GB1560992A - Osseous cement - Google Patents

Description

(54) OSSEOUS CEMENT (71) We, THE UNIVERSITY OF VIRGINIA, a corporate body organised under the laws of the State of Virginia, United States of America, of Charlottesville, Virginia 22901, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to osseous cement; such cements have various uses and it is believed that it is possible to formulate osseous cements falling within the scope of the present invention which are suitable for the repair of osseous structures, fixation of implants, and in particular as a dental or orthopaedic cement.

Considerable research effort has been directed to providing cements which have adhesion for, and can be used for repairing human and animal bones or teeth. Although a wide variety of different cement compositions has been proposed for this purpose, the most successful are the acrylic cements, particularly those cements derived from polymers of methyl or ethyl acrylate, or methacrylate.

In the usual method, a metal implant or pin is inserted into the bone which is held in place by the use of a cement which bonds the implant to the adjacent bone. The acrylic monomer cements generally consist of a relatively thick paste or organosol or polymer powder and a low temperature polymerization initiator dispersed into the liquid monomer.

Several difficulties, however, have now been encountered which threaten to significantly hinder the full development of this technique. For one, the polymerization of the acrylic monomer is accompanied by the evolution of considerable amount of exothermal heat which reportedly has been responsible for the development of bone temperatures as high as 83"C using conventional orthopaedic cements. [See for instance, Homsy, C.A., Prosthesis Seating Compounds of Rapid Cure Acrylic Polymers.

National Academy of Sciences-American Academy, Orthopaedic Surgery, Joint Workshop on Total Hip Replacement and Skeletal Attachment (nov. 6, 1969), and Bloch et al, Evaluation of Cold-Curing Acrylic Cement for Prosthesis Stabilization, Clin.

Orthopaedics 72, 239 (1970)].

This high heat evolution has deleteriously resulted in necrosis of the surrounding bone tissue [See Wiltse et al, Expermient Studies Regarding the possible Use of Self-Curing Acrylics in Orthopaedic Surgery. J. Bone Joint Surg. 35A, 961(1957)].

Another difficulty encountered has been the observation that a small amount of unreaced acrylic monomer invariably leaves the bonding area and is released into the general circulatory system. Since the acrylic monomers are quite toxic, even in relatively low concentration, this is now recognized as a considerable difficulty which threatens the continued usage of this technique.

A still further difficulty encountered is that the long-term adhesion of the cement is disappointingly low, so that frequently the implant has been loosened, which resulted in the necessity of further surgical procedures. Methods therefore have been sought to improve the long-term adhesiveness of the cement.

The implant technique for orthopaedic and certain dental procedures was first developed by Charnley, A Biomedical Analysis of the Use Of Cement to Anchor the Femoral Head Prosthesis, J. Bone Joint Surg.

47B 354 (1965). At that time, Charnley recognized that the success of the technique depended upon the smooth transition from the implant to bone through a thin layer of fibrous tissue. If the thin fibrous tissue layer fails to develop, loose prosthesis can occur, which can result in bone erosion or migration.

To overcome this difficulty, it has been attempted to provide means to promote the growth of the fibrous tissue. Several orthopaedic surgeons have attempted to fabricate prosthetic bone implants having a configuration of natural bone, i.e., composed of a network into which the tissue can grow. Incorporating pores in a ceramic material has been successful in that the growth of fibrous tissue and natural bone into the implant can occur. By incorporating pores in ceramic materials, the ingrowth of fibrous tissue followed by ossification has been observed to occur, provided the pores are continuous and large enough to accommodate blood vessels. The resulting bone ingrowth can then rearrange along the stress lines. [See Hulbert et al, Potential of Ceramic Materials as Permanentlv Implantable Skeletal Prosthesis, Second Materials Engineering Conference, National Meeting of AICH.E (1970].

However, all of the currently available implants are pre-formed and thus do not fit exactly into the bones in which they are implanted, necessitating the use of a cement to hold them in place. The previously available cements, however, tended to destroy the available porosity into which tissue could grow.

According to the present invention, an osseous cement for orthopaedic or dental application comprises the mixture of 10 to 40% by weight of organic or inorganic particles which are leachable by body fluids, are of particle size 50 to 250 u (average) and are present in an amount within said range of 10 to 40V,, and in a particle size within the range 50 to 250 microns such that they form a continuous porous structure in the cement obtained from the composition when leached therefrom in situ, 20 to 40 / by weight of an acrylic monomer, 35 to 65U/,, by weight and preferably not more than 60 by weight of an insoluble particulate filler diffusion of which from the cement formed from the mixture is negligible in situ and which is non-toxic, non-carcinogenic, nondegrading, non-swellable in body fluids, chemically stable, biologically inert and desirably is such as to raise the viscosity of the composition to produce a pliable, mouldable paste, and which has a particle size of less than 100cm, and optionally a polymerization initiator for the acrylic monomer, the leachable particles being non-toxic, hard and essentially nondeformable, and not soluble or swellable in the monomer or polymer obtained therefrom, having a melting point above the polymerization temperature of the acrylic monomer, having approximately the same pH as the extra-cellular fluid of the host in situ (as determined by measuring the pH of distilled water left in contact with the said particles) and having substantially no effect on the ionic strength of the body fluids of the host when in situ.

As will be explained below, the incorporation of an adequate amount of particulate leachable materials will provide a cement with a sufficient porosity through which the fibrous tissue can grow to strengthen the implant-to-tissue bond. The mere incorporation of a soluble chemical into acrylate polymers such as polymethylmethacrylate to provide porosity has been proposed in U.S. Patent 2,347,567.

In that preference, however, the monomer and a germicide in crystalline form are charged into a mould in which polymerization is effected to form a surgical implant. The implant is formed in the shape of a screw which is screwed into the bone.

In turn, the body fluid dissolves the crystalline germicide so that a porous structure is obtained into which osseous bridges can be formed. This is unlike the present invention which is concerned with the formation of a cement which is used to fix the implant, and not to the implant per se. In the present invention leachable particles are incorporated into the monomer or partially polymerized resin to form a cement which is polymerized in the body-not in a mould. The particles then function not only to provide a porous bond interface, but, as will be explained below, also to prevent thermal necrosis of surrounding bone tissue, and to prevent outmigration of the monomer. Moreover, the product of this earlier patent has germicidal crystals which would burn the surrounding tissues, and hence would be detrimental for implant purposes. That is, germicidal crystals would be toxic to the surrounding tissue, and hence unsuitable. Moreover.

some of the germicide will invariably remain in the mixture after the germicide has become leached out, which would prevent growth of tissue into the pores of the cement. One object of the present invention, as described in detail below, is to provide for tissue growth into the osseous cement, and thereby improve the longevity of the bond.

U.S. Patent 3,215,137 discloses the use of sucrose esters as a liquid diluent to prevent excessive heat generation during polymerization of methylmethacrylate, which is used for immobilizing bandages for fractured limbs; however, leachable particles are not used, and the use contemplated is outside the body and not internal.

None of these references suggests a method of simultaneously providing a cement which permits the ingrowth of tissue so as to provide a high strength porous bond, elimination of monomer toxicity, and elimination of thermal necrosis.

Thus. broadly, according to this invention, leachable organic or inorganic particles are admixed with a polymerizable acrylic monomer and optionally a polymerization initiator and possibly an accelerator.

The purpose of including leachable particles in the cement is to provide a method of rendering the cement bond sufficiently porous that fibrous tissue can grow through the cement layer and thereby ultimately provide a stronger bond either between the bone parts or between a bond part and an implant used to secure the bone parts. After the cement has hardened, the leachable particles contained therein can be leached leaving a porous bond interface. Moreover, the large surface area of the leachable particles absorb quantities of liquid monomer which can therefore no longer escape from the implantation site to the central circulation.

Since the leachable particles are in proximity to the bulk of the polymerizing acrylic monomer, the monomer absorbed to the particles polymerizes with the remaining monomer and is prevented from leaving the bond site. However, the particles continue to be leachable so that the final bond structure is porous. It would have been surmised that the coating of the polymerized monomer onto the surface of the particles would prevent the body fluids from leaching the leachable particles but this does not occur.

The presence of the particles provides a further effect in that they act as a heat sink for the exothermic heat generated by the polymerization reaction. The heat generated therefore is expended in raising the relatively high heat capacity particles and, therefore, no significant thermal necrosis occurs to the surrounding bond tissue. Moreover, the presence of the particles dilutes the quantity of monomer required so that less exothermic heat is generated.

Another unexpected result of this invention is the discovery that, although it was expected that the presence of the pores in the bond interface would weaken the bond strength until the fibrous tissue could grow through the interface, in fact, the bond was almost as strong as if the pores were not induced. The result is therefore that cement with a continuous pore system is formed which allows tissue ingrowth which further strengthens the bond and improves longevity.

The result of the introduction of the leachable particles into the acrylic cement is therefore that thermal necrosis is substantially eliminated, the introduction of toxic quantities of monomer into the circulatory system is severely curtailed, and a bond is formed which is characterized by a high strength and a high degree of porosity.

which permits the growth of fibrous tissue through the interface.

The leachable particles used for the purposes of this invention may be of any chemical composition. organic or inorganic. but the following criteria should be considered when selecting particles for a particular use.

1. The particles should be soluble in the extracellular fluid which surrounds the bonding site so that they may be leached from the cement to provide a porous interface.

2. The particles should have essentially the same pH as the extracellular fluid se that no shift in pH of the fluid is induced.

3. The particles should have substantially no effect on the ionic strength of the extracellular fluid.

4. The particles should be non-toxic.

which also implies non-carcinogenic and non-antigenic.

5. The particles should be hard and essentially non-deformable as otherwise they may not be sufficient to maintain the proper size porosity.

6. The particles should be in the form of particles of 50 to 250 u (average) and preferably 100 to 200 p. Much larger particle sizes will tend to require undesirably large quantities of leachable particles to assure continuous porosity and will also discourage tissue ingrowth, whereas smaller average diameters will tend to hinger the growth of fibrous tissue through the bond interface.

7. The particles should not melt below or near the curing temperature of the cement, since otherwise they would lose their shape during the cement application.

8. The particles should not swell in or imbibe monomer or body fluids when heated to curing temperature, since swelling or dissolution could fracture the implant or could crack the cement.

Particles which meet these criteria include particles of non-ionic compounds, such as monosaccharides such as glucose, fructose, xylose, mannose, fucose and galactose: the disaccharides, such as sucrose, lactose and maltose; the higher soluble mers, such as oligosaccharides; the metabolites, such as amino acids; or salts or esters of inorganic or organic acids, including the buffer salts and hydrated forms. such as calcium glycerate, sodium fumarate, calcium isovalerate, calcium citrate, calcium succinate, calcium fumarate, CaCO3.MgCO3, calcium laurate.

calcium glycerophosphate, calcium lactate.

calcium saccharate, calcium salicylate.

calcium carbonate, tricalcium phsophate, hydroxyapatite, and calcium gluconate.

The particular chemical composition of the particles is not critical so long as they meet the above criteria.

Suitable acrylic monomers which mav be used in forming the cement include acrylic acid. methylacrylate, methyl methacrylate, ethyl acrylate. ethyl methacrylate, propyl acrylate, butyl acrylate, propyl methacrylate and higher alkyl acrylate and methacrylate homologues; methylethyl- and propyl - a - haloacrylates and higher alkyl homologues thereof wherein halo includes chloro, bromo, fluoro, and iodo: hydroxymethyl-methacrylate; halomethyl methacrylate, haloethyl methacrylate and halopropyl methacrylate; hydroxymethyl methacrylate, hydroxyethyl methacrylate, and hydroxypropyl methacrylate: hydroxymethyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate and the like; and halomethyl acrylate, haloethyl acrylate, halopropyl acrylate, as well as mixtures and copolymerizable mixtures of 'the above acrylic monomers and other monomers when such mixtures are used the total weight of the mixture of monomers must be in the range 2040 '. Suitable cements can be formed from copolymers of any of the above monomers with styrene and derivatives thereof such as a- methylstyrene, vinyl acetate, vinyl halides, vinylidene halides, alkyl vinyl ethers and ethylene derivatives.

The quantity of leachable particles used in this composition is 10 to 40can by weight, and preferably 25 to 35 X; by weight based on the weight of the total composition.

The quantity of particles and the size of the particles are selected such that at least a substantial proportion of the particles touch in the cement.

After leaching, therefore, the resulting polymer product will have a continuous porous structure. In this manner, a significant proportion of the pores will extend from one side of the cement to the other (i.e. they will be continuous).

The minimum size of the particles is such that the growth of fibrous tissue is not hindered by the size of the resulting pores.

The maximum size of the leachable particles is such that the strength of the bond and continuity of the pores are not adverselv affected, or the fibrous tissue ingrowth impeded.

The mix preferably should contain a suitable polymerization initiator For this purpose, any free radical initiator as is commonly used for acrylic polymerization reactions is usable including organic per oxides, such as benzoylperoxide, t-butyl peroxide, hydroperoxides, persulphates, perborates, permanganates, azonitriles and organic hydroperoxides such as t-butyl hydroperoxide.

In order to assist in initiating the polymerization reaction and to control it.

accelerators are most desirable. Suitable acceleraters include organic bases such as dimethyl - p - toluidine and pyridine.

If a spontaneously decomposing peroxide such as t-butylhydroperoxide is used, a reducing agent accelerator should be used such as ferrous ion.

If cationic initiation of the polymerization reaction is used, a lewis acid such as boron trifluoride should be used for the polymerization of, for example, 2methylstyrene, and alkyl vinyl ethers.

If the polymerization reaction is initiated by anionic polymerization catalysts, strong bases such as sodium amide and organometallic bases should be used.

Other initiating sources for the polymerization reaction include condensation polymerization catalysts as well as heat, ultraviolet radiation and high energy irradiation such as X-rays.

In order to use the composition for orthopaedic or dental application it is necessary to add a filler to raise the viscosity of the composition to a pliable, mouldable paste. For this purpose, it is preferable to use an acrylic polymer, which may be formed from the same or different monomer as is used in the mix. The selection of acrylic polymers is preferred because it will readily cross-link with the polymer being formed and therefore will contribute to the strength and homogeneity of the product. When such polymers are used they should be of sufficiently high molecular weight to render polymer diffusion from the cement formed from the mixture negligible in situ. The filler polymers of course must be bob-toxic. noncarcinogenic, non-degrading and nonswelling in body fluids. The fillers must also be chemically stable, biologically inert and have mechanical qualities appropriate for restorative bone cements. Suitable polymer materials which may be used as fillers include the following, such as polymethylmethacrylate, methylmethacrylate- styrene copolymers, polyethylmethacrylate and polymers of the appropriate monomers listed among the previously mentioned monomers as well as their stereospecific polymers and copolymers thereof.

The filler is used in an amount sufficient to form a dispersion or organosol of solid polymer in monomer liquid and to bring the mix to a pliable mouldable paste and is preferably soft and smooth like a putty. For this purpose the filler is used in an amount of 35 to 65"" by weight of total composition and also has a particle size of less than 100,,t.

preferably less than 2,u.

It has been found that the particle size and surface area of the filler is quite important for obtaining the proper consistency. The desired consistency may also be obtained by partial polymerization of the monomer, i.e. by stopping the polymerization reaction at an intermediate stage to form a high molecular weight, pliable material containing residual monomeric material which can subsequently be polymerized.

The mix is then applied to the bone parts or to a bone and a metal bone implant, or to a fractured tooth or bone and is polmerized in situ. Since the leachable particles act as a heat sink, exothermic heat generated by the reaction is taken up and a very careful control of the optimum temperature is possible. The presence of the particles and the filler also functions to reduce the quantity of monomer being polymerized by a dilution effect, which of course also has a favourable effect in keeping the exothermal heat generated low.

Following the polymerization, the crystals will dissolve in the extracellular fluid and leave behind pores in the acrylic cement bond. After the bond is formed the leachable particles will be leached out over a probable period of several weeks. The actual time period during which the leaching occurs is clinically insignificant.

As discussed above, one of the important aspects of this invention is the discovery that as a result of the replacement of some of the cement bulk by leachable particles, the amount of monomer used in each procedure is proportionally reduced. This reduction is also reflected in the amount of monomer escaping to the central circulation. Moreover, due to the small sizes of the leachable particles, the total surface area of the leachable particles is large. This surface area will absorb monomer molecules prior to their polymerization, thus contributing to the over-all reduction of monomers escaping from the bond site. As the absorbing layer is probably not more than one or two monomer molecules thick, the particles remain perfectly leachable.

The presence of continuous pores would be expected to result in a significant loss in strength. but this is not so if the particles are used in the above quantity range. The extent of the strength loss, in fact, does not weaken the cement beyond clinical tolerance. Moreover, what strength loss does occur is expected to be regained as the fibrous tissue grows into the pores and through the bond interface.

Having now generally described the invention a further understanding can be attained bv reference to certain specific examples.

EXAMPLES IA. IB. IC and ID Reduction in Polymerization Temperature and Thermal Necrosis Sucrose crystals having particle sizes of 50 to 250 microns (average) nere admixed with Simplex P, (Registered Trade Mark) a commerciallv available acrylic cement composed of 66 " w/w powdered polymethylmethacrylate 330 w/w methylmethacrylate-styrene copolymer, about 059n v/v benzoylperoxide (initiator), about 2.6" v/v N.N - dimethyl - p - toluidine (accelerator) and 97.40,, v/v methylmethacrylate and 75 ppm hydroquinone in 20 ml liquid. In the first instance, the quantity of crystals was held constant, so that the variation in crystal to Simplex ratio was attributable to the variation in cement. It was found that the polymerization temperature fell as a function of increasing percent of sucrose crystals as shown in Figure 1. Example IA used 200. by weight sucrose, IB used 300 by weight sucrose, IC used 40", by weight sucrose and ID (comparison example) used no sucrose. The total amount of powdered polymethylmethacrylate and methylmethacrylate-styrene copolymer, the insoluble filler, on the one hand and the amounts of methylmethacrylate monomer on the other hand were within the ranges 35 to 65?") by weight and 20 to 400 by weight of the composition respectively.

EXAMPLE 2 Reduction of Monomer Migration Into the General Circulatory System Experimental 1. 9.1 grams of Simplex P was extrudedsix minutes after mixing the components- through a inch nozzle into 30 ml of outdated human blood and kept there for fourteen more minutes. The blood was then poured off, beaker and sample rinsed with distilled water (which was added to the blood) and shaken in a separatory funnel with 30 ml of cyclohexane. This mixture was then transferred to high density polyethylene tubes and centrifuged at about 1000 R.P.M. for seven minutes. There were, after that, three layers. On top (a) clear cyclohexane, in the middle (b) a cyclohexane rich plasma layer and at the bottom (c) packed red blood cells.

First, layer (a) was pipetted off. The layers (b) and (c) wre shaken again with another 30 ml of cyclohexane and centrifuged. Again layer (a) was removed and added to the first layer (a). Then the gellike plasma layer (b) was removed and centrifuged with cyclohexane used to wash the funnel. etc. The clean cyclohexane layer on top was pipetted off and added to the previously collected cyclohexane layers The rest was discarded.

'. The experimental steps of experiment (1) were repeated exactly, but this time using 120. 120/140 mesh sugar in the cement.

U.V. Absorption at 215 m Solution (I) was first diluted to a total of 100 ml. Then a small sample of this was diluted 50 times and measured against pure cvclohexane as reference. Read 39.0 units.

Solution (2) was also made up to 100 ml.

A small sample of this diluted 50 times.

Read 24.3 units with pure cyclohexane as reference.

The above results show that the presence of sucrose crystals caused a significant reduction in monomer migration.

EXAMPLE 3 The procedure of Example 2 was repeated except using tricalcium phosphate (TCP) instead of sucrose crystals. The U.V.

absorption at 215 u was as follows: Weight of Sample, U.V.

grams %TCP Absorbance 5.0 0 72.0 7.1 0 91.4 11.3 0 137.0 4.7 12.5 75.0 6.9 12.5 87.2 12.1 12.5 137.7 3.6 37.5 42.2 7.2 37.5 68.0 10.5 37.5 81.1 These results show that the extent of monomer migration is inversely proportional to the weight of TCP present.

EXAMPLE 4 In Vivo Experiments A dog about 30 pounds was prepared according to conventional test procedures for cement implantation. 20.8 g of Simplex P (cement) was prepared without the addition of crystals and a portion of the cement was inserted into a 1/3 inch diameter hole into the ilium near acetabulum and worked through, mushrooming at the other side.

Implantation was completed within 67 minutes. 5 ml of blood samples were taken from the femoral vein before the junction with the femoral vein of the other leg at 7 minutes and 7t minutes, and every minute thereafter until a total sample of 50 ml was obtained.

This experiment was repeated using the same cement except with the addition of 45 ,, weight TCP. 21.3 g of the mixture was worked as above.

Blood samples were taken as above. The blood samples were extracted and subjected to U.V. analysis. The U.V. absorbance was as follows: U.V.

absorbance Control 14.4 No TCP 84.3 45(,)-, TCP 27.6 A dog weighing 27 pounds was subjected to the above treatment using 28.08 grams of plain cement, and 30.25 g of cement containg 25% weight sucrose. The U.V.

readout was as follows: Control 17.2 No sucrose 75.3 25% sucrose 45.6 The addition of sucrose and TCP effected significant reduction in the quantity of monomer released.

EXAMPLE 5 Ingrowth of Fibrous and Bony Tissues The ingrowth of fibrous and bony tissues by mixing various sucrose crystal percentages and sizes with the Simplex, was investigated prior to polymerization.

Following implantation and hardening the sucrose will dissolve and leave behind a continuous pore system.

Plugs were implanted on fifty-two rabbit ilia. Three types of plugs were embedded: 1) those in which the sucrose crystals had been thoroughly mixed with the solid component, 2) those in which the plugs were rolled in sucrose crystals as soon as the dough became malleable, and 3) those with sucrose crystals mixed in as well as applied superficially.

As a control, plain acrylic cement (Simplex) was used in two ilia. Sucrose concentrations of 10, 20, 30, 40, 50 and 60 percent were used in the mixed samples.

Three grades of sucrose crystal sizes were used, 53-63 jt, 105-125 , and 250297 y.

The rabbits were sacrificed at periods ranging from one day to nine months. A series of control rabbits were sacrificed at one to four days. The tissue ingrowth seen in the stained sections was rated on an arbitrarily chosen 1+ to 4+ scale.

No tissue growth was noted in the plugs from the control rabbits which had plain Simplex and in those plugs which were removed at one to four days. No or little (1+) tissue ingrowth was noted in the plugs with 10 und 20 percent sucrose. Much (3+ to 4+ fibrous and osseous in nature, fairly cellular, and well stained with Van Gieson stain. The tissue occurred in the lamellar arrangement characteristic of collagenous tissue. The tissue within the plugs also contained a large amount of hydroxyproline, an amino acid which appears only in collagen.

As expected, tissue ingrowth did not penetrate deeply into the plugs that were only superfically coated with sucrose crystals.

EXAMPLE 6 Effect of Porosity and Pore Size on the Strength of the Acrylic Resin The diametral tensile strength (DTS) was tested using an Instron (Registered Trade Mark) tensile testing machine. DTS measurements provide a convenient method for evaluation of tensile strengths of acrylic implants. The DTS can be directly calculated from the load at collapse and the dimensions of the cylindrical plugs. The results have indicated that unmodified Simplex resin is two to three times stronger than bone and about 15% stronger than roots of teeth. Consequently, a considerable percentage of porosity can be tolerated without impairing the strength factors beyond tolerance. Moreover, the strength will be increased as the tissue ingrowth occurs. These results show that the effect of pore size is small compared to that of percentage porosity. The results are shown in Figure 2.

The porous cement of the invention can be used in the treatment of fractures and bone defects. A number of preliminary experiments have been carried out to investigate the the usefulness of such applications. Sections from the tibia of rabbits have been segmentally resected for this purpose. Steinman pins, coated with acrylic dough containing sucrose crystals, were inserted into proximal and distal segments of the tibia. X-ray evidence shows that healing is satisfactory.

One of the greatest problems in the treatment of amputees has been the failure to develop devices which could be implanted into the amputee's limbs rather than using external fixation. The reason for failure in the development of such an implantable proisthesis has been the rejection at the skin-implant interface.

It is thought possible that a porous acrylic cement in accordance with this invention could find application in the fixation of tooth implants and artifical limbs in which epithelial cell growth occurs around tooth implants and artificial limbs.

WHAT WE CLAIM IS: 1. An osseous cement composition for orthopaedic or dental application which comprises the mixture of 10 to 40% by weight of organic or inorganic particles which are leachable by body fluids, are of particle size 50 to 250 L (average) and are present in an amount within said range of 10 to 40 " and in a particle size within the range 50 to 250 microns such that they form a continuous porous structure in the cement obtained from the composition when leached therefrom in situ, 20 to 40 by weight of an acrylic monomer, 35 to 65 ó by weight of an insoluble particulate filler diffusion of which from the cement formed frm the mixture is neglible in situ and which is non-toxic, non-carcinogenic, nondegrading, non-swellable in body fluid, chemically stable, biologically inert and which has a particle size of less than 100 ,u, and optionally a polymerisation initiator for the acrylic monomer, the leachable particles bieng non-toxic, hard and essentially non-deformable, and not soluble or swellable in the monomer or polymer obtained therefrom, having a melting point above the polymerization temperature of the acrylic monomer, having approximately the same pH as the extracellular fluid if the host when in situ, (as determined by measuring the pH of distilled water left in contact with the said particles) and having substantially no effect on the ionic strength of the body fluids of the host when in situ.

2. An osseous cement as claimed in Claim I in which the insoluble particulate filler is present in an amount not greater than 60 by weight.

3. An osseous cement as claimed in Claim I or Claim 2 in which the particular filler is an acrylic polymer.

4. An osseous cement as claimed in Claim I or Claim 2 in which the particulate filler is an acrylic polymer of sufficiently high molecular weight to render diffusion thereof from the cement obtained from the mixture negligible.

5. An osseous cement as claimed in any of the preceding Claims in which the leachable particles are particles of a monosaccharide, a disaccharide, an oligosaccharide, a metabolite, an organic acid salt, an organic acid ester, or an inorganic buffer salt.

6. An osseous cement as claimed in any of Claims 1 to 4 in which the leachable particles are particles of calcium glycerate, sodium fumarate, calcium isovalerate, calcium citrate, calcium succinate, calcium fumarate, CaCO3.MgCO3, calcium laurate, calcium glycerophosphate, calcium lactate, calcium saccharate, calcium salicylate, calcium carbonate,

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (8)

**WARNING** start of CLMS field may overlap end of DESC **. fibrous and osseous in nature, fairly cellular, and well stained with Van Gieson stain. The tissue occurred in the lamellar arrangement characteristic of collagenous tissue. The tissue within the plugs also contained a large amount of hydroxyproline, an amino acid which appears only in collagen. As expected, tissue ingrowth did not penetrate deeply into the plugs that were only superfically coated with sucrose crystals. EXAMPLE 6 Effect of Porosity and Pore Size on the Strength of the Acrylic Resin The diametral tensile strength (DTS) was tested using an Instron (Registered Trade Mark) tensile testing machine. DTS measurements provide a convenient method for evaluation of tensile strengths of acrylic implants. The DTS can be directly calculated from the load at collapse and the dimensions of the cylindrical plugs. The results have indicated that unmodified Simplex resin is two to three times stronger than bone and about 15% stronger than roots of teeth. Consequently, a considerable percentage of porosity can be tolerated without impairing the strength factors beyond tolerance. Moreover, the strength will be increased as the tissue ingrowth occurs. These results show that the effect of pore size is small compared to that of percentage porosity. The results are shown in Figure 2. The porous cement of the invention can be used in the treatment of fractures and bone defects. A number of preliminary experiments have been carried out to investigate the the usefulness of such applications. Sections from the tibia of rabbits have been segmentally resected for this purpose. Steinman pins, coated with acrylic dough containing sucrose crystals, were inserted into proximal and distal segments of the tibia. X-ray evidence shows that healing is satisfactory. One of the greatest problems in the treatment of amputees has been the failure to develop devices which could be implanted into the amputee's limbs rather than using external fixation. The reason for failure in the development of such an implantable proisthesis has been the rejection at the skin-implant interface. It is thought possible that a porous acrylic cement in accordance with this invention could find application in the fixation of tooth implants and artifical limbs in which epithelial cell growth occurs around tooth implants and artificial limbs. WHAT WE CLAIM IS:

1. An osseous cement composition for orthopaedic or dental application which comprises the mixture of 10 to 40% by weight of organic or inorganic particles which are leachable by body fluids, are of particle size 50 to 250 L (average) and are present in an amount within said range of 10 to 40 " and in a particle size within the range 50 to 250 microns such that they form a continuous porous structure in the cement obtained from the composition when leached therefrom in situ, 20 to 40 by weight of an acrylic monomer, 35 to 65 ó by weight of an insoluble particulate filler diffusion of which from the cement formed frm the mixture is neglible in situ and which is non-toxic, non-carcinogenic, nondegrading, non-swellable in body fluid, chemically stable, biologically inert and which has a particle size of less than 100 ,u, and optionally a polymerisation initiator for the acrylic monomer, the leachable particles bieng non-toxic, hard and essentially non-deformable, and not soluble or swellable in the monomer or polymer obtained therefrom, having a melting point above the polymerization temperature of the acrylic monomer, having approximately the same pH as the extracellular fluid if the host when in situ, (as determined by measuring the pH of distilled water left in contact with the said particles) and having substantially no effect on the ionic strength of the body fluids of the host when in situ.

2. An osseous cement as claimed in Claim I in which the insoluble particulate filler is present in an amount not greater than 60 by weight.

3. An osseous cement as claimed in Claim I or Claim 2 in which the particular filler is an acrylic polymer.

4. An osseous cement as claimed in Claim I or Claim 2 in which the particulate filler is an acrylic polymer of sufficiently high molecular weight to render diffusion thereof from the cement obtained from the mixture negligible.

5. An osseous cement as claimed in any of the preceding Claims in which the leachable particles are particles of a monosaccharide, a disaccharide, an oligosaccharide, a metabolite, an organic acid salt, an organic acid ester, or an inorganic buffer salt.

6. An osseous cement as claimed in any of Claims 1 to 4 in which the leachable particles are particles of calcium glycerate, sodium fumarate, calcium isovalerate, calcium citrate, calcium succinate, calcium fumarate, CaCO3.MgCO3, calcium laurate, calcium glycerophosphate, calcium lactate, calcium saccharate, calcium salicylate, calcium carbonate,

tricalcium phosphate, hydroxyapatite or calcium gluconate.

7. An osseous cement as claimed in any of Claims I to 4 in which the leachable particles are sucrose crystals.

8. An osseous cement as claimed in any of Claims I to 4 in which the leachable particles are particles of tricalcium phosphate.