolds act as substrate for cellular growth, proliferation and the support for new tissue

<sup>8</sup> Scaffolds might be defined as artificial structure capable of supporting the three-dimensional tissue formation, which allows the cell attachment and migration, the delivery and retaining of cells and biochemical factors and enables the diffusion of vital cell nutrients and expressed products. In the case of bone, scaffolds should replicate its architecture and three-dimensional structure with predetermined density, hierarchical pore distribution and interconnected pathways [109],[115].

formation. Biomaterials and fabrication technologies play a key role in tissue engineering. Materials used for tissue engineering applications must be designed to stimulate specific cell response on the molecular level. They should elicit specific interactions with the cell and thereby direct cell attachment, proliferation, differentiation and extracellular matrix produc‐ tion and organization [109],[115]:


Inorganic-organic composites aiming at mimicking the composite nature ofreal bone combine the toughness of the polymer phase with the compressive strength of an inorganic one to generate bioactive materials with improved mechanical properties and degradation profiles. Hydroxylapatite (HAP) is widely used as a biocompatible ceramic material in many areas of medicine, but mainly for the contact with bone tissue, due to its resemblance to mineral bone [115].

Under normal conditions, human body fluid is supersaturated with respect to apatite, so that, when apatite nuclei form, crystals can grow spontaneously. Chemical species that are capable of supporting the nucleation of apatite are calcium and silicate ions, while, in contrast, phosphate ion does not affect this process. Hence, ceramics that release the former men‐ tioned ions are capable of developing the surface apatite layer when exposed to human body fluids. This explains why glasses that do not contain P2O5 are able to develop this surface layer and show greater bioactivity than glasses containing P2O5, even if the latter compositions approximate to that of hydroxyapatite [116].
