DE19610715C1 - Manufacture of bone replacement material - Google Patents

Abstract

The invention relates to a process for producing a bone substitute material from a high-porous ceramic block (10), which process is characterised in that a plurality of channels (20, 22, 24) are introduced into the ceramic block (10) and are filled with bio-resorbent polymer granules (30). The ceramic block (10) is subsequently heated to a temperature above the melting or flow temperature of the polymer granules (30). The invention also relates to a process for producing bone substitute material from a high-porous ceramic block (10), which process is characterised in that a plurality of channels (20, 22, 24) are introduced into the ceramic block (10) and are filled with bio-resorbent polymer material (30) which is either pourable or in the form of a preform. The ceramic block (10) with the polymer material (30) is subsequently treated with a substance or a substance mixture at high pressure under supercritical conditions, so that the thermoplastic synthetic material is flowable and/or mouldable.

Description

The invention relates to methods for producing a bone replacement material, starting from a highly porous ceramic block.

With biomechanically stressed bone defects it is not it makes sense to incorporate the bone replacement material as granules because there is no bone due to mechanical stress regeneration is coming. For such indications are high porous block bodies preferred, into which the bone grows can.  

Ceramic bone substitute materials are very brittle, however that blocks of these materials have larger mechanical loads can not record.

An implant material is based on DE 41 20 325 A1 a composite material of calcium phosphate ceramic particles and bioresorbable polymer known in which the particles with each other through polymer webs to a three-dimensional of fenporigen structure are connected.

DE 38 26 915 A1 relates to a bone composite material, the body-compatible ceramic work as an essential component substances mixed with body-absorbable oligomers and / or Contains polymers of lower hydrocarboxylic acids, the Resin components from free carboxyl group used pen are practically exempt. Are solid oligomers and / or Polymers of the type mentioned in certain weight ratios with the particulate, finely divided, inorganic bone mixed compound material, the composite is the organi phase as a closed phase, and there is a form available and, if desired, dimensionally stable material supply.

It is the object of the invention to manufacture methods to provide a bone substitute material with a highly biocompatible bone replacement material improved mechanical strength and resilience becomes.

This object is achieved with a method according to claim 1 or claim 2 solved. Advantageous configurations are the subject of the subclaims.

According to the invention it is provided according to a first aspect that several channels are introduced into the ceramic block, which Channels can be filled with bioabsorbable polymer granules and then the ceramic block with the polymer granules a temperature above the melting or flow temperature of the Polymer granules is heated. The polymer granules melt in the channels and anchors itself when it cools down to room temperature door in the sense of a supporting structure in the holes pores of the ceramic block and thus ensures the desired mechanical resilience without the majority of the pores in the ceramic is sealed by the bioresorbable polymer would. This ensures that when you insert a such polymer-reinforced ceramic block in the bones Bone contact surface mainly made of pure ceramic surface exists. This is for good biocompatibility of the bone substitute material is essential.

The temperature at which the ceramic block with the polymer granules to be heated is of the selected bioabsorbable Polymer dependent. Plastics come from the Group of the polyester in question, and from these in particular the  Poly (α-hydroxyl acids). For this there is a temperature range useful from 180 ° C to 230 ° C.

As an alternative to heating the art block with the The polymer granulate in a warming cabinet has been fumigated procedure was found to be advantageous. This is a process ren for the shaping of thermoplastics, in which the thermoplastic in free-flowing form or in Form of a preform is introduced into a mold cavity and the viscosity of the plastic with the help of supercritical Substances are so low that the plastic flows becomes capable and / or can be deformed. Fumigation takes place thereby with one or more gases, if necessary also liquefied gases, under high pressure, being should preferably be in the supercritical state. Here is it technically adjustable that the polymer is a compact or foamed structure within the holes and of the adjacent pores. The fumigation at the ver equally low temperatures and under high pressure assumes that the gas in the respective polymer is good Has solubility. The solubility of gases or liquids in polymers is a function of pressure and Temperature. It is known that particularly good solubility pa parameters can be achieved when the gas is in the supercritical Condition passes. Supercritical gases or liquids are known. These include carbon dioxide, ethylene, propane, Nitrogen and water. Depending on the one turned on The fumigation process can put supercritical substance at a pressure in a range from 50 to 800 bar (5 × 10⁶ Pa up to 8 × 10⁷ Pa).

For the above-mentioned bone preferred for the invention Substitute material is advantageously used carbon dioxide. Of the suitable pressure range is between 50 to 200 bar (5 × 10⁶ Pa up to 2 × 10⁷ Pa).  

It is often useful to use biologically active agents such as Growth factors, antibiotics, pain relievers, Agents that do cell division and vascularization affect, coagulating or anti-coagulating agents, immunosuppressive or immunostimulating agents, cyto kine, chemical attractiveness, enzymes and combinations thereof into the bone replacement material. The effectiveness and above all the mechanisms of action of the said agents are this Known specialist. So z. B. growth factors serve cells in general and possibly special cell po populations to encourage increased growth in order to exi permanent tissue or bone defect as quickly as possible replenish. The use of antibiotics is especially then displayed when it is large area or difficult to cleansing tissue defects or the milieu into which the Bone replacement material is introduced, a high germ load. Agents that cell division and Influence vascularization also allow one rapid regeneration of the tissue or bone defect. In Depending on the blood circulation conditions, the Addition of coagulating or possibly anti coagulating agents. The use of immunosuppressive agents are particularly indicated if, for example, as a result of allergic reactions otherwise worsening the healing process would come. Conversely, immunostimulating agents from Be advantageous if it is desired in the area of the bone to generate an enhanced immune response. Cytokines and chemical attractiveness can result from their Mechanism of action by immigration of different cell populations represent a possibility, the healing process largely control. The addition of enzymes allows one further modification of the regeneration process and can on the regenerated or regenerating tissue impact.  

The gassing process becomes advantageous at one temperature carried out, which is below 37 ° C. Hence the Addition of thermolabile, biologically active Agents easily possible.

It has proven advantageous to use the channels in the Form a ceramic block with a diameter of 2 to 4 mm.

Another advantage, also in the sense of an inexpensive Manufacturing process, it is when the channels are parallel are formed mutually.

However, it can also be useful for stabilization be to form groups of channels that are oblique or even run perpendicular to each other in order to mechani to absorb the stresses arising from different Directions act on the ceramic block.

The channels can be closed on at least one side. It is especially so for horizontal channels conceivable to leave one side closed and the other lying side after filling with polymer granulate Seal ceramic stopper.

The materials for the highly porous ceramic block are syn aesthetically produced ceramics, glasses and glass ceramics or but ceramics of natural origin are suitable. Synthetic Ceramics are, for example, hydroxylapatite, α-tricalcium phosphate and β-tricalcium phosphate. The ceramics natural Are originated from bovine bones (BioOss®), algae (Al gipore®) and corals. A typical chemical The formula for a bioactive glass ceramic is CaO-P₂O₅-SiO₂.

Bioresorbable polymer granules which are used in the present Invention can be used, for example poly (α-hydroxyl acids) already mentioned above, such as poly (L-  Lactide-α-D, L-lactide).

In the following, the invention will be described in more detail by means of examples are explained, reference being made to the drawings will in which

Fig. 1 shows schematically a highly porous ceramic block with channels;

FIG. 2 shows the ceramic block from FIG. 1 with polymer granules filled into the channels,

Figure 3 shows the finished ceramic block;

Fig. 4 shows an example of an arrangement of the channels in a ceramic block according to the invention; and

Figure 5 is a further example of the arrangement of the channels illustrated. In an inventive ceramic block.

example 1

Several channels 20 with a diameter of 2 to 4 mm are drilled in a highly porous ceramic block 10 made of Algipore® or BioOss®. The channels 20 are arranged parallel to one another and in rows, only one such row being indicated schematically in FIG. 1. As can be seen in FIG. 2, polymer granules 30 are filled into these channels 20 . The ceramic block 10 filled with polymer granules 30 is now heated to 200 ° C. in a heating cabinet. As a result, the polymer granules 30 melt in the channels 20 , as illustrated in FIG. 3, and after cooling to room temperature forms the desired mechanical structure 40 in the ceramic block 10 .

It has been found that one according to the invention Process manufactured composite bone replacement molded body 100% to 200% higher mechanical strength compared to shows the untreated, highly porous ceramic block.

Example 2

A ceramic block prepared as in example 1 is included free-flowing polymer granules made of poly (α-hydroxyl acids) filled. This filled ceramic block is in a pressure chamber at room temperature in a carbon dioxide atmosphere at 50 fumigated up to 200 bar. The carbon dioxide dissolves in the polymer and creates a foamed structure within the Holes and the adjacent pores.

It is possible to optimize the mechanical resilience with regard to the acting forces. If, for example, a force acts on two opposite sides of the ceramic body, it can be expedient to arrange the channels 20 , 22 as in FIG. 4, all channels 20 , 22 extending in one direction parallel to one another.

For other loads, it can be expedient to design the channels 20 , 24 in such a way that they pass through the ceramic block 10 in groups in which the channels each run perpendicular to one another. For example, as shown in Fig. 5, a first row of channels 20 may be formed extending in the top-down direction in the drawing, while a second row of channels 24 are spaced apart such that the Channels 24 run perpendicular to the channels 20 .

Reference list

10 ceramic block
20 channel
22 channels parallel to 20
24 channels perpendicular to 20
30 polymer granules
40 polymer structure

Claims (12)

1. A method for producing a bone substitute material , starting from a highly porous ceramic block, characterized in that

• - Several channels ( 20 , 22 , 24 ) are introduced into the ceramic block ( 10 );
• - The channels ( 20 , 22 , 24 ) are filled with bioabsorbable polymer granules ( 30 ); and
• - Then the ceramic block ( 10 ) with the polymer granules ( 30 ) is heated to a temperature above the melting or flow temperature of the polymer granules.

2. A method for producing a bone substitute material, starting from a highly porous ceramic block, characterized in that

• - Several channels ( 20 , 22 , 24 ) are introduced into the ceramic block ( 10 );
• - The channels ( 20 , 22 , 24 ) are filled with bioresorbable polymer material ( 30 ), either free-flowing or in the form of a preform; and
• - Then the ceramic block ( 10 ) with the polymer material ( 30 ) with a substance or a substance mixture at a temperature T and under high pressure p, at which the substance / the substance mixture is supercritical, treated so that the thermoplastic plastic becomes flowable and / or malleable.

3. The method according to claim 2, characterized in that the substance or mixture of substances made of carbon dioxide, Ethylene, propane, water and / or nitrogen. 4. The method according to claim 2 or 3, characterized in net that the pressure p between 5 × 10⁶ Pa and 8 × 10⁷ Pa is. 5. The method according to claim 4, characterized in that the pressure p is between 5 × 10⁶ Pa and 2 × 10⁷ Pa.   6. The method according to any one of claims 2 to 5, characterized characterized in that the temperature T is less than about 37 ° C is. 7. The method according to any one of the preceding claims, characterized in that the polymer material and / or the Substance / the mixture of substances at least one biologically active with agent is added. 8. The method according to claim 1 or 2, characterized in that the channels ( 20 , 22 , 24 ) are formed with a diameter of 2 to 4 mm. 9. The method according to claim 1 or 2, characterized in that the channels ( 20 , 22 ) are formed running parallel to each other. 10. The method according to claim 1 or 2, characterized in that the channels ( 20 , 22 , 24 ) are divided into at least two groups, the channels running parallel to one another within such a group and wherein the channels ( 24 ) at least one of the Groups run diagonally to channels ( 20 , 22 ) of another group. 11. The method according to claim 4, characterized in that the channels ( 24 ) of at least one of the groups run perpendicular to channels ( 20 , 22 ) of a further group. 12. The method according to any one of the preceding claims, characterized in that the channels ( 20 , 22 , 24 ) are closed on at least one side.