WO1997038741A1

WO1997038741A1 - Process for producing a biodegradable bone replacement and implant material, as well as biodegradable bone replacement and implant material

Info

Publication number: WO1997038741A1
Application number: PCT/DE1997/000736
Authority: WO
Inventors: Dieter Reif; Barbara Leuner; Olaf GÜNTER
Original assignee: Biovision Gmbh Entwicklung, Herstellung Und Vertrieb Von Biomaterialien In Ilmenau
Priority date: 1996-04-12
Filing date: 1997-04-11
Publication date: 1997-10-23
Also published as: AU2692197A; DE19614421A1; DE19614421C2

Abstract

A process is disclosed for producing a biodegradable bone replacement and implant material, as well as a material based on a composite material which consists of a pH-neutral salt mixture of alkaline and alkaline earth salts, and/or of alkaline earth salts of one or several polybasic inorganic acids, such as phosphoric acid, carbonic acid, silicic acid and sulphuric acid as biodegradable inorganic component and a representative from the group of the in vivo degradable biopolymers as biodegradable organic component. The quantitative proportion of the composite components varies in a range from 5 to 99 % by mass for the biodegradable organic component and 1 to 95 % by mass for the biodegradable inorganic component. Formed bodies made of the biodegradable bone replacement and implant material are produced by injection moulding, extrusion, sintering and hot-pressing. The geometric shape and dimensions of the formed bodies may be modified by a machining or non-cutting thermal forming process.

Description

Process for the production of a biodegradable bone substitute and implant material and a biodegradable bone substitute and implant material

The invention relates to a method for producing a biodegradable bone replacement and implant material and a biodegradable bone replacement and implant material which can be used for the temporary filling of bone defects and as a starting material for the production of moldings for biodegradable implants

Numerous different treatment methods have been proven for the healing of bone defects and for the fixation of bone fractures. In the past 10 to 15 years, however, it can be observed both for defect filling and for osteosynthesis that synthetic biodegradable materials are increasingly being used for certain indication areas Materials preclude foreign bodies from remaining in the organism from the outset or save the patient the burden of a second operation

Nail, plates and screws made from biodegradable polymers are increasingly being used especially for the treatment of little or no stressed bone fractures using the osteosynthesis method. Different polymer groups have already been proposed for this application of particular importance. Their composition and manufacture is described in EP 0 401 844, among others

Biomechanically, these Polymeπmplan.ate bring advantages in that they initially take over the supporting function of the bone fragments, however, these are gradually transferred to the bones in the course of the healing process in connection with their biodegradation. This reduces the risk of inactivity atrophy of the bone.

The disadvantage of using these materials, however, remains that they have no bioactivity and favor the growth of connective tissue rather than that of bone tissue. In addition, high concentrations of acidic degradation products are released in the implant store during the degradation phase, especially in the case of massive parts and materials with a short degradation time, which can lead to tissue reactions and / or signs of osteolysis in the vicinity of the implant store.

Various mixtures of biodegradable polymers and bio-ceramics have already been proposed to improve the bioactivity, the growth of the implant with the bone tissue or to promote the growth of bone tissue into porous shaped implants.

For example, biodegradable and partially biodegradable composites are described in DE 41 20 325. The materials have an open-pore structure and are characterized by proportions of calcium phosphate ceramic over 50% by mass. The ceramic particles are coated with a maximum of 50% of their surface with a biopolymer to enable the bone to grow in well. At the same time, the biopolymer forms the cement substance for the calcium phosphate ceramic. Various bone ceramics are preferred as inorganic composite components and as biopolymers, among others. Polylactide and polyglycolide are proposed. The composite components are heated by means of microwave radiation and sintered or, after softening, deformed by mechanical pressure.

Another biodegradable composite material is claimed for protection in DE 27 42 128. The material consists of synthetic, biological compatible and biodegradable polymer with a modulus of elasticity similar to that of bone and an inorganic filler that is able to stimulate the absorption of the polymer in favor of new bone tissue. The inorganic filler consists of calcium phosphate, especially TCP, and is contained in an amount of 0.5 to 30% by mass.

DE 26 20 891 describes composites based on biodegradable calcium phosphates and biodegradable polymers. Tricalcium phosphate is preferably used as calcium phosphate, and polylactides and polyglycolides are proposed as polymers. The composites are produced by mixing the shredded individual components and hot pressing.

EP 0 192 068 protects composites of 25 to 75% by mass of unsintered calcium phosphate ceramic, preferably hydroxylapatite, tricalcium phosphate, calcium pyrophosphate and 25 to 75% by mass biodegradable polymer. The polymer components include Lactic and glycolic acid polyesters are used. Up to 30% by mass of water-soluble, pore-forming materials can be included as further additives. The composite components are mixed and then polymerized.

Composites of biodegradable or non-biodegradable calcium phosphate ceramics, preferably tricalcium phosphate or hydroxylapatite and polymers of lactic and glycolic acid are described in WO 90/01342. The polymer component contains molecular weight-regulating coreactants in order to set molar masses in the range from 200 to 10,000 g / mol. This makes the composites kneadable to solid at body temperature. The ceramic portion is in the range of 20 to 65% by mass as granules and / or powder.

The composites described in WO 88/06873 contain polyester of fumaric acid and a polyhydroxy alcohol as polymer components. As Calcium phosphate ceramics are suggested tricalcium phosphate or hydroxyapatite. In addition to the calcium phosphate ceramic, the composites contain other biodegradable calcium salts, such as calcium sulfate, calcium carbonate and calcium sulfate hemihydrate.

All of the composite materials described are intended for use in medical technology as implant and / or bone replacement materials or for anchoring orthopedic implants in the bone tissue. Different processes are described for the production of the materials, all of which have in common that they do not subject the composite components to high thermal loads. It is also typical that the spectrum of the calcium phosphate ceramics used is limited to the known calcium orthophosphates and hydroxyapatite. The absorption rate of the inorganic constituents is thereby limited to a narrow range, or the inorganic component is not absorbed at all and remains as a foreign body in the organism. Likewise, methods of high shaping accuracy for the production of implants, such as injection molding, are not provided for the materials described in the prior art, so that a deficit with regard to shape and dimensionally accurate composite implants must be deduced.

A general problem in the production of biodegradable composites using calcium orthophosphates and biomaterials derived therefrom is that they are subject to a more or less strong hydrolysis in the presence of water or moisture. As a result of this hydrolysis reaction, these biomaterials act like strong bases. This behavior limits their use as a composite component, especially when interacting with chemically sensitive biopolymers. In certain combinations, there may even be considerable chemical incompatibility of the composite constituents, which may result in the production and processing of the desired composite by thermal mixing and molding. make the rendering process impossible.

Specifically, the production of dimensionally and form-fitting moldings using thermal processes, e.g. Injection molding or hot pressing using thermally sensitive polymers, such as polyester of lactic and glycolic acid and their copolymers, can thus be prevented. For calcium phosphate ceramics with increased absorption rate, e.g. In WO 91/07357, due to the particularly strong basic reaction, the polymer chains are degraded so rapidly that composites cannot be produced by means of thermal processes via the polymer melt.

If it is possible to produce composite moldings by means of injection molding, it is often found that the mechanical properties of the samples are limited and that the strength values of the pure polymer cannot be achieved with unreinforced composites. It can be assumed that this disadvantage is due to the already beginning degradation of the polymer chains and an insufficient interface strength between the inorganic and organic components. One of the causes of insufficient interfacial strength is partial polymer degradation, preferably at the ceramic grain / polymer matrix interface, which leads to the formation of weak points and thus reduces the mechanical properties of the composites.

The object of the invention is to create a method and a material of the type mentioned at the outset in order to expand the field of composition for biodegradable bone substitute and implant materials and the possibilities for producing shaped bodies, and to improve the mechanical strengths of biodegradable bone substitute and implant materials . O 97/38741 PC17DE97 / 00736

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According to the invention, the object is achieved with a method in which the basicity of the biodegradable inorganic constituent in at least one layer of its surface is adjusted to a pH value in the neutral range of 7 ± 1, mixed intimately with the biodegradable organic constituent, and then is transferred into the composite. Advantageous embodiments of this method are specified in subclaims 2 to 7.

The biodegradable bone substitute and implant material according to the invention consists of a composite based on a biodegradable organic polymer and a biodegradable inorganic component. The biodegradable organic constituent is a representative of the in vivo degradable polymers, while the biodegradable inorganic constituent consists of particles of a slightly to sparingly soluble, synthetic, stoichiometric and / or non-stoichiometric composition, amorphous, amorphous crystalline and / or crystalline alkali Alkaline earth and / or alkaline earth salt mixture of one or more polybasic inorganic acids. The particles of the salt mixture have at least one surface layer such a chemical composition that their freshly saturated aqueous solution has a pH in the range of 7 ± 1.

The biodegradable organic polymer is preferably a polyester from the group of polyglycolides, polylactides or their copolymers. The biodegradable organic polymer preferably consists of poly (L-lactide), poly (D-lactide), poly (D.L-lactide), poly (glycolide) or copolymers derived therefrom, the comonomer fraction being up to 50% by mass.

Comonomers in the form of copolymerizable cyclic esters include, in addition to the various lactide forms, glycolide, dioxanone, trimethyl lencarbonate or a lactone of ß-hydroxybutyric acid and / or ß-hydroxyvaleric acid in question. In order to ensure sufficient mechanical strength for load-bearing applications, the biodegradable organic polymer in the finished and sterilized composite molded body has at least a molecular weight of 100,000 g / mol. Furthermore, a special form of the biodegradable organic polymer is designed as a polymer blend and represents a mixture of mechanically reinforcing, different high molecular weight polymers.

Depending on the proportion of the biodegradable organic component and the composite production process, this functions as a matrix of the composite or cementes the particles of the biodegradable inorganic component. For sufficient mechanical strength of the biodegradable bone replacement and implant material, it is desirable that the particles of the inorganic constituent are surrounded as completely as possible by the organic constituent and that a high interfacial strength is achieved.

The biodegradable inorganic component of the composite consists of particles of an alkali-alkaline-earth and / or alkaline-earth salt mixture of orthophosphoric acid, sulfuric acid, silica and / or carbonic acid. Na ₂ O and / or K ₂ 0 are preferably present as alkali oxides and CaO and / or MgO are preferably contained as alkaline earth oxides. The particles of this salt mixture have a pH in the range of 7 ± 1 in their freshly saturated aqueous solution. This value does not change by more than ± 0.2 in a period of 30 minutes after the first measurement immediately after the saturated solution has been prepared.

The particles of the biodegradable inorganic component consist of an unsintered precipitate, a sintered and / or a melt product. Their size varies with the desired goal in

Range from 1 to 500 μm. The biodegradable bone replacement and im- Plantate material contains the biodegradable organic component in an amount of 5 to 99 mass% and the biodegradable inorganic bed component in an amount of 1 to 95 mass%.

The specific adjustment of the basicity of the biodegradable inorganic constituent is of particular importance in solving the problem according to the invention. In addition to the favorable physiological effects on cell growth, the targeted adjustment of the pH in the physiological range has, above all, advantageous procedural effects. A biodegradable inorganic composite component which produces a pH of around 7 when suspended in water leads to surprising results ¬ as a much less degradation of the polymer component during thermal shaping than, for example when strongly alkaline alkaline earth metal and / or alkaline earth phosphates are added. With such a "neutral" biodegradable inorganic composite component, the degradation speeds in the range of the working temperatures of thermal shaping processes are reduced to such an extent that the producibility of moldings from the bone substitute and implant materials according to the invention is improved by means of e.g. Injection molding significantly improved, partly even the production is made possible.

The known methods of acid-base reactions for salt formation are used to produce the biodegradable inorganic constituent. The proportions of the components are calculated in such a way that, for example, when precipitating from aqueous solution or sintering suitable compounds or melting them, the salt mixture formed as a reaction product has a neutral character and the pH value of its freshly saturated aqueous solution corresponds to the criteria mentioned above . In the simplest case, the basicity of the biodegradable inorganic constituent is adjusted by composition of the determined amounts of Components of the salt mixture and their homogeneous mixing, sintering or fusion.

Biodegradable inorganic constituents according to the invention, which are produced via high-temperature reactions, are generally referred to as ceramics, glasses or glass ceramics. However, their manufacturing process, which is based on solid-state diffusion or melting reactions, can also be viewed as an acid-base reaction or salt reaction. The resulting reaction products are therefore classified as sparingly or sparingly soluble salts or salt mixtures, the chemical composition of which does not have to comply with the stoichiometric laws of defined chemical compounds. Such materials include described in WO 91/07357.

If the basic and acidic components of the biodegradable inorganic component are in the desired ratio, the saiz mixture reacts

"neutral" and has a pH value in the range of the physiological value in its freshly saturated aqueous solution. Predominate e.g. the basic proportions, the freshly saturated aqueous solution has pH values which are in the strongly alkaline range. PH values up to 1 1 are quite possible.

Salts or salt mixtures with such high pH values are unsuitable as a biodegradable inorganic component. According to the invention, their use is possible in that the particles of the biodegradable inorganic component are subjected to at least superficial leaching or acid conversion before being combined with the biodegradable organic component. In this reaction, the basic components of the material are neutralized and partially leached out. The surface reaction layer also serves as a diffusion barrier and prevents further passage of the basic components from the particle core. The thickness of the reaction layer is chosen at least so that the im The neutral pH of a freshly saturated aqueous solution does not change by more than ± 0.2 within 30 minutes. This is generally sufficient to ensure processability with the polymer component.

At the same time, it was surprisingly found that a particle surface treated in this way with a neutral reaction layer which ensures a pH in the physiological range, compared to untreated biodegradable inorganic constituents, ensures significantly higher mechanical strengths in the composite.

Shaped bodies of the biodegradable bone substitute and implant material have an open-pore structure, depending on the manufacturing process, or are free of open and / or closed porosity. In order to achieve an open-pore structure, the mixture of the composite components contains up to 60% pore-forming agents. This addition and the selected sintering conditions make it possible to set an open porosity in the range from 10 to 50%. Shaped bodies, which are manufactured by the hot-pressing process or injection molding technology, on the other hand, are free of any kind of porosity, provided that one works with vacuum-dried starting materials.

Shaped bodies of the biodegradable bone substitute and implant material are produced after the dry mixing of the finely comminuted, vacuum-dried organic and inorganic composite components by one of the thermal processes sintering, hot pressing, extruding or injection molding. The manufacturing process can also consist of combinations of these processes. For example, it is also possible to use the extrusion of the composite components for their intimate mixing. Favorable grain fractions of the composite components for the mixing process are <500 μm, advantageously <200 μm. If the biodegradable inorganic component predominates in the mixture of the composite components, the mixture is preferably produced from solutions and / or suspensions by evaporating the solvent and / or by precipitation of the dissolved components. For this purpose, the polymer portion is dissolved in a suitable solvent, for example acetone or chloroform, the ceramic portion is homogeneously suspended and the polymer is precipitated by adding a suitable liquid, such as alcohol or water. During the precipitation the polymer encloses the suspended component and the composite components co-precipitate.

A complete coating of the entire ceramic grain by the polymer is obtained when the solvent is evaporated from a suspension of the biodegradable inorganic component in a solution of the biodegradable organic component. For the formation of the composite, this complete covering has advantages with regard to the interfacial strength between the biodegradable inorganic and organic constituents, and improves the mechanical properties of the composite. At the same time, it permits lower working temperatures during thermal shaping, which in turn reduces polymer degradation. Such a polymer-encased biodegradable inorganic constituent can also be processed further by the process of dry mixing the composite components. Of course, it is also possible to encase the particles of the biodegradable inorganic component by the biodegradable organic component by combining the components in a fluidized bed.

Finally, porous moldings of the biodegradable inorganic constituent according to the invention are obtained by soaking open-pored moldings of the biodegradable inorganic constituent with solutions of the biodegradable organic constituent and evaporating the solvent. This procedure leads to a high ceramic content Structural consolidation of the molded body of the biodegradable bone replacement and implant material.

When using the biodegradable inorganic component in particle form, the shaped bodies of the biodegradable bone substitute and implant material obtain their final shape directly through the thermal shaping process, or their final shape is produced from a preform by thermal shaping. If the biodegradable inorganic constituent is used as an open-pore sintered shaped body, the pre- or final shape is predetermined by it. In all cases, the shaped body made from the biodegradable bone substitute and implant material according to the invention can still be machined in its geometric shape and the final dimensions by cutting shape change.

The invention is explained below using exemplary embodiments.

Example 1:

Calcium carbonate in aqueous suspension and orthophosphoric acid are reacted in a molar ratio of 3: 2. A salt mixture of calcium hydrogen phosphate and calcium carbonate is formed as the reaction product. The freshly saturated aqueous slurry shows a pH of 7.2. This value does not change over a period of 30 minutes. The precipitation product is vacuum-dried and made available in a grain fraction <100 μm as a biodegradable inorganic component (baB) baB1 for further investigations.

BaB1 is mixed intensively with a crushed and vacuum-dried poly (L-lactide-co-D, L-lactide) 70:30 in a particle size <250 μm as a biodegradable organic component (boB). The proportions of baB1 are 5, 10, 20 and 30% by mass. The mixtures are injection molded into test specimens measuring 40 × 5 × 2 mm ³ and tested for their flexural strength. The moldings are well shaped, of homogeneous structure, dense and free of porosity. The bending strength values are summarized in the table below.

Exemplary embodiment 2:

BaB1, as prepared in Example 1, is intimately mixed with a comminuted and vacuum-dried poly (D, L-lactide-co-glycolide) 85:15 as boB. The particle size of the boB is <500 μm. The amount of baB1 is 20% by mass.

The dry mixture is extruded as a strand, chopped <1 mm and pressed into cylinders and foils in heated molds. The moldings have a homogeneous distribution of the components in the composite, are dense and non-porous.

Embodiment 3: Phase-pure sintered α-tri-calcium phosphate (TCP) is reacted with dilute orthophosphoric acid, which is adjusted to a pH of 2.0, in aqueous suspension for one hour. The reaction product is washed, vacuum-dried and made available in a particle size <100 μm as baB2 for further investigations. A freshly saturated aqueous solution of baB2 has a pH of 7.4. This value practically does not change within an hour.

45% by mass of baB2 are intimately dry-mixed with 55% by mass vacuum-dried poly (D, L-lactide-co-glycolide) in a particle size of 250 to 500 μm as boB and cold-pressed into cylindrical compacts. The compacts are sintered at 160 ° C for one hour. The composite sintered bodies have an open porosity of 30%. Their compressive strength is 14 N / mm ² . Some of the composite sintered bodies are converted as preforms by hot pressing into dense, largely pore-free shaped bodies and another part is changed in their geometric shape by turning, drilling and milling. Example 4:

50% by mass of a mixture as described in Example 3 are mixed homogeneously with 50% by mass of ammonium carbonate as pore-forming agent in a particle size of 250 to 500 μm without crushing the particles of the ammonium carbonate. The mixture is cold pressed and the compact is sintered at 160 ° C for one hour. The sintered body has an open porosity of 55% and can be machined very well.

Example 5:

To produce various other baB on the melting state, three glass ceramics GK3, GK4 and GK5 (see table) are melted and the cooled melt flow <200 μm is reduced.

Legend: pH, pH of the freshly saturated aqueous solution at 37 ° C; pH ₃₀ , pH of the saturated aqueous solution after standing for 30 minutes at 37 ° C. The comminuted materials are suspended in an orthophosphoric acid diluted to pH = 2.0 for 1 hour, filtered off, washed with water and vacuum-dried. They are provided as baB3, baB4 and baB5 (see table) for further investigations.

Example 6:

45% by mass baB4 are intimately mixed with 55% by mass poly (L-lactide-co-D, L-lactide) 70:30 as boB, formed into cylindrical pellets which are sintered at 150 ° C for 1.5 hours. The cylindrical moldings have an open porosity of 40% and are very easy to machine. Their compressive strength is 12.6 N / mm ² .

Example 7:

45 mass% baB5 and 55 mass% crushed and vacuum-dried poly (DL-lactide-co-glycolide) 50:50 are mixed intimately, cold formed into cylindrical compacts and sintered at 150 ° C. for 1.5 hours. The composite sintered bodies have an open porosity of 40%. Their compressive strength is 16.9 N / mm ² .

Example 8:

A mixture composed as in Example 7, but the particles of baB5 are coated with a polymer layer before mixing. For this purpose, they are soaked in a solution of boB in chloroform and dried. The composite sintered bodies, as produced according to Example 7, have an open porosity of 40%. Their compressive strength is significantly increased and is 18.0 N / mm ² .

Example 9:

To study the influence of surface neutralization on the mechanical properties of the composites, cylindrical composites are Sintered bodies with baB3 to baB5 compared with composite sintered bodies using the untreated glass ceramics GK3 to GK5 according to WO 91/07357. The production of the composite sintered body corresponds to Examples 6 and 7. The results are summarized in the table.

A significant increase in compressive strength by a factor of 2 to 3 is observed with the "neutralized" glass ceramics.

Embodiment 10: A porous sintered molded body is produced from phase-pure α-TCP. This has an open porosity of 50%. The sintered shaped body is treated with dilute orthophosphoric acid, adjusted to a pH of 2.0, treated for 1 hour, washed and vacuum-dried. The sintered molding thus treated has a pH of 7.2 in its freshly saturated aqueous solution. This value does not change within an hour. The sintered shaped body is available in this form as baB6 for composite formation.

The sintered shaped body baB6 is soaked with a solution of poly (L-lactide-co-D, L-lactide) 70:30 in chloroform, the solvent evaporates, the Soak repeatedly, the solvent evaporates again and then the body is vacuum dried. The composite body has a compressive strength of 8.5 N / mm ² compared to the untreated ceramic sintered molded body (5.5 N / mm ² ). It absorbed 6.0% by mass of the boB.

Example 11:

In calcium carbonate, an equimolar amount of 20% is replaced by magnesium carbonate. This mixture is reacted in a molar ratio of 3: 2 with orthophosphoric acid in which 10% equimolar is replaced by sulfuric acid. The resulting salt mixture is washed, vacuum-dried and crushed to a grain size <100 μm. In this form it is available as baB6 for further investigations.

60 mass% baB6 are homogeneously suspended in a solution of 40 mass% poly (D, L-lactide-co-glycolide) 50:50 as boB in acetone and kept in suspension. BaB6 and the boB are precipitated from this suspension together by injecting a water-alcohol mixture and vacuum-dried. The dry mixture is pressed into dense moldings in a heated mold. These are easy to machine.

Claims

Claims:

1. A method for producing a biodegradable bone replacement and implant material, consisting of a composite based on a biodegradable organic and a biodegradable inorganic constituent, characterized in that the biodegradable inorganic constituent is basic in at least one layer of its surface pH value in the neutral range of 7

± 1 set, intimately mixed with the biodegradable organic component, and then transferred to the composite.

2. The method according to claim 1, characterized in that the basicity of the biodegradable inorganic constituent is adjusted by an acid-base reaction in aqueous suspension.

3. The method according to claim 1, characterized in that the adjustment of the basicity of the biodegradable anoragnic component is carried out by the composition of the salt mixture.

4. The method according to any one of the preceding claims, characterized ge indicates that the mixture of biodegradable inorganic and organic constituent is additionally added a pore-forming agent up to 60% by mass.

5. The method according to any one of claims 1 to 4, characterized gekennzeich¬ net that the intimate mixing of the composite components from their solutions and / or suspensions by evaporation of the solvent and / or by precipitation.

6. The method according to any one of the preceding claims, characterized ge indicates that the transfer into the composite is carried out according to one of the thermal methods sintering, hot pressing, extruding or Spritz¬ casting and / or corresponding combinations of these methods.

7. The method according to any one of the preceding claims, characterized ge indicates that the transfer into the composite takes place in that the particles of the biodegradable inorganic component are coated with the biodegradable organic component and then sintered.

8. Biodegradable bone substitute and implant material, consisting of a composite based on a biodegradable organic and a biodegradable inorganic component, characterized in that the biodegradable organic component from a representative of the in vivo degradable biopolymers, the biodegradable inorganic component from particles of a synthetic , stoichiometrically and / or non-stoichiometrically composed amorphous, amorphous-crystalline and / or crystalline alkali-alkaline earth metal and / or

Alkaline earth salt mixture of one or more polybasic inorganic acids and the particles of the salt mixture have at least one layer of their surface such a chemical composition that their freshly saturated aqueous solution has a pH in the range 7 ± 1.

9. Biodegradable bone replacement and implant material according to claim 8, characterized in that the biodegradable organic constituent of poly (L-lactide), poly (D-lactide) or copolymers derived therefrom with comonomers in the form of copolymerizable cyclic esters consists.

10. Biodegradable bone substitute and implant material according to claim 8 or 9, characterized in that the comonomers of D, L-lactide, meso-lactide, glycolide, dioxanone, trimethylene carbonate or a lactone of ß-hydroxybutyric acid and / or ß-hydroxyvale - Rian acid exist and the comonomer fraction is up to 50% by mass.

11. Biodegradable bone substitute and implant material according to one of claims 8 to 10, characterized in that the biodegradable organic component is a polymer blend of different high molecular weight, mechanically reinforcing, biodegradable polymers.

12. Biodegradable bone replacement and implant material according to one of claims 8 to 11, characterized in that the pH of the freshly saturated aqueous solution of the biodegradable inorganic component within 30 minutes after the first measurement by no more than ± 0, 2 changed.

13. Biodegradable bone replacement and implant material according to one of claims 8 to 12, characterized in that the biodegradable inorganic component consists of particles of a precipitation product, an unsintered, sintered and / or melt product and an average grain size in the range from 1 to 500 μm.

14. Biodegradable bone substitute and implant material according to one of claims 8 to 1 3, characterized in that the mixture of the composite components 5 to 99% by mass of the biodegradable organic polymer and 1 to 95% by mass of the biodegradable contains inorganic component.

15. Biodegradable bone replacement and implant material according to one of claims 8 to 14, characterized in that the mixture of the composite components contains up to 60% by mass of pore-forming agents.

16. Biodegradable bone replacement and implant material according to one of claims 8 to 15, characterized in that it has an open porosity of 10 to 50%.

17. Biodegradable bone replacement and implant material according to one of claims 8 to 15, characterized in that it is free of open porosity.