**1. Introduction**

46 Biomaterials – Physics and Chemistry

Biomaterial Implantation in Facial Esthetic Diseases: Ultrasonography Monitor Follow-Up

Journal of Craniofacial Surgery –Vol.19, N. 4 -July 2008

Elena Indrizzi, MDS, Luca Maria Moricca, MD, Valentina Pellacchia, MD, Alessandra Leonardi, MD, Sara Buonaccorsi, MD, Giuseppina Fini, MDS, PhD. The

> Biomaterials are based on a broad range of materials, such as organic polymers, metals and ceramics including both sintered and chemically bonded ceramics (silicates, aluminates, sulphates and phophates). The biomaterials can be made prior to use in the body in a conventional preparation of the material. The need for in situ in vivo formed implant materials makes the chemically bonded ceramics especially potential as biomaterials. These ceramics include room/body temperature formed biomaterials with excellent biocompatibility. Ca-aluminate as a biomaterial has been evaluated for over two decades with regard to general physical, mechanical and biocompatible properties. The Caaluminate based materials exhibit due to their unique curing/hardening characteristics and related microstructure a great potential within the biomaterial field. The presentation in this chapter aims at giving an overview of the use of Ca-aluminate (CA) as a biomaterial within odontology, orthopaedics and as a carrier material for drug delivery. The examination deals with aspects such as; the chemical composition selected, inert filler particles used, early properties during preparation and handling (working, setting, injection time, translucency, radio-opacity), and final long-term properties such as dimensional stability and mechanical properties (fracture toughness, compressive and flexural strength, hardness and Young´s modulus). One specific topic deals with the sealing of the Ca-aluminate biomaterials to tissue - a key in the understanding of the mechanisms of nanostructural integration.

### **2. Overview of properties of chemically bonded ceramics**

The Ca-aluminate bioceramics belong to the chemically bonded ceramics, which are usually presented or known as inorganic cements (Mangabhai, 1990). Three different cement systems – Calcium phosphates (CP), Calcium aluminates (CA) and Calcium silicates (CS) are discussed in some details in this section. Ceramic biomaterials are often based on phosphate-containing solubable glasses, and various calcium phosphate salts (Hench, 1998). These salts can be made to cure *in vivo* and are attractive as replacements for the natural calcium phosphates of mineralised tissues. The Ca-phosphate products are gaining ground in orthopaedics as resorbable bone substitutes. Biocements are often based on various calcium phosphate salts – sometimes in combination with Ca-sulphates (Nilsson, 2003). These salts can be made to cure *in vivo* and are attractive as replacements for the natural

Nanostructural Chemically Bonded Ca-Aluminate Based Bioceramics 49

Fig. 1. The phase diagram of the high-strength bioceramic cements (Muan and Osbourne,

*Stable cements - CA* 

the mono Ca-aluminate, CaOxAl2O3 - the reaction at above 30 oC is described using cement

 3 (CaAl2O4) + 12 H2O Ca3(Al(OH)4)2(OH)4 + 4 Al(OH)3 (2) This example demonstrates 1) the phases obtained, C3AH6 (katoite) and AH3 (gibbsite), and 2) the amount water consumed in the reaction. The technological importance of this is that all the water needed for paste like consistency or injectability can be consumed in the formation of solid phases yielding products with low porosity, one of the requirements for high strength. As can be seen in Eq. (1) three CaAl2O4 units consume twelve water molecules during hardening. This can be compared with the hardening of Calcium Phosphate Cement (CPC) where practically no extra water is consumed. In the case of CPC, the reaction liquid is only used as a vehicle for the reaction to take place. In both cases the hardening and formation of a solid body are driven by the precipitation of small hydrates, nano-size crystals of katoite and gibbsite for CA, and apatite or brushite for CPC. The amount required water is as high as 28% for CA. The water content of apatite, Ca5(PO4)3OH, or 10CaOx3P2O5 H2O (C10P3H) is 2%. The CPC-system may contain some additional Casulphate which can pick up some extra water. An additional 30 % Gypsum, CaSO4 ½ H2O to

The rate of the hydration is controlled by 1) the cement phase, 2) the particle size of the cement, 3) the hydration temperature and 4) processing agents including especially accelerators. Typical powder composition data for CA-cements as biomaterials are shown in

3CA + 12H C3AH6 + 2AH3 (1)

*Sintered inert ceramics* 

*- AS* 

1965)

Or

chemical abbreviation as (Mangabhai, 1990);

*Slowly resorbable cements - CS* 

the CPC-system yields approximately a total water content of 6%.

mineralised tissues. However, these products have low compression strength values - in the interval 10-40 MPa - and are therefore questioned as load bearing implants.

Materials based on Ca-aluminate (CA) and Ca-silicate (CS) with chemistry similar to that of Ca-phosphates (CP) contribute to some additional features of interest with regard to dental and orthopaedic applications (Scriviner, 1988). The inherent difference in water uptake between the CA/CS-systems and CP gives benefits as:


Materials based on Ca-aluminate and Ca-silicate thus contribute to some additional features of interest with regard to dental and orthopaedic applications. These features are related to the high amount of water involved in the curing process, the early and high mechanical strength obtained, and the biocompatibility profile including *in situ* reactions with phosphates ions of the body fluid. Compressive strength of cements based on Ca-silicate and Ca-aluminate is in the range 50-250 MPa depending on the water to cement ratio. The mechanical properties tested for the three Ca-based cement systems are compiled in Table 1 (Kraft, 2002, Loof et al 2003, Engqvist et al 2006).


Table 1. Mechanical property profile of the Ca-aluminate, Ca-silicate and Ca-phosphate systems

The water content involved in the hydration of the different chemically bonded ceramics are presented in Table 2.


Table 2. The three chemically bonded ceramic systems most used for biomaterials

#### **2.1 Materials and basic function**

#### **2.1.1 Main chemistry**

The injectability and handling features of the chemically bonded ceramics is mainly caused by the added water as the reacting phase with the powdered cements. This reaction is an acid-base reaction where water acts as a weak acid and the cement powder as a base. Several cement phases exist in the CaO - Al2O3 (CA) and in the CaO-SiO2 (CS) systems, see Figure 1, but only a few are suitable as injectable materials. For one of the most attractive phases –

Fig. 1. The phase diagram of the high-strength bioceramic cements (Muan and Osbourne, 1965)

the mono Ca-aluminate, CaOxAl2O3 - the reaction at above 30 oC is described using cement chemical abbreviation as (Mangabhai, 1990);

$$\text{C}\begin{array}{cccc} \text{C}\text{A} & + & 12\text{H} & \rightarrow & \text{C}\_{3}\text{AH}\_{6} \text{ + } 2\text{AH}\_{3} \text{ } & & & \text{(1)} \end{array}$$

Or

48 Biomaterials – Physics and Chemistry

mineralised tissues. However, these products have low compression strength values - in the

Materials based on Ca-aluminate (CA) and Ca-silicate (CS) with chemistry similar to that of Ca-phosphates (CP) contribute to some additional features of interest with regard to dental and orthopaedic applications (Scriviner, 1988). The inherent difference in water uptake

Materials based on Ca-aluminate and Ca-silicate thus contribute to some additional features of interest with regard to dental and orthopaedic applications. These features are related to the high amount of water involved in the curing process, the early and high mechanical strength obtained, and the biocompatibility profile including *in situ* reactions with phosphates ions of the body fluid. Compressive strength of cements based on Ca-silicate and Ca-aluminate is in the range 50-250 MPa depending on the water to cement ratio. The mechanical properties tested for the three Ca-based cement systems are compiled in Table 1

Ca-silicate based

Ca-phosphate based material

hydrated product

> 60 Approx 25

> 30 Approx 20

material

based material

The water content involved in the hydration of the different chemically bonded ceramics are

Apatite 10CaO 3P2O5 H20 7 Approx 5

System Typical phase(s) Oxide formula Mol % H2O Weight-% in

+ Al2O3 2H2O

Table 2. The three chemically bonded ceramic systems most used for biomaterials

5CaO 6SiO2 5H2O + Ca, Si)H2O

The injectability and handling features of the chemically bonded ceramics is mainly caused by the added water as the reacting phase with the powdered cements. This reaction is an acid-base reaction where water acts as a weak acid and the cement powder as a base. Several cement phases exist in the CaO - Al2O3 (CA) and in the CaO-SiO2 (CS) systems, see Figure 1, but only a few are suitable as injectable materials. For one of the most attractive phases –

Compressive strength (MPa) 100-200 100-150 < 100 Flexural strength (MPa) 30-60 30-40 20-30 Young´s modulus (GPa) Approx. 15 Approx. 11 Approx. 3 Table 1. Mechanical property profile of the Ca-aluminate, Ca-silicate and Ca-phosphate

interval 10-40 MPa - and are therefore questioned as load bearing implants.

between the CA/CS-systems and CP gives benefits as:

Tuneable handling properties, e.g. rheology.

(Kraft, 2002, Loof et al 2003, Engqvist et al 2006).

Property profile after 7 days Ca-aluminate

Ca-aluminate Katoite + gibbsite 3CaO Al2O3 6 H20

amorphous phases

Ca-silicate Tobermorite +

**2.1 Materials and basic function** 

**2.1.1 Main chemistry** 

Possibility to add fillers, e.g. for improved radio opacity.

Higher mechanical strength.

systems

Ca-

phosphate

presented in Table 2.

$$\text{3 (CaAl\_2O\_4)} + 12 \text{ H\_2O} \rightarrow \text{Ca(Al(OH)\_4)\_2(OH)\_4} + 4 \text{ Al(OH)\_3} \tag{2}$$

This example demonstrates 1) the phases obtained, C3AH6 (katoite) and AH3 (gibbsite), and 2) the amount water consumed in the reaction. The technological importance of this is that all the water needed for paste like consistency or injectability can be consumed in the formation of solid phases yielding products with low porosity, one of the requirements for high strength. As can be seen in Eq. (1) three CaAl2O4 units consume twelve water molecules during hardening. This can be compared with the hardening of Calcium Phosphate Cement (CPC) where practically no extra water is consumed. In the case of CPC, the reaction liquid is only used as a vehicle for the reaction to take place. In both cases the hardening and formation of a solid body are driven by the precipitation of small hydrates, nano-size crystals of katoite and gibbsite for CA, and apatite or brushite for CPC. The amount required water is as high as 28% for CA. The water content of apatite, Ca5(PO4)3OH, or 10CaOx3P2O5 H2O (C10P3H) is 2%. The CPC-system may contain some additional Casulphate which can pick up some extra water. An additional 30 % Gypsum, CaSO4 ½ H2O to the CPC-system yields approximately a total water content of 6%.

The rate of the hydration is controlled by 1) the cement phase, 2) the particle size of the cement, 3) the hydration temperature and 4) processing agents including especially accelerators. Typical powder composition data for CA-cements as biomaterials are shown in

Nanostructural Chemically Bonded Ca-Aluminate Based Bioceramics 51

However, the final strength and in the case of dental applications the translucency (Engqvist

It should be noted that for CBC materials, irrespective of chemistry (CA, CS or CPC), the final porosity cannot be zero. When the hydrates precipitate there is a contraction of approximately 10 %. The porosity is in the nanometer range and its exact amount is difficult to determine, but < 10 % of the filled space (the original liquid-phase volume) is estimated to be pores. However, this internal shrinkage related to hydration and precipitation yield no total shrinkage of the bulk material. In contrast, a limited expansion close to zero, may be induced (Kraft 2002). The porosity lowers the mechanical strength (although being in the nanometer range) but also enables liquids to diffuse into, or even through, the hardened CBC materials. This is an important feature when release of loaded drugs is a

Ca-aluminates comprise double oxides of CaO and Al2O3. Several intermediate phases exist and these are - using the cement chemistry abbreviation system - C3A, C12A7, CA, CA2 and CA6, where C=CaO and A=Al2O3. See Fig. 1 above. Table 5 presents typical property data.

Property Typical value Interval\* Compression strength, MPa 150 60-270 Young´s modulus, GPa 15 10-20 Thermal conductivity, W/mK 0.8 0.7-0.9 Thermal expansion, ppm/K 9.5 9-10 Flexural strength, MPa 50 20-80 Fracture toughness, MPam1/2 0.5 0.3-0.8

Radio-opacity, mm 1.5 1.4-2.5 Process temperature, oC > 30 30-70 Working time, min 3 < 4 Setting time, min 5 4-7 Curing time, min 20 10-60 Porosity after final hydration, % 15 5-60

The interval is primarily related to the c/w ratio used, and the highest values are achieved with c/w

Table 5. Mean property data of dental Ca-aluminate based materials (Kraft 2002, Lööf 2008,

Due to reduced porosity based on the huge water uptake ability, the Ca-aluminate material exhibit the highest strength among the chemically bonded ceramics. The inherent flexural strength is above 100 MP based on measurement of the fracture toughness, which is about 0.7 - 0.8 MPam1/2. The actual flexural strength is controlled by external defects introduced during handling and injection of the material. The thermal and electrical properties of Caaluminate based materials are close to those of hard tissue, the reason being that Caaluminate hydrates chemically belong to the same group as Ca-phosphates, the hard tissue

< 0.01 -

et al 2004), are reached after approximately a few days maturing.

**3. Ca-aluminate – general description and property profile** 

Corrosion resistance, water jet impinging, reduction in

ratio close to that of complete hydration with no excess of water

Lööf et al 2004,2005, Hermansson et al 2008)

mm

complementary aspect of the injectable biomaterial.

Table 3. Zirconia or high-density glasses are added for achievement of increased strength and increased radio-opacity. The glasses are used preferentially in dental applications where translucency is an additional desired feature. The high radiopacity of zirconia or other heavy-element containing phases means that the physician during the injection can follow the paste penetration in bone tissue without risking any possible leakage of the material into the surrounding tissue.


Table 3. Typical composition of an injectable biomaterial cement powder.

Typical processing agents are accelerators/retarders, dispersants, viscosity agents to control reaction rate, temperature and the cohesiveness, and in general the rheology. Examples are lithium chloride, polycarboxylate polymers and cellulose, as well as glass poly-alkeonates. For the CS-system Ca-chloride at high concentrations is normally used as an accelerator. For cements as injectable biomaterials, the reaction rate must be controlled with respect to working time, setting time, curing time and the maximum temperature during hydration. Typical data are presented in Table 4. The cement reactions are all exothermic and the temperature raise is controlled by the specific cement phase selected, and the hydration rate and the amount of material injected. For dental application the temperature raise is limited to a few oC above 37 oC. For orthopaedic applications where larger amounts (2-10 cm3) are used the temperature raise is more pronounced but lower than that of the conventional PMMA-based materials (Lewis, 2006).


Table 4. Typical working and setting times and maximum reaction temperature of the systems discussed.

The on-going precipitation of hydrates and the reduction of the amount of liquid phase result in the formation of a material skeleton. This repeating reaction is fast at the beginning, resulting in a hardened product within 4-20 minutes depending on intended application. Strength corresponding to load carrying capacity is reached after approximately one hour.

Table 3. Zirconia or high-density glasses are added for achievement of increased strength and increased radio-opacity. The glasses are used preferentially in dental applications where translucency is an additional desired feature. The high radiopacity of zirconia or other heavy-element containing phases means that the physician during the injection can follow the paste penetration in bone tissue without risking any possible leakage of the material into

(wt-%)

Mean particle

size

Max reaction temperature,

(for dental applications <

oC

40)

< 10 <50 nm

Compound Formula Function Amount

Table 3. Typical composition of an injectable biomaterial cement powder.

µ-Silica SiO2 Expansion and

PMMA-based materials (Lewis, 2006).

System Working time at 23 oC, min

systems discussed.

Ca-aluminate CaOxAl2O3 Cement binder 50-70 < 5 m

ZrO2 Radiopacier 20-40 < 1 m

Setting time at 37 oC,

min

Table 4. Typical working and setting times and maximum reaction temperature of the

The on-going precipitation of hydrates and the reduction of the amount of liquid phase result in the formation of a material skeleton. This repeating reaction is fast at the beginning, resulting in a hardened product within 4-20 minutes depending on intended application. Strength corresponding to load carrying capacity is reached after approximately one hour.

Ca-aluminate Approx. 5 8-12 < 60,

Ca-silicate Approx. 10 15-18 < 45 Ca-phosphate 5 10-12 < 40 PMMA 5-10 11 < 90

viscosity controller

Typical processing agents are accelerators/retarders, dispersants, viscosity agents to control reaction rate, temperature and the cohesiveness, and in general the rheology. Examples are lithium chloride, polycarboxylate polymers and cellulose, as well as glass poly-alkeonates. For the CS-system Ca-chloride at high concentrations is normally used as an accelerator. For cements as injectable biomaterials, the reaction rate must be controlled with respect to working time, setting time, curing time and the maximum temperature during hydration. Typical data are presented in Table 4. The cement reactions are all exothermic and the temperature raise is controlled by the specific cement phase selected, and the hydration rate and the amount of material injected. For dental application the temperature raise is limited to a few oC above 37 oC. For orthopaedic applications where larger amounts (2-10 cm3) are used the temperature raise is more pronounced but lower than that of the conventional

the surrounding tissue.

Zirconium dioxide

However, the final strength and in the case of dental applications the translucency (Engqvist et al 2004), are reached after approximately a few days maturing.

It should be noted that for CBC materials, irrespective of chemistry (CA, CS or CPC), the final porosity cannot be zero. When the hydrates precipitate there is a contraction of approximately 10 %. The porosity is in the nanometer range and its exact amount is difficult to determine, but < 10 % of the filled space (the original liquid-phase volume) is estimated to be pores. However, this internal shrinkage related to hydration and precipitation yield no total shrinkage of the bulk material. In contrast, a limited expansion close to zero, may be induced (Kraft 2002). The porosity lowers the mechanical strength (although being in the nanometer range) but also enables liquids to diffuse into, or even through, the hardened CBC materials. This is an important feature when release of loaded drugs is a complementary aspect of the injectable biomaterial.
