CH624572A5 - Bone prosthesis material - Google Patents

Description

The subject of the present invention is a bone prosthesis material, as well as the prosthetic parts produced using this material.

In the present specification, the expression prosthesis parts is used to mean both prosthesis parts in the conventional sense and osteosynthesis parts.

In bone surgery (orthopedic, maxillofacial), the anchoring of rigid implants (joint prostheses, osteosynthesis) is currently carried out either with a cement (methyl methacrylate polymerized in situ), or with metal screws in osteosynthesis,

either by force fitting (centromedullary nail). All these solutions have various drawbacks and, for several years, studies have continued on the use of porous or absorbable materials in vivo to accelerate bone rehabilitation of the bone-implant interface.

The present invention allows the solution of the problem posed by current research aimed at the shaping of osteosynthesis pieces (plates and screws) and the coating of prosthetic implants with substances that are both biodegradable, inducing bone regrowth and having, if necessary for the particular application envisaged, adequate mechanical properties (modulus of elasticity close to that of the bone, sufficient breaking load to avoid rupture in service).

The subject of the present invention is a material for a bone prosthesis, characterized in that it is constituted by a biocompatible and absorbable polymer containing a filler capable of stimulating the resorption of the polymer for the benefit of a newly formed bone tissue.

The material of the invention therefore makes it possible to bring together in the same prosthetic piece the properties of resorbability and activation of the osteogenesis of the contiguous tissue.

The initial mechanical strength of the prosthetic part is determined by the choice of the appropriate polymer and of the filler content, and is possibly improved by the production of composite parts in which the material of the invention is associated with reinforcing elements.

The polymers which can be used for the production of the material of the invention are preferably polymers of high molecular mass (Mp greater than or equal to 150,000 and preferably greater than 200,000). For the implementation of the invention, it is particularly recommended to use poylmers containing the minimum of oligomers. Polymers are therefore used with a low polydispersity index, for example less than 2.

The poylmers which can be used according to the invention can be homopolymers or copolymers.

Among the polymers which can be used in the production of the material according to the invention, the polymers and copolymers of α-hydroxy acids and, more particularly, the homopolymers and copolymers of glycollide and of L-, D- and DL-lactides occupy a predetermined important place. by their excellent biocompatibility and especially by their biodegradability. Their chemical structure and their properties allow these polymers to play a supporting role, to degrade into non-toxic products which can be excreted or metabolized, and to be replaced in the long term by the contiguous tissues specific to the surrounding living organism. .

Among the homopolymers which can be used, mention may be made in particular of homopolymers of glycollide, L-lactide or D-lactide. Among the copolymers which can be used, mention may be made of the products of copolymerization of at least two of these monomers, and in particular the copolymers L-lactide / glycollide, D-lactide / glycollide, DL-lactide / glycollide, and L-lactide / D- lactide (including DL-lactide copolymers).

The filler added to the polymer to produce the material of the invention is a mineral and / or organic filler. The charge can consist of products containing the following ions or some of them: lithium ions, borate, carbonate, fluoride, sodium, magnesium, silicate, potassium and their mixtures. It is possible in particular to use salts based on phosphate anions or anions of the neighboring type and / or salts based on calcium cations or other similar cations or mixtures of these salts. Among the preferred fillers, mention will be made of calcium phosphates and in particular tricalcium phosphate (PO 4) 2 Ca 3.

The filler can comprise, or consist of, any material having a local action stimulating bone regrowth.

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Generally, the charge is present in an amount sufficient to enable it to fulfill the functions indicated above. Generally, the filler is present in an amount of 0.5 to 30% relative to the weight of the polymer. However, in many applications, and in particular when it is desired to produce prosthetic parts having a relatively high mechanical resistance, for example osteosynthesis parts for long bones, materials are preferably used in which the filler is present at a reasonable rate. from 0.5 to 5% relative to the weight of the polymer.

Preferably, the filler is added in the form of a powder, the particles of which have a size which can vary in particular from 1 to 20 (xm.

The presence of a filler in the prosthesis material has original effects:

- The presence of the filler created in the polymer mass of microheterogeneities facilitating the attack at certain points of the material and therefore modifying the resorbability of the latter; there is therefore a physical effect here; the particles of the filler constitute points of preferential attack on the surface, with the constitution of microcavities in which the newly formed bone preferentially develops;

- This new bone formation which is favored takes place to the detriment of the formation of a fibrous capsule which constitutes one of the drawbacks observed with conventional prosthesis parts;

- finally, the load is distributed throughout the mass and not only on the surface, and therefore constitutes a reserve of basic materials for the newly formed bone as resorption progresses.

The following advantages result in particular from these effects:

The preferential attack in certain points of the material leads to a rough surface, which provides a more important interface and explains the intimate bond of the material and the bone observed on the histological sections; this also explains why a stable anchoring of the prosthesis is obtained.

The resorption of the material is not accompanied by a weakening of the bone because, due to the habitation of the points of attack by newly formed bone tissue, the solidity and the mechanical properties are not diminished.

The polymers or copolymers used are compounds prepared by ring-opening polymerization according to the usual methods already described in the literature. However, particular attention must be paid to the purity of the monomers as well as to the polymerization which must be carried out so as to obtain high molecular weights (for example Mp 200000; intrinsic viscosity [t)] CHC13 1.6; polydispersity index I 2) free of oligomers or non-polymerized monomers. It is possible, for example, to purify the crude polymer by washing the monomers and / or oligomers in a solvent.

The incorporation of the filler (also called adjuvant) can be done by conventional methods, that is to say:

- addition of the filler in powder form to solutions of the polymer, followed by precipitation,

- melt mixing,

- mixture of the pulverulent compounds (polymers and filler) followed by hot mixing,

- introduction of the charge into the polymerization medium at the start or during the operations, or

- any other method leading to the formation of a homogeneous mixture of the adjuvant with the polymeric mass.

As described in more detail below, the material of the invention can be used to produce machined or molded parts, or even in the form of granules. The invention therefore relates to said material both in the form of solid blocks and in the form of granules or powder (molding powder).

In the molding powders, the size of the polymer particles is from 1 to 100 μm, and preferably from 10 to 50 μm.

The invention further relates to the application of the material of the invention to the production of bone prostheses made wholly or partially from said material.

Certain particular embodiments of this application, as well as the advantages provided by the material of the invention in certain particular applications, are described below:

a) Manufacture of massive parts intended to be implanted.

These parts are for example screws, plates, centromedullal nails.

res for osteosynthesis and fixation of fractured bones in anatomical position; the subsequent resorption avoids the weakening of the synthesized bones and also avoids a second intervention to remove the material. If the initial mechanical resistance of the osteosynesis assembly is insufficient, to support the efforts of normal mobilization, the treatment can be completed by temporary immobilization using plaster or splints.

Such osteosynthesis parts have in particular the following various advantages: on the one hand, their resorption avoids a second surgical intervention, generally one year after the fracture,

to remove the osteosynthesis pieces; on the other hand, their progressive degradation leads to a gradual transfer of forces from the osteosynthesis part to the bone, which avoids the embrittlement of the bone protected by the osteosynthesis plate, embrittlement generally observed in conventional treatments. not osteosynthesis: in fact, the bone undergoes spongialization when the dynamic loads to which it is normally subjected are in fact supported by the clearly more rigid osteosynthesis plate; finally, the embrittlement of the bone is eliminated during the period of filling of the holes after removal of the intraosseous metal screws.

These pieces can also be pieces for filling up losses of bone substance (following trauma or resection of bone tumors, etc.); one can achieve the final adjustment of the intraoperative parts, for example by grinding or hot modeling if the materials are thermoplastic, as is the case of polylactic, polyglycolic acids and their copolymers.

b) Coating of massive pieces of inert material: for example on the femoral tail of a hip prosthesis, which allows temporary fixation, by force fitting, in the medullary cavity, then promotes definitive fixation by stimulation of regrowth bone in contact with the implant, these prosthesis coatings would replace the cement interface, which constitutes the major source of the loosening observed and, consequently, of the failures of these prostheses.

c) Impregnation of inert porous material: parts or coatings of porous material (ceramic, metal, etc.); resorption of the impregnation material stimulates bone regrowth in the open porosity of the permanent material if the average dimensions of the interconnected pores are of the order of 0.1 to 1 mm.

d) Putting in the form of granules of a few tenths of a millimeter to a few millimeters usable for filling up the losses of bone substance. The bone regrowth will first proceed in the intergranular spaces, then will continue on the grains in the process of resorption. The improvement in the mechanical resistance of the assembly will be accelerated by the stimulation of bone regrowth.

The invention therefore also makes it possible to replace the losses of bone substance by filling them with granules as defined above.

The subject of the invention is therefore in particular the application of the new material to the preparation of bone prosthesis pieces, characterized in that solid pieces are produced, or that massive pieces are made of inert material, or that parts of inert porous material are impregnated using the material for bone implants as defined above.

The transformation into finished objects (osteosynthesis plates, screws, etc.) can be carried out by all the conventional methods of transformation of thermoplastic polymeric materials: injection molding, by compression, block machining, etc., according to the characteristics of the materials. desired which can also be composite materials.

The subject of the invention is also the bone prosthesis parts made wholly or partially from material s

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of the invention, and in particular the solid parts, the coated parts and the impregnated parts described above, as well as the composite parts in which the mechanical properties of the material of the invention are improved with biocompatible reinforcing elements, for example wires Dacron (trade name for a polyethylene terephthalate).

It should be noted that the osteosynthesis plates of the invention allow the use, as a complementary treatment, of the technique of electrical stimulation of osteogenesis, without deformation of the electrical signal.

The following examples illustrate the invention without, however, limiting it.

Example 1:

100 g of high purity L-lactide (recrystallized four times from methyl ethyl ketone) are placed in a polymerization tube. The dry polymerization catalyst (250 mg of Zn powder) is added. The mixture is perfectly degassed by hot-cold and nitrogen-vacuum cycles, then the tube is sealed under vacuum. The whole is placed in a heating chamber and left at 140 ° C for 90 h. The recovered polymer is washed for several hours using dioxane. 90 g of a polymer of high viscosity with all the characteristics of a poly-L-lactide of high molecular weight are obtained (mp == 174 ° C, crystalline at RX, [yj] CHC13 = 1.74 YoungE modulus 360kg / mm2).

Example 2:

20 g of copolymer containing 75% of L-lactic units and 25% of D-lactic units in the form of a very fine powder (grain diameter: 10 to 50 (im) and 1 g of dried calcium phosphate powder are cold mixed so as to obtain a homogeneous powder based on the two constituents.

This powder is placed in a compression mold and molding of a 90 × 15 × 4 mm plate is carried out at a temperature of 100 to 120 ° C. under a pressure of 200 bars, operating so as to avoid the formation of air bubbles.

Example 3:

20 g of glycollide are treated in a similar manner to that described in Example 1, but the quantity of calcium phosphate desired, ie 0.6 g, is added before degassing of the monomer / catalyst mixture. The polymerization is carried out under the same conditions as in Example 1; however, it is necessary to extend the reaction time, which is brought to 8-10 d.

A macroscopically perfectly homogeneous material is obtained which can then be transformed by an appropriate method into prosthetic parts.

5 Example 4:

20 g of the polymer obtained in Example 1 are ground until a fine powder is obtained (particle diameter: 10-50 μm). This powder is mixed with 0.2 g of tricalcium phosphate in the form of a powder (particle diameter: 1-20 (im). A powder which can be used as a molding powder is obtained. This powder can also be processed under action of heat into a syrupy mass which, by extrusion and cutting, provides granules having dimensions of the order of 0.5-1 mm.

15 Example 5:

A 0.5-1 mm layer of the polymer mixture of Example 1, with 1% calcium phosphate, is applied to the femoral tail made of anodized titanium / aluminum / vanadium alloy of a hip prosthesis. 'melted state. The prosthesis piece thus coated is then force fitted into the medullary cavity. In a similar way, the threading of the osteosynthesis screw was coated with the polymer + charge mixture.

Example 6:

The convex part, made of porous sintered hydroxyapatide ceramic, is impregnated under vacuum in a cup (acetabular prosthesis) with a polymer identical to that obtained in Example 3, but to which was added, as filler, not only calcium phosphate, but also sodium fluoride. The impregnation mixture is applied in the molten state.

We have similarly impregnated pieces of joint prosthesis (knees or shoulders) to be inserted into the medullary cavities for anchoring the prostheses.

35 Example 7:

Implanted (without osteotomy) for three months, in sheep, osteosynthesis plates and screws made with the polymer of Example 1 in mixture with 10% calcium phosphate. At the end of the experiment, observation under an optical microscope of the histological sections revealed the absence of detectable fibrous capsule in the interface. There is therefore direct contact between the newly formed bone and the polymer. It should be noted that the osteosynthesis plates and screws were subjected to physiological constraints due to the walking of the animals which were at large.

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Claims (17)

624,572 2 1. Material for the preparation of bone prosthesis, characterized in that it consists of a biocompatible and absorbable polymer containing a filler capable of stimulating the resorption of the polymer for the benefit of a newly formed bone tissue. 2. Material according to claim 1, characterized in that the polymer has a high molecular weight, such that Mp is greater than or equal to 150000. 3. Material according to one of claims 1 or 2, characterized in that Mp is greater than 200,000. 4. Material according to one of the preceding claims, characterized in that the polymer used is a polymer whose polydispersity index is low, for example less than 2. 5. Material according to one of the preceding claims, characterized in that the polymer is a homopolymer or copolymer of α-hydroxy acids. 6. Material according to claim 5, characterized in that the polymer is chosen from the group consisting of homopoly-mothers of glycollide, L-lactide and D-lactide, and the copolymers resulting from the copolymerization of at least two of these monomers, including the DL-lactide copolymer. 7. Material according to one of the preceding claims, characterized in that the filler comprises, or consists of, a material having a local action stimulating bone regrowth. 8. Material according to one of the preceding claims, characterized in that the filler contains salts based on phosphate anions or anions of neighboring type and / or salts based on calcium cations or other similar cations , or mixtures of these salts. 9. Material according to one of the preceding claims, characterized in that the filler consists of calcium phosphate, and in particular by tricalcium phosphate. 10. Material according to one of the preceding claims, characterized in that the filler is present in an amount of 0.5 to 30% relative to the weight of the polymer. 11. Material according to one of the preceding claims, characterized in that the filler is present in an amount of 0.5 to 5% relative to the weight of the polymer. 12. Material according to one of the preceding claims, characterized in that the filler comes from the addition to the polymer of a powder whose particles have dimensions varying from 1 to 20 (im. 13. Material according to one of the preceding claims, characterized in that it is in the form of solid blocks, granules or powders. 14. Use of the material as defined in one of the preceding claims, for the preparation of bone prostheses made wholly or partially from said material. 15. Use according to claim 14, characterized in that bone prosthesis parts are produced, such as solid parts, composite parts, parts made of inert material coated with said material or parts made of inert porous material impregnated with said material. 16. Use according to claim 15, characterized in that the solid parts are produced by molding or by machining of blocks. 17. A bone prosthesis obtained according to claim 14.