**3. Strengths of titanium dioxide in bone tissue engineering**

Titanium oxide has been extensively investigated as a biomaterial due to its excellent biocompatibility and superior corrosion/erosion resistance, as well as high stability [40]. The addition of titania particulates to HA has attracted considerable attention based on the assumption that titania is capable of enhancing osteoblast adhesion and inducing cell growth [41].

Titanium oxides (anatase and rutile) are light and high-resistance bioactive materials widely employed in dental and bone application due to their capacity of forming strong bonds with bone tissue via the formation of a tightly bound apatite layer on their surface [33, 42–44].

In particular, rutile is a very interesting biomaterial for developing bioactive ceramic composites with improved mechanical performances [45].

In this respect, in spite of the numerous studies and applications of HA/TiO2 composites as bioactive coatings for load-bearing titanium prostheses [46–49], only a few studies were reported so far about the development of bulk TiO2 -containing composites addressed to the development of bone scaffolds [50, 51].

The use of spark plasma sintering and hot pressing to obtain TCP/TiO2 composites from hydroxyapatite and titania nanopowders has been previously reported [51, 52], whereas Nath et al. used metallic titanium by traditional sintering at different maximum temperatures [50]. In these works, an accurate physicochemical description of the phenomena occurring after thermal treatment of HA/TiO2 mixtures pointed out the capability of TiO2 to favor the decomposition of HA, with subsequent formation of β-TCP and CaTiO<sup>3</sup> , according to the following reaction:

$$\text{Ca}\_{10}\text{(PO}\_4\text{)}\_{6}\text{(OH)}\_2 + \text{TiO}\_2 \rightarrow 3\text{Ca}\_3\text{(PO}\_4\text{)}\_2 + \text{CaTiO}\_3 + \text{H}\_2\text{O}\uparrow\tag{1}$$

In particular, good cell adhesion and proliferation in contact with bulk TCP/TiO2 composites were reported [50]. This finding was also confirmed by Hu et al. [47] and Sato et al. [48], which reported good cell behavior in contact with coatings of similar compositions.

### **4. A focus on calcium phosphate/titania bulk composite materials**

when Hench and coworkers invented Bioglass®, a silico-phosphate-based glass with composition close to that of bone mineral [20]. However, due to their nature, bioactive glasses were not indicated for scaffold reinforcement; however, the presence of silicon in bone scaffolds has always been addressed as promoter of new bone formation in vivo, due to its ability to be a center for nucleation of apatite phase in physiological environment [33]. On this basis, calcium silicate phases such as dicalcium and tricalcium silicate, as well as wollastonite or

particular, the development of composites made of HA reinforced with dicalcium silicate was investigated [36], on the basis of its high flexure strength (≈200 MPa) and reduced elastic modulus (≈40 GPa) [37], compared with HA, thus resulting as promising compositions for bone scaffolding. As a main drawback, calcium silicates exist in a variety of polymorphs stable in different conditions of temperature [38], thus making difficult to obtain pure phases

A different system that recently attracted the interest of scientists is given by titanium (Ti) and

sively used as implantation materials due to their favorable properties such as lower modulus, good tensile strength, excellent biocompatibility, and enhanced corrosion resistance [39].

Titanium oxide has been extensively investigated as a biomaterial due to its excellent biocompatibility and superior corrosion/erosion resistance, as well as high stability [40]. The addition of titania particulates to HA has attracted considerable attention based on the assumption that

Titanium oxides (anatase and rutile) are light and high-resistance bioactive materials widely employed in dental and bone application due to their capacity of forming strong bonds with bone tissue via the formation of a tightly bound apatite layer on their surface [33, 42–44].

In particular, rutile is a very interesting biomaterial for developing bioactive ceramic compos-

as bioactive coatings for load-bearing titanium prostheses [46–49], only a few studies were

hydroxyapatite and titania nanopowders has been previously reported [51, 52], whereas Nath et al. used metallic titanium by traditional sintering at different maximum temperatures [50]. In these works, an accurate physicochemical description of the phenomena occurring after

mixtures pointed out the capability of TiO2

and avoid decomposition detrimental for the mechanical properties.

**3. Strengths of titanium dioxide in bone tissue engineering**

titania is capable of enhancing osteoblast adhesion and inducing cell growth [41].

In this respect, in spite of the numerous studies and applications of HA/TiO2

The use of spark plasma sintering and hot pressing to obtain TCP/TiO2

position of HA, with subsequent formation of β-TCP and CaTiO<sup>3</sup>

), were widely investigated as scaffolds or cements [34, 35]. In

), which have been already validated and exten-

composites

composites from

to favor the decom-

, according to the following


pseudo-wollastonite (CaSiO3

48 Application of Titanium Dioxide

its alloys, particularly titanium dioxide (TiO2

ites with improved mechanical performances [45].

reported so far about the development of bulk TiO2

development of bone scaffolds [50, 51].

thermal treatment of HA/TiO2

reaction:

Most studies have been devoted so far to the investigation of calcium phosphate sintering and the mechanical properties of pure TCP or the pure TiO2 . However, a little work has been reported on the performances of TCP-TiO2 composites [28, 52, 53]. These papers focused on the synthesis of TCP-TiO2 composites where titania nanoparticles could enhance the mechanical properties of calcium phosphate matrices, without penalizing biocompatibility.

In particular, Sprio et al. proposed a pressureless air sintering of mixed hydroxyapatite and titania (TiO2 ) powders [28]; the sintering process was optimized to achieve dense ceramic bodies consisting in a bioactive/bioresorbable β-TCP matrix reinforced with defined amounts of submicron-sized titania particles.

A crucial step in the development of ceramic composites is the control of particle size and the driving energy for thermal consolidation processes [54]. Indeed, homogeneous ceramic composites come from adequately prepared powder mixtures, possibly preventing particle agglomeration. In this respect, HA powder was calcined at 900°C to increase the particle size whereas reducing surface activity possibly promoting the formation of particle clusters and to promote the achievement of composites with homogeneous microstructure [55]. On the other hand, an excessive increase of the HA particle size can reduce the driving energy for further HA grain growth during sintering, thus resulting in limited consolidation [54]. This comes very relevant when designing materials for load-bearing applications which need improved mechanical properties.

Therefore, a detailed study of the phase composition of HA/TiO2 mixtures with temperature was mandatory; several mixtures were prepared (HA/TiO2 = 90:10, 80:20, 70:30 vol%) and treated at different temperatures. As a general rule, the starting phase composition remained unchanged upon firing at temperatures up to 700°C, where the transformation of anatase into rutile started to take place; at higher temperatures, anatase underwent progressively increasing transformation in rutile and completely disappeared at 850°C. Therefore, even though titanium dioxide is present in different polymorphs, this does not result as a drawback, as above certain temperatures, of interest for ceramic sintering; the thermodynamically stable phase is always rutile.

As induced by the presence of rutile, the decomposition of HA phase into β-TCP occurred at relatively low temperatures (950°C); in the same temperature range, the formation of perovskite (CaTiO3 ) was also detected. At higher temperatures, the phase composition of the mixture resulted unchanged up to 1250°C, when part of β-TCP was converted into the high-temperature polymorph α-TCP [56]; the raising of the firing temperature up to 1300°C promoted a further increase of the α-TCP content. Therefore, despite the highest volume shrinkage was detected at 1300°C by dilatometric analysis, the final sintering temperature was limited to 1250°C. Indeed, as α-TCP is characterized by very high solubility in physiological environment [56], its presence may result in excessively fast resorption in vivo, hindering an adequate bone regeneration process. Moreover, the transformation of β-TCP in α-TCP is associated with an average 10% volume increase, which potentially penalizes the mechanical performances by micro-damages. A full consolidation of the composites was obtained by applying a dwell time of 1 h.

On this basis, the reinforcing mechanisms of titania particles embedded in the sintered composites were investigated by scanning electron microscopy, thus revealing that the presence of different amounts of titania does not strongly influence grain growth. Moreover, the spatial distribution of the submicron grains of titania (the brighter areas) could be still recognized also showing that, in high concentrations, they tended to coalesce in an interconnected framework (**Figure 3**).

The increase of mechanical properties was shown to depend strongly on the amount of titania particles introduced in the calcium phosphate matrix (**Figure 4**) [28].

Due to the different mechanical and thermal properties of the constituent phases, possible toughening mechanisms operating in these composites are crack deflection [57], crack bowing [58], residual stress [59], and microcracking toughening [60].

The Knoop hardness increased almost linearly with the content of TiO2 , as this phase is much harder than β-TCP. In literature, hardness is reported to be 10 GPa for TiO<sup>2</sup> [61] and 3.43 GPa for β-TCP [62].

**Figure 3.** Schematic representation of the TCP/TiO2 composite microstructure, evidencing the interconnection of TiO2 grains.

Composite Calcium Phosphate/Titania Scaffolds in Bone Tissue Engineering http://dx.doi.org/10.5772/intechopen.68867 51

**Figure 4.** Plot of the flexural strength and Knoop hardness as a function of initial TiO<sup>2</sup> content.

as α-TCP is characterized by very high solubility in physiological environment [56], its presence may result in excessively fast resorption in vivo, hindering an adequate bone regeneration process. Moreover, the transformation of β-TCP in α-TCP is associated with an average 10% volume increase, which potentially penalizes the mechanical performances by micro-damages.

On this basis, the reinforcing mechanisms of titania particles embedded in the sintered composites were investigated by scanning electron microscopy, thus revealing that the presence of different amounts of titania does not strongly influence grain growth. Moreover, the spatial distribution of the submicron grains of titania (the brighter areas) could be still recognized also showing that, in high concentrations, they tended to coalesce in an interconnected frame-

The increase of mechanical properties was shown to depend strongly on the amount of titania

Due to the different mechanical and thermal properties of the constituent phases, possible toughening mechanisms operating in these composites are crack deflection [57], crack bowing

, as this phase is much

composite microstructure, evidencing the interconnection of TiO2

[61] and 3.43 GPa for

A full consolidation of the composites was obtained by applying a dwell time of 1 h.

particles introduced in the calcium phosphate matrix (**Figure 4**) [28].

The Knoop hardness increased almost linearly with the content of TiO2

harder than β-TCP. In literature, hardness is reported to be 10 GPa for TiO<sup>2</sup>

[58], residual stress [59], and microcracking toughening [60].

**Figure 3.** Schematic representation of the TCP/TiO2

work (**Figure 3**).

50 Application of Titanium Dioxide

β-TCP [62].

grains.

TiO2 -based composites exhibited mechanical properties compliant with those of human cortical bone [33]. In this respect, the sample containing about 20 vol% of TiO2 was of particular interest, as it represented the maximum level for successful strengthening of the final composite, at least in the range 0–30 vol% (**Figure 4**). This was attributed to a reduced number of microstructural defects, unavoidably generated by adding excessive amounts of titania. With the aim to develop porous bioactive scaffolds, the achievement of good mechanical properties by introducing limited amounts of bioactive, but nonresorbable, reinforcing components is a relevant point that place TCP/TiO2 composites as very promising materials for the regeneration of load-bearing bone segments.
