Calcium phosphate and polymer interfaces in orthopaedic cement

clinical Materials 5 (1990) 209-216

Calcium

Phosphate and Polymer Interfaces Orthopaedic Cement

V. Delpech

a

& A. Lebugle

Laboratoire de Physico-chimie des Solides, URA CNRS No. 445, Ecole Nationale Superieure de Chimie, Institut National Polytechnique de TouS.ouse, 38 Rue. des 36 Ponts, 31400 Toulouse, France

ABSTRACT In order to increase the mechanical properties and the bioactivity of surgical cement, the linkage of two monomers, namely hydroxyethylmethacrylate (HEMA) and methylmethacrylate (MMA), by copolymerization to a modified apatite has been studied. This linkage is obtained by grafting an organic molecule containing an ethylenic bond onto the apatite surface. These two studies have shown that after polymerization more than 70% of the modified apatite is irreversibly linked to the polymers. This linkage is due not to an adsorption but to the existence of a stable covalent bond between apatite and polymers. From these results, it should be possible to develop a new orthopaedic cement which will be more biocompatible and will have good mechanical properties.

INTRODUCTION rylic bone cement is commonly used for the stabilization of ostheses in orthopaedic surgery. The cement constitutes the bone-osthesis interface. It is subjected to repeated loads and has to support them. Prosthetic loosening is associated with cemented arthroplasty and is related to the deficiency of mechanical properties and to the lack of a real bond between bone and cement. Research has been carried out to improve the performance of acrylic cement. In order to increase its mechanical properties, several authors Unical Materials 0267-6605/90/$03.50 England. Printed in Northern Ireland

209 0 1990 Elsevier

Science

Publishers

Etd,

210

V. Delpech, A. Lebugle

have studied the influence of different fillers on various mechanical characteristics. The fillers studied were carbon fibres,l-’ Kevlar,8-1” polyethylene fibres,ll metal wire,12,13 and hydroxyapatite.14,15 The mechanical properties are improved by these fillers, but only to a limited extent. According to the authors of this paper, the increase would be more significant if the filler was linked to the organic matrix. Other research has been carried out with the aim of improving bone-cement relation by using bioreactive materials.16 One of these routes consisted of preparing porous acrylic cement to allow bone ingrowth. In our laboratory, recent studies “J* have shown that a particular apatite can be synthesized by grafting an organic molecule containing an ethylenic bond onto the apatite surface. Indeed, in given preparation conditions, the hydroxyethylmethacrylate phosphate (phosphoHEMA) (RPO$-) is bound to non-stoichiometric calcium-phosphate apatite to obtain the following compound:

The bond is formed through the ionized phosphate group which partially replaces the OH- ions located at the apatite tunnel extremity. The carbon chain of phosphoHEMA is sited outside the mineral lattice. This configuration allows it to keep its reactivity, and leads to the formation of crystallites with a thickness ranging between 20 and 30 A. These crystallites are similar to the apatite plaquettes observed in the mineral component of calcified tissues. The introduction of this apatite into the acrylic cement can satisfy both requirements, the improvement of the mechanical properties and the bioreactivity. On the one hand, calcium phosphate is well known for its biocompatibility, and on the other hand the use of the modified form of this compound should allow its linkage to the polymer chain by means of copolymerization. This mineral organic compound should have very good mechanical properties. The study of the linkage between modified apatite and different polymer chains is reported in this paper. This study has been carried out by radical copolymerization of phosphoHEMA apatite compound (AM) with HEMA or methylmethacrylate (MMA). Due to the different kinds of monomers leading to hydrophilic or hydrophobic materials, a particular approach has been used to examine the copolymerization in each case. A parallel study with non-modified apatite (OCPa), Ca8(HP04),.43(P04)3.,,0H,.,,, has been carried out.19

Calcium phosphate and polymer interfaces

MATERIALS

211

AND METHODS

the case of copolymerization with HEMA, the samples were repared by adding a solution containing 500 mg of HEMA and ($02 to a powdery mixture composed of 500 mg of dimethyl-p-toluidine apatite and 0.03 g benzoyl peroxide at room temperature. It is well known that a small quantity of reticulant, ethyleneglycol methacrylate (EGDMA), is contained in HEMA. Its polymerization ads to hydrophilic material which gives a colloid in water. Since the odified apatite and OCPa are completely soluble in acid, it is possib to follow as a function of time the amounts of calcium, of mineral released by acid attack of apatite hosphate and phosphoHEMA ntained in the colloid. After polymerization, the samples were suspended in 500 ml 044 M HClO, solution, and maintained under constant stirring. Solution samples were taken at different times. The amounts of calcium, mineral and organic phosphate” were determined. Thus t amounts of organic phosphate linked to the polymer chains copolymerization could be determined. In the case of copolymerization with MMA, the samples were repared by adding a solution containing 5 ml of MMA and O-1 ml of p-toluidine to a powdery mixture composed of 8 g PM 3 g apatite (AM or OCPa) and 0. hylmethacrylate), enzoyl peroxide at room temperature. In this way PPMA, a hydrophobic material, is formed. Due to t fact that the calcium phosphate included in the polymer matrix can no longer be dissolved by acid, the PMMA solubility in acetone has been used. After polymerization, the samples were stirred and dissolved in 00 ml of acetone. The insoluble part was collected as a powder. The powders were then washed several times with acetone, and analyse for C, H and N and by infrared spectroscopy (IR).

RESULTS As far as copolymerization with HEMA is concerned, the variation as a function of time in the amount of calcium released by acid attack fro copolymers containing modified apatite (curve A) or OCPa (curve shown in Fig. 1. In these two cases, calcium is rapidly extracted 120 hours, and calcium release is nearly 100%. Figure 2 shows the variation as a function of time in the amount of

V. Delpech, A. Lebugle

212

0 curve A

Ca released t

0

Fig.

o curve 0

(%I

Y

50

100

??

Lime (h)

1. Calcium release versus time: curve A, copolymerization modified apatite; curve B, copolymerization

of HEMA with OCPa.

of HEMA

with

mineral phosphate released from copolymers containing either modified apatite (curve A) or OCPa (curve B), and the variation in the relative amount of organic phosphate in the case of modified apatite (curve C). In this case too, the release of mineral phosphate is rapid and almost complete after 120 hours. However, only 30% of organic phosphate contained in modified apatite is extracted. These observations allow us to rule out the assumption that the quantity of organic phosphate released is limited to 30% by insufficient

-_--,.-r curve A

??

curve B 0 curve C

v

I’released (%) IOP

-0

/

/

50

(I

/I / I

tlrne

.

(h)

Fig. 2. Release versus time of mineral phosphate-curve A, copolymerization of HEMA with modified apatite; curve B, copolymerization of HEMA with OCPa-and organic phosphatedurve C, copolymerization of HEMA with modified apatite.

215

Calcium phosphate and polymer interfaces

I.___ 3500

g.

3.

Infrared

3000

1600

1100

1200

1000

600

spectra: curve 1, OCPa; curve 2, insoluble copolymerization of MMA with OCPa.

600

rao

part resulting

CM-~

from

attack. Since the phosphoHEMA is soluble in water, the limite extraction means that 70% of organic phosphate is irreversibly linked to the polymer. the insoluble part of dissolution by FOP. MMA copolymerization, acetone of the copolymer with OCPa presents the same IR spectra (Fi spectra 1 and 2) and identical chemical analysis (Table 1, a and c) initial apatite (OCPa). We can deduce that there are no bon tween OCPa and polymers. In the case of copolymerization with the modified apatite, the C, II, analysis reveals that the carbon content is 4-5 times higher in t ” oluble part than in the initial modified apatite (Table 1, b ore importantly, the IR spectrum shows typical bands of se to those of the modified apatite. Indeed, the -CH vibration nds near 2990 and 2940 cm-‘, 2820 cm-‘, 1450 and 1480 cm-l, 1250cm-l and 1280cm-’ appear and the C===O group band at TABLE1 Results of Carbon Content Determination

of Different Samples Percentage of carbon

(a) (b) (c) (d)

OCPa (octacalcium phosphate) Modified apatite Insoluble part resulting from copolymerization of MMA with OCPa Insoluble part resulting from copolymerization of MMA with modified apatite (e) Modified apatite in suspension in PMMA solution

l-2 2.3 1 13 3

214

V. Delpech, A. Lebugle

I 3500

Fig. 4.

3000

1600

1400

,200

1000

800

600

400

.

CM-

Infrared spectra: curve 1, insoluble part resulting from copolymerization MMA with OCPa; curve 2, modified apatite; curve 3, PMMA.

of

1720 cm-l is much more intense than in the modified apatite. Furthermore, the band at 770 cm-l, due to P-Q-C vibration and missing in the modified apatite, appears after copolymerization (Figure 4, spectra 1, 2 and 3). All these observations show that PMMA fixation takes place exclusively in the case of the modified apatite. Furthermore, the fixation is not due to an adsorption, because it does not take place when the modified apatite is only stirred in an acetone-PMMA solution: in fact, the C, H, N analysis (Table 1, e) and an IR spectrum (Fig. 4, spectrum 2) are the same after treatment as before. It is thus rather obvious that this very strong fixation is due to the copolymerization of the phosphoHEMA apatite compound with MMA.

CONCLUSION Copolymerization experiments of HEMA or MMA with the ethylenic bond of a phosphoHEMA apatite compound show that apatite can be irreversibly linked to various polymer chains. From these results, it should be possible to develop a new orthopaedic cement which will be more biocompatible thanks to the presence of calcium phosphate, and

Calcium phosphate and polymer interfaces

which will have good mechanical bond between filler and matrix.

behaviour

on account

of the

ACKNOWLEDGEMENTS This work was supported by Landanger art of the thesis of Valerie Delpech.

and Bioland

Co. This paper

is

REFERENCES Knoell, A., Maxwell, H. & Bechtol, cement. Ann. Biomed. Eng., 3 (1975) Pilliar, R. M., Blackwell, R., Macnab, reinforced bone cement in orthopedic

C., Graphite

fiber reinforced

bone

225-9.

I. & Cameron, H. U., Carbon fiber surgery. J. Biomed. Mater.

(1976) 893-906.

Pilliar, R. M., Bratina, W. J. & Blackwell, R. A., Mechanical properties of carbon fiber reinforced poly(methylmethacrylate) for surgical implant applications. ASTM Special Technical Publication, STP 636 (1977) 206-27. Pal, S. & Saha, S., Stress relaxation and creep behaviour of normal and carbon fiber reinforced acrylic bone cement. Biomaterials, 3 (1982) 93-9. Robinson, R. P., Wright, T. M. & Burstein, A. H., Mechanical properties of poly(methylmethacrylate) bone cements. J. Biomed. Mater. Res., (1981) 203-S.

Saha, S. & Pal, S., Improvement of mechanical properties of acrylic bone cement by fiber reinforcement. J. Biomech., 17 (1984) 467-78. Saha, S. & Pal, S., Mechanical characterization of commercially-made J. Biomed. Mater. carbon fiber reinforced poly(methylmethacrylate). es., 20 (1986) 817-26.

Wright, T. M. & Trent, P. S., Mechanical properties of aramid fiber reinforcement acrylic bone cement. J. Mater. Sci. Lett., 14 (1979) 503-5. Pourdeyhimi, B., Wagner, H. D. & Schwartz, P., A comparison of mechanical properties of discontinuous Kevlar 26 fiber reinforced bone and dental cements. J. Mater. Sci., 21 (1986) 4468-74. Pourdehimi, B., Robinson, H. H. & Schwartz, P., Fracture toughness of Kevlar 29/poly(methylmethacrylate) composite materials for surgical implantation. Ann. Biomed. Eng., 14 (1986) 277-94. Pourdeyhimi, B. & Wagner, H. D., Elastic and ultimate properties of acrylic bone cement reinforced with ultra-high-molecular-weight polyethylene fibers. J. Biomed. Mater. Res., 23 (1989) 63-80. Taitsman, J. P. & Saha, S., Tensile strength of wire-reinforced bone cement and twisted stainless-steel wire. J. Bone Jt. Surg., 59A (1977) 419-25.

Saha, S. & Kraay, poly(methylmethacrylate) Biomed.

Mater. Res.,

M. J., Improved strength characteristics of beam specimens reinforced with metal wires. /. 13 (1979) 443-57.

216

V. Delpech, A. Lebugle

14. Castaldini,

15.

16. 17.

18. 19.

A. & Cavallini, A., Setting properties of bone cement with added synthetic hydroxyapatite. Biomaterials, 6 (1985) 55-60. Castaldini, A. & Cavallini, A., Creep behaviour of composite bone cement. Biological and Biomedical Performance of Biomaterials, ed. P. Christel, A. Meunier & A. J. C. Lee. Elsevier Science Publishers, Amsterdam, 1986, pp. 525-30. Rijke, A. M., Rleger, M. R., McLaughlin, R. E. & McCoy, S., Porous acrylic cement. J. Biomed. Mater. Res., 11 (1977) 373-94. Subirade, M., Elaboration d’une liaison mineral-organique entre un phosphate de calcium et un monombre phosphoryle. Thesis. INP, Toulouse, 1986. Montel, G., Bone& G., Lebugle, A. dr Subirade, M., Sur la fixation d’ions de grandes dimensions par le reseau cristallin des apatites, et ses consequences biologiques. CR Acad. Sci., 309 (1989) 1155-8. Zahidi, E., Lebugle, A. & Bonel, G., Sur une nouvelle classe de materiaux pour prothbes osseuses ou dentaires. Bull. Sot. Chim. Fr. 4

(1985), 523-7. 20. Lebugle, A., Zahidi, E. & Bonel, G., Realisation

d’un interface mineralorganique comparable a celui de 1’0s par mise en commun de groupements phosphate. Znnov. Tech. Biol. Med., 3 (1982) 626-34.