**1. Introduction**

Calcium phosphates (CaP) have been sought as biomaterials for reconstruction of bone defect in maxillofacial, dental and orthopaedic applications [1-31]. Calcium phosphates have been used clinically to repair bone defects for many years. Calcium phosphates such as hydroxyapatite (Ca10(PO4)6(OH)2, HAp), fluorapatite (Ca10(PO4)6F2, FAp), tricalci‐ um phosphate (Ca3(PO4)2, TCP), TCP-HAp composites and TCP-FAp composites are used for medical and dental applications [3, 10-29]. In general, this concept is determined by advantageous balances of more stable (frequent by hydroxyapatite or fluorapatite) and more resorbable (typically tricalcium phosphate) phases of calcium phosphates, while the optimum ratios depend on the particular applications. The complete list of known calci‐ um phosphates, including their major properties (such, the chemical formula, solubility data) is given in Table 1. The detailed information about calcium phosphates, their syn‐ thesis, structure, chemistry, other properties and biomedical applications have been com‐ prehensively reviewed recently in reference [24].

Calcium phosphate-based biomaterials and bioceramics are now used in a number of differ‐ ent applications throughout the body, covering all areas of the skeleton. Applications in‐ clude dental implants, percutaneous devices and use in periodontal treatment, treatment of bone defects, fracture treatment, total joint replacement (bone augmentation), orthopedics, cranio-maxillofacial reconstruction, otolaryngology and spinal surgery [32-35]. Depending upon whether a bioresorbable or a bioactive material is desired, different calcium ortho‐ phosphates might be used.

© 2013 Sakka et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In the past, many implantations failed because of infection or a lack of knowledge about the toxicity of the selected materials. In this frame, the use of calcium phosphates is logical due to their similarity to the mineral phase of bone and teeth [36-40]. However, according to available literature, the first attempt to use calcium phosphates as an artificial material to re‐ pair surgically-created defects in rabbits was performed in 1920 [41]. More than fifty years later, the first dental application of a calcium phosphate (erroneously described as TCP) in surgically-created periodontal defects [42] and the use of dense HAp cylinders for immedi‐ ate tooth root replacement were reported [43]. Since Levitt et al. described a method of pre‐ paring an apatite bioceramics from FAp and suggested its possible use in medical applications in 1969[44]. According to the available databases, the first paper with the term ''bioceramics'' in the abstract was published in 1971 [45], while those with that term in the title were published in 1972 [46-47]. However, application of ceramic materials as prostheses had been known before [48-49]. Further historical details might be found in literature [50]. Commercialization of the dental and surgical applications of Hap-based bioceramics occur‐ red in the 1980's, largely through the pioneering efforts by Jarcho [51], de Groot [52] and Ao‐ ki [53]. Due to that, HAp has become a bioceramic of reference in the field of calcium phosphates for biomedical applications. Preparation and biomedical applications of apatites derived from sea corals (coralline HAp) [54–56] and bovine bone were reported at the same time [57]. Since 1990, several other calcium phosphate cements have been developed [58-62], injectable cements have been formulated [63], and growth factors have been delivered via these cements [64]. The tetracalcium phosphate [TTCP: Ca4(PO4)2O] and dicalcium phos‐ phate anhydrous [DCPA: CaHPO4] system was approved in 1996 by the Food and Drug Ad‐ ministration (FDA) for repairing craniofacial defects in humans, thus becoming the first TTCP–DCPA system for clinical use [65]. However, due to its brittleness and weakness, the use of TTCP–DCPA system was limited to the reconstruction of non-stress-bearing bone [66-67]. To expand the use of TTCP–DCPA system to a wide range of load-bearing maxillo‐ facial and orthopedic repairs, recent studies have developed natural biopolymers that are elastomeric, biocompatible and resorbable [68]. Calcium phosphates in a number of forms and compositions are currently either in use or under consideration in many areas of den‐ tistry and orthopedics. For example, bulk materials, available in dense and porous forms, are used for alveolar ridge augmentation, immediate tooth replacement and maxillofacial re‐ construction [35, 69]. Other examples include orbital implants (Bio-Eye) [70-71], increment of the hearing ossicles, spine fusion and repair of bone defects [72-73]. In order to permit growth of new bone onto bone defects, a suitable bioresorbable material should fill the de‐ fects. Otherwise, in-growth of fibrous tissue might prevent bone formation within the de‐ fects [69-73]. Today, a large number of different calcium phosphate bioceramics for the treatment of various defects are available on the market.

The performance of living tissues is the result of millions of years of evolution, while the performance of acceptable artificial substitutions those man has designed to repair damaged hard tissues are only a few decades old. Archaeological findings exhibited in museums showed that materials used to replace missing human bones and teeth have included animal or human (from corpses) bones and teeth, shells, corals, ivory (elephant tusk), wood, as well as some metals (gold or silver). For instance, the Etruscans learned to substitute missing teeth with bridges made from artificial teeth carved from the bones of oxen, while in ancient Phoenicia loose teeth were bound together with gold wires for tying artificial ones to neigh‐ boring teeth.


(a): Solubility at 25°C (pKs = -logKs);

In the past, many implantations failed because of infection or a lack of knowledge about the toxicity of the selected materials. In this frame, the use of calcium phosphates is logical due to their similarity to the mineral phase of bone and teeth [36-40]. However, according to available literature, the first attempt to use calcium phosphates as an artificial material to re‐ pair surgically-created defects in rabbits was performed in 1920 [41]. More than fifty years later, the first dental application of a calcium phosphate (erroneously described as TCP) in surgically-created periodontal defects [42] and the use of dense HAp cylinders for immedi‐ ate tooth root replacement were reported [43]. Since Levitt et al. described a method of pre‐ paring an apatite bioceramics from FAp and suggested its possible use in medical applications in 1969[44]. According to the available databases, the first paper with the term ''bioceramics'' in the abstract was published in 1971 [45], while those with that term in the title were published in 1972 [46-47]. However, application of ceramic materials as prostheses had been known before [48-49]. Further historical details might be found in literature [50]. Commercialization of the dental and surgical applications of Hap-based bioceramics occur‐ red in the 1980's, largely through the pioneering efforts by Jarcho [51], de Groot [52] and Ao‐ ki [53]. Due to that, HAp has become a bioceramic of reference in the field of calcium phosphates for biomedical applications. Preparation and biomedical applications of apatites derived from sea corals (coralline HAp) [54–56] and bovine bone were reported at the same time [57]. Since 1990, several other calcium phosphate cements have been developed [58-62], injectable cements have been formulated [63], and growth factors have been delivered via these cements [64]. The tetracalcium phosphate [TTCP: Ca4(PO4)2O] and dicalcium phos‐ phate anhydrous [DCPA: CaHPO4] system was approved in 1996 by the Food and Drug Ad‐ ministration (FDA) for repairing craniofacial defects in humans, thus becoming the first TTCP–DCPA system for clinical use [65]. However, due to its brittleness and weakness, the use of TTCP–DCPA system was limited to the reconstruction of non-stress-bearing bone [66-67]. To expand the use of TTCP–DCPA system to a wide range of load-bearing maxillo‐ facial and orthopedic repairs, recent studies have developed natural biopolymers that are elastomeric, biocompatible and resorbable [68]. Calcium phosphates in a number of forms and compositions are currently either in use or under consideration in many areas of den‐ tistry and orthopedics. For example, bulk materials, available in dense and porous forms, are used for alveolar ridge augmentation, immediate tooth replacement and maxillofacial re‐ construction [35, 69]. Other examples include orbital implants (Bio-Eye) [70-71], increment of the hearing ossicles, spine fusion and repair of bone defects [72-73]. In order to permit growth of new bone onto bone defects, a suitable bioresorbable material should fill the de‐ fects. Otherwise, in-growth of fibrous tissue might prevent bone formation within the de‐ fects [69-73]. Today, a large number of different calcium phosphate bioceramics for the

24 Advances in Biomaterials Science and Biomedical Applications

treatment of various defects are available on the market.

The performance of living tissues is the result of millions of years of evolution, while the performance of acceptable artificial substitutions those man has designed to repair damaged hard tissues are only a few decades old. Archaeological findings exhibited in museums showed that materials used to replace missing human bones and teeth have included animal or human (from corpses) bones and teeth, shells, corals, ivory (elephant tusk), wood, as well as some metals (gold or silver). For instance, the Etruscans learned to substitute missing (b) : Cannot be measured precisely.

**Table 1.** Calcium phosphates and their major properties [3, 24]

Calcium phosphates are established materials for the augmentation of bone defects. They are available as allogenic, sintered materials. Unfortunately, these calcium phosphates ex‐ hibit relatively poor tensile and shear properties [74]. In practice, the strength of the calcium phosphate cements is lower than that of bone, teeth, or sintered calcium phosphate biocer‐ amics [75] and, together with their inherent brittleness, restricts their use to non-load bear‐ ing defects [76] or pure compression loading [74]. Typical applications are the treatment of maxillo-facial defects or deformities [77] and cranio facial repair [78] or augmentation of spine and tibial plateau [74]. A successful improvement of the mechanical properties would significantly extend the applicability of calcium phosphates [79] and can be achieved by forming composite materials [80]. Second phase additives to the calcium phosphate compo‐ sites have been either fibrous reinforcements or bioinert oxides that interpenetrate the po‐ rous matrix.

Hydroxyapatite and other calcium phosphates bioceramics are important for hard tissue re‐ pair because of their similarity to the minerals in natural bone, and their excellent biocom‐ patibility and bioactivity [81-86]. When implanted in an osseous site, bone bioactive materials such as HAp and other CaP implants and coatings provide an ideal environment for cellular reaction and colonization by osteoblasts. This leads to a tissue response termed osteoconduction in which bone grows on and bonds to the implant, promoting a functional interface [81, 84, 87]. Extensive efforts have significantly improved the properties and per‐ formance of HAp and other CaP based implants [88-92]. Calcium phosphate cements can be molded or injected to form a scaffold in situ, which can be resorbed and replaced by new bone [93, 65-67]. Chemically, the vast majority of calcium phosphate bioceramics is based on HAp, β-TCP, α-TCP and/or biphasic calcium phosphate (BCP), which is an intimate mixture of either β-TCP - HAp [94-100] or α-TCP - HAp [101-111]. The preparation technique of these calcium phosphates has been extensively reviewed in literature [1, 4, 37, 102-104]. When compared to both β- and α-TCP, HAp is a more stable phase under physiological con‐ ditions, as it has a lower solubility (Table 1) [37, 109-110]. Therefore, the BCP concept is de‐ termined by the optimum balance of a more stable phase of HAp and a more soluble TCP. Due to a higher biodegradability of the β - or α -TCP component, the reactivity of BCP in‐ creases with the TCP-HAp the increase in ratio. Thus, in vivo bioresorbability of BCP can be controlled through the phase composition [95]. As implants made of calcined HAp are found in bone defects for many years after implantation, bioceramics made of more soluble calcium phosphates is preferable for the biomedical purposes [94-110]. HAp has been clini‐ cally used to repair bone defects for many years [3]. However, Hap has poor mechanical properties [3]. Their use at high load bearing conditions has been restricted due to their brit‐ tleness, poor fatigue resistance and strength.

The main reason behind the use of β-TCP as bone substitute materials is their chemical similarity to the mineral component of mammalian bone and teeth [1-3]. The application of tricalcium phosphate as a bone substitute has received considerable attention, because it is remarkably biocompatible with living bodies when replacing hard tissues and be‐ cause it has biodegradable properties [1-29]. Consequently, β-TCP has been used as bone graft substitutes in many surgical fields such as orthopedic and dental surgeries [3, 11-12, 16-17]. This use leads to an ultimate physicochemical bond between the implants and bone-termed osteointegration. Even so, the major limitation to the use of β-TCP as loadbearing biomaterial is their mechanical properties which make it brittle, with poor fati‐ gue resistance [3, 10, 21-29]. Moreover, the mechanical properties of tricalcium phosphate are generally inadequate for many load-carrying applications (3 MPa – 5 MPa) [3, 10, 20-29]. Its poor mechanical behaviour is even more evident when used to make highly porous ceramics and scaffolds. Hence, metal oxides ceramics, such as alumina (Al2O3), ti‐ tania (TiO2) and some oxides (e.g. ZrO2, SiO2) have been widely studied due to their bioi‐ nertness, excellent tribological properties, high wear resistance, fracture toughness and strength as well as relatively low friction [19, 21-22, 29-31]. However, bioinert ceramic ox‐ ides having high strength are used to enhance the densification and the mechanical prop‐ erties of β-TCP. In this chapter, we will try to improve the strength of β-TCP by introducing a bioinert oxide like alumina. This is because there are few articles reporting the toughening effects of an inert oxide (like alumina (Al2O3)) on the mechanical proper‐ ties of β-TCP [22, 27, 29]. Alumina has a high strength and is bio-inert with human tis‐ sues [19, 22, 27, 29]. In order to improve the biocompatibility of alumina and the strength of tricalcium phosphate effectively, and in order to search for an approach to produce high performances of alumina-tricalcium phosphate composites, β-TCP is intro‐ duced with different percentages in the alumina matrix. The aim of our study is to elabo‐ rate and characterize the TCP-Al2O3 composites for biomedical applications.

This chapter proposes to study the sintering of the alumina-tricalcium phosphate compo‐ sites at various temperatures (1400°C, 1450°C, 1500°C, 1550°C and 1600°C) and with differ‐ ent percentages of β-TCP (10 wt%, 20 wt%, 40 wt% and 50 wt%). The characterization of biomaterials will be realized by using dilatometry analysis, differential thermal analysis (DTA), X-ray diffraction (XRD), magic angle spinning nuclear magnetic resonance (MAS NMR), scanning electron microscopy analysis (SEM) and by using the mechanical proper‐ ties, such as rupture strength (σr) of these biomaterials.
