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Journal of Materials Science and Engineering A 3 (7) (2013) 467-474

DAVID

PUBLISHING

Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute Manal Mostafa Awad1, Medhat Abdelmonem El-Messiery1 and Mohamed Bahgat El Kholy2 1. Engineering Physics Department, Faculty of Engineering, Cairo University, Egypt 2. National Center of Research (NCR), Ceramics Unit, Cairo, Egypt Received: April 18, 2013 / Accepted: May 16, 2013 / Published: July 10, 2013. Abstract: In this paper, a study was carried out to produce calcium phosphate ceramics whose composition comes close to that of natural dry bone. Dicalcium phosphate dehydrated (CaHPO4·2H20) and calcium carbonate (CaCO3) were mixed at different proportions so that three batches of ceramics whose Ca/P ratio are 1.5, 1.7 and 1.9 are obtained. These ratios lie in close vicinity to the reported data for dry cortical bone (Ca/P = 1.67). Sintering was carried out at temperatures ranging from 1,100 °C to 1,350 °C. The variation in batch composition as well as in sintering temperature has proved to play a decisive role in determining the end product characteristics. Parameters such as bulk density, porosity, firing shrinkage, modulus of mechanical rupture, mineralogical and textural features behavior, were studied to assess their matching with those of human cortical bone. Key words: Bone ceramic substitute, Ca/P ratio, mechanical properties.

1. Introduction Biomaterials are one of the progressively developed interdisciplinary sciences, which attract the attention of engineers, chemists, medical practitioners among other investigators. Perhaps metals (stainless steel, titanium alloy and cobalt-chrome alloy) were first introduced as bone prostheses but many materials and composites offer better biocompatibility. Polymers such as polyethylene, poly-tetrafluoroethylene (teflon, PTFE), polyvinylchloride (PVC), polyurethanes, polypropylene, silicone rubber and poly-methylrnethacrylate have proven their better compatibility in connection with hard tissues as bone, dental applications and bone cement. Bioglass, are introduced commercially for some types of orthopedic implants. Composites such as carbon fiber reinforced resins are used as artificial ligaments. Ceramics offer good chemical and corrosion Corresponding author: Manal Mostafa Awad, associate professor, research fields: biomedical physics and engineering. E-mail: [email protected].

resistant properties, they withstand considerable compressive stress. Moreover, they are generally, attractive biologically because of their inertness, non-toxicity and high wear resistance. Among currently used bioceramics are the high purity Alumina ceramics; they are considered as highly bioinert implants and offer excellent mechanical response. Calcium phosphate [1] based implants are another group of ceramics which acquire an increasing importance as a biomaterial for dental or orthopedic applications. The interest given to calcium phosphate salts is due to their evident existence as the mineral phase in bone. Calcium phosphate ceramics are considered highly biocompatible [2-5] when implanted; they are not only acceptable by the body but also introduced in either biodegradable or bioactive form. Their implantation in connection with bones usually leads to some sort of long term integration between the implant and the biological environment which is one of utmost aims of biomaterial sciences.

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Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

Various types of calcium phosphate bioceramics, such as hydroxyapatite tricalcium phosphate [6], have successfully produced positive results not only in bone regeneration but also as a mean of drug delivery. Also, porosity has been introduced by different techniques and their biological significance has been positively established.

Bioceramics

consisting

of

calcium

phosphate were introduced and recommended as bone replacement. Hydroxyapatite (CaPO4) ceramics are used for bone grafts and dental filling also it is used for coating the metal surgical implants (most often made of titanium and its alloys, or stainless steel). Bioactive ceramics are the best candidate for bone substitute, they have excellent biocompatibility and close physical properties to the tissue being replaced or repaired. One of the great advantages of using calcium phosphate ceramics is its biological compatibility; the effect of porosity up to an average pores size of about 500 μm [7-9], induce bone ingrowth. However, bioceramics are generally, extremely brittle; suffer from poor machinability and susceptible to stress-dependent reactions with the environment. Carbon fiber reinforced bioceramics [10] was reported to improve the mechanical properties of the implant. The present work addresses the effects of Ca/P ratio and the sintering temperature on the final production of calcium phosphate ceramics. It aims to examine how this ratio improves the structure and the physical properties of the bioceramics and how much it brings it closer to human bone.

2. Materials and Methods: There are different procedure to produce hydroxyapatite bioceramics [11-13]. We used analytical grades, (Merck) dicalcium phosphate dehydrate (CaHPO4·2H2O) and calcium carbonate (CaCO3) powders. Different percentages, as shown in Table 1, were mixed in order to control the Ca/P ratio in the batches produced. The Ca/P ratio referred to in this text means the ratio of the atomic proportions of

Table 1 Three calcium phosphate ceramic batches of different Ca/P ratio were used. Batch No. 1 2 3

Ca/P ratio 1.5 1.7 1.9

CaHPO4·2H2O (%) 77.5 71.1 65.6

CaCO3 (%) 22.5 28.9 34.4

Ca and P in the fired batches. This ratio is calculated from weight percentages of CaO and P2O5 of basic composition of the batch so that: Ca P

Wt% of CaO /56 Wt% of P O /71

Processing and examination: 500 g of each batch was prepared in the form of aqueous slurry of 55% water content, the latter was then vigorously stirred for 2 h to ensure a uniform and homogeneous distribution of batch’s ingredients. After sufficient time, careful decantation of the supernatant was carried out and then the slurry was dried in an oven dryer at 60 °C for 24 h. The temperature was then lifted up 110 °C for 24 h. Test specimens in the form of discs (25 mm diameter and 5 mm thickness) as well as bars of (70 × 10 × 5 mm) were shaped by the dry press method using hardened steel mould at a static pressure of 3.43 × 1011 N/m2. To facilitate the shaping process, 7% of the basic composition by weight, of either polyvinyl alcohol, glycerol or starch solution (5% concentration), were used as binders. The test specimens were then kept in an enclosure to eliminate possible moisture effects until the firing process was reached. Firing was conducted at different temperatures ranging from 1,100 °C to 1,350 °C with 50 °C intervals. Alumina Silicate sagar was used to ensure that the temperature will be uniform for all specimens. The firing rate chosen was 150 °C/h with soaking period of 2 h at the top temperature. The fired samples have been cooled down to room temperature. Sintering parameters such as apparent porosity and bulk density were determined on the disc shaped specimens by the fluid displacement method according to the ASTM specifications (C-372-72). Mechanical strength in the form of the modulus of

469

Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

were coated with a thin film of gold of about 200 A thick. Uniform coating was obtained under vacuum with a sputter coater type [S150, Edwards& England]. The magnification chosen was 2,000, working distance 20 mA and accelerating voltage 25 KV.

the three batches increases with the firing temperature and has an apparent peak at 1,300 °C. Fig. 3 shows the variation of the percentage of apparent porosity. Unlike the previous obtained results in Figs. 1 and 2, the bulk density for the three batches decreases with firing temperature with a minimum value at 1,300 °C for both batches II and III. Firing shrinkag %

12 10 8 6 4

Batch I

2

1100

Fig. 1

1150

1200

1250

1300

1350

The temperature versus and the firing shrinkage.

2.5 2 1.5

The effect of the firing temperature on the physical 1 0.5

Batch I BatchII Batch III Temperature °C

0 1100

Fig. 2

1150

1200

1250

1300

1350

The temperature versus the bulk density .

40 Apparent porosity %

that the temperature is uniformed for all samples. The firing schedule was 150 °C/h with soaking period of 2 h at the higher end of the temperature range (1,350 °C). Fig. 1 shows the relationship between the linear firing shrinkage for the three Ca/p ratios, as the firing temperature increases, so the linear firing shrinkage increases nonlinearly. The results exhibit a peak at 1,300 °C. Fig. 2 exhibits the change of firing temperature on the bulk density, one can see that the bulk density for

Batch III

0

3. Results and Discussion properties (firing shrinking, bulk density and apparent porosity) are reported. Three batches of different Ca/P ratio were studied. The specimens were fired at temperatures from 1,100 °C to 1,350 °C. The firing was conducted in an electrically heated chamber furnace. Aluminosilicate sagger was used to ensure

Batch II

Temperature °C

Bulk density g/cm3

rupture was conducted on the bar in which the specimen is subjected to the three-points loading technique. The main crystalline phases present after sintering were determined by the powder X-ray diffraction (XRD) analysis using CuK-radiation. A Philips X-ray diffractometer, type PW 2256/00, was employed. After firing, powder samples, consisting of randomly oriented aggregates of the investigated batches were prepared. The powder samples were spread as a flat specimen fitted to the sample holder. A scanning speed of 2° per min and a paper speed of 1 cm/min were chosen. A scanning electron microscope model (Jeol, JSM-T 200, resolution 70 nm, magnification up to 100,000); was used for both ceramic and bone samples. They

30 20 10

BatchIII BatchII BatchI Temperature in oC

0 1100

Fig. 3

1150

1200

1250

1300

1350

The temperature versus the apparent porosity.

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Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

Fig. 4 shows that the water absorption follows similar features to that of apparent porosity. The water absorption declines with firing temperature. Actually this is expected since the decrease in porosity of the sample should lead to a corresponding decrease in the ability of the ceramics to absorb water within its structure. The above figures can be explained as follows; during sintering, the particles, in their initial powder form, are brought into close contact and the porosity is reduced. The atoms, in small grains, are thus transferred to larger ones and open pores are gradually replaced by solid material. This mass transfer would create some closed pores which, on further heating, lead to bloating effects (i.e., reduction in the bulk density). The expansion of residual gases and the evolution of a gaseous decomposition product may have a substantial effect. Moreover, the four physical parameters showed in Figs. 1-4, exhibit apparent dependence on the Ca/P ratio (i.e., on the amount of CaCO3 present). This dependence can be attributed to the variation in the amount of the CO2 gas evolved as a result of the decomposition product of CaCO3. The bulk density, as well as the firing shrinkage, follow similar pattern while the apparent porosity follow opposite trend to both parameters. Fig. 5 exhibits the relationship between the modulus of rupture, MOR and the firing temperature. The MOR of each batch increases with firing temperature reaching a peak at about l,300 °C, which is the same for the three batches regardless of their Ca/P ratio. But the increase of the Ca/P ratio reduces MOR, which is fundamentally expected from the observed increase of apparent porosity. It is known that the starch can increase the porosity as a result of its decomposition at temperature higher than l,350 °C. In the present case, it exists at a low percentage of 0.35%. Therefore, we expect that the existence of calcium carbonate is the main source of observed CO2.

Fig. 4

The temperature versus the water absorption.

Fig. 5

The temperature versus MOR.

Full comparison of the results obtained at firing temperature of 1,300 °C reveals that the basic change in calcium phosphate salts (from tricalcium phosphate to hydroxyapatite) leads to an increase in porosity and to a decrease in the MOR, linear firing shrinkage and density. It is noteworthy that mineralogical evidence has indicated that β-whitlockite mineral can be transformed into hydroxyapatite when presented in physiological media. This means that sintered calcium phosphate of small Ca/P ratio when implanted in a living tissue would release Ca2+ as well as (HPO4) 2-. The release of these ions result in a decrease in the pH of the surrounding physiological medium. This in turn leads to dissolution of the thin layer of surface hydroxyapatite causing a further lowering in pH value. Eventually a complete biodegradation of the

Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

tricalcium phosphate implant is achieved. Besides, there is strong evidence which suggests that tricalcium phosphate ceramics dissolve 12 to 22 times faster than a substitution of a fully dense hydroxyapatite ceramics. X-ray diffraction patterns of the three batches are displayed in Fig. 6. The three batches ere sintered at 1,300 °C. The identification has been worked out using ASTM standard cards. It has been found that, batch No.1 (Ca/P = 1.5) consists entirely of β-tricalcium phosphate (β-whitlockite mineral, β-Ca3(PO4)2). But for batch 2 (Ca/P = 1.7) and batch 3 (Ca/P = 1.9), respectively, the composition is mainly hydroxyapatite (Ca10(PO4)6(OH)2). A slight shift in the peak position of the hydroxyapatite is found to take place with the increase in Ca/P ratio; this may be attributed to the possible increase in the cell volume due to the formation of a solid solution. The formation of β-Tricalcium phosphate at Ca/P = 1.5 may be explained on stoichiometric basis in accordance to the following chemical reactions: 2 CaHPO 2H O

CaCO CaCO

2 CaHPO

4H O

CaCO CaCO

2 Ca P O

CaHPO

CaCO

T

Ca P O H O Ca PO

β

CO

Formation of hydroxyapatite at Ca/P = 1.5 is in full agreement with some data previously reported [14], many investigators believe that hydroxyapatite can be highly stable upon sintering and retain its water contents even at temperatures up to 1,400 °C. Some workers, on the other hand, claim that there is a partial dehydroxylation at temperature above 1,000 °C. As a result, the mineral oxyhydroxyapatite is formed according to the following formula. Ca PO OH 2x O ( = vacancy and x > 1)

x

471

Fig. 6 X-ray diffractograms of experimental batches fired at 1,300 °C.

In this case, vacancies are located in the hydroxyl sites. Accordingly, it seems that the pronounced bloating effect observed at 1,300 °C in batches 2 and 3, is correlated directly to the partial dehydroxylation of hydroxyapatite present. The scanning electron micrographs, shown in Fig. 7, reveal distinguishable variation in the textural characteristics of the different ceramic batches. Apparent increase in the pore content is produced as a result of the increase in the Ca/P ratio from 1.5 to 1.9. The β-whitlockite sample, show a greater grain growth than the other two hydroxyapatite samples (Batches 2 and 3. Geometrically, β-whitlockite grains appear to have relatively sharp edges while the two other Hydroxyapatite batches show rounded edges and necks closed pores of rounded shapes are predominant in batch I with an average size of 2 μm; while batch II, in contrast, shows irregular connected pores attaining an average size of 4 μm. Larger connected pores of about 8 μm are shown in batch III which also exhibits pores of a mean size of about 1 μm.

472

Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

Batch I

Batch II

Batch III

(a)

(b)

Fig. 7 The comparison between living cortical bone and bone ceramics of different batchs, (a) natural cortical bone and (b) bone ceramic substitute.

Batch I (Ca/P = 1.5) possesses, however, the lowest expansion coefficient (10.8 × 1 -6 cm/°C ), whereas the other two batches 2 and 3 have a higher value of about (12.8 × 1-6 cm/°C). This could be attributed to the

difference in the coordination number (packing factor) of the various crystallographic phases. Densely packed phases have a greater thermal expansion than those with more open packed structure19

Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

4. Conclusions It is highly evident that the variation of Ca/P ratio has significant effects on cellular growth within the implant [15, 16]. Varying Ca/P ratio leads to significant differences in the physical, mechanical and mineralogical characteristics of the end products. An increase of that ratio from 1.5 to 1.9, results in an increase in the porosity and the thermal expansion, and in a decrease in the density, firing shrinkage and mechanical strength. X-ray diffraction analysis indicates that at Ca/P = 1.5, the only polycrystalline phase produced is β-whitlockite while Hydroxyapatite mineral is the only crystalline phase identified in both batches of Ca/P = 1.7 and 1.9. The substantial bloating effect observed at 1,300 °C in hydroxyapatite batches, is most probably related to the evolution of H2O as a result of partial dehydroxylation of hydroxyapatite to oxy-hydroxyapatite. Based upon the mechanical considerations, the optimum sintering temperature for all batches was achieved at 1,300 °C. Porosity of bioceramics is considered advantageous since it encourages bone growth and accelerates the rate of biodegradation [17-20]. Yet, the existence of pores reduces the mechanical resistance to stresses hence contributes to the reduction in the modulus of rupture and when the implant is subjected to cyclic loading, the existence of pores throughout the bioceramics would encourage the introduction of micro-cracks leading to fatigue fracture. The bending resistance of ceramics in general is inferior to those of natural dry cortical bone. In the present case the MOR value ranges from 10 to 22 kg/cm2 while this value for bovine is about 1,300 kg/cm2. Therefore, the produced calcium phosphate batches in this work are only biomechanical compatible for applications that require high compressive stresses. In fact, the equivalent bone ceramics would not give the same structure of the cortical bone even if it has the same Ca/P ratio yet the pore size of this bone equivalent comes very near to that of cortical bone hence we can achieve good

473

compatibility in both the composition and pore size and some of the physical parameters.

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Development of Calcium Phosphate Ceramics of Controlled Ca/P Ratio as a Bone Substitute

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