EP0888096A1

EP0888096A1 - Process for producing a bone substitute material

Info

Publication number: EP0888096A1
Application number: EP97907038A
Authority: EP
Inventors: Axel Kirsch; Dietmar Hutmacher
Original assignee: Individual
Current assignee: Individual
Priority date: 1996-03-19
Filing date: 1997-01-31
Publication date: 1999-01-07
Also published as: DE19610715C1; WO1997034546A1; AU1923797A

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

Process for making a bone substitute

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

In the case of biomechanically stressed bone defects, it does not make sense to introduce the bone substitute material as granules, since there is no bone regeneration due to the mechanical stress. For such indications, highly porous block bodies into which the bone can grow are preferred. Ceramic bone substitute materials are, however, very brittle, so that blocks made from these materials cannot absorb larger mechanical loads.

It is the object of the invention to provide methods for producing a bone substitute material with which a highly biocompatible bone substitute material is given improved mechanical strength and resilience.

This object is achieved with a method according to claim 1 or claim 2. Advantageous refinements are the subject of the dependent claims.

According to the invention it is provided according to a first aspect that several channels are introduced into the ceramic block, the channels are filled with bioabsorbable polymer granules and then the ceramic block with the polymer granules is heated to a temperature above the melting or flow temperature of the polymer granules. The polymer granulate melts in the channels and, when it cools down to room temperature, anchors itself in the form of a supporting structure in the pores of the ceramic block adjacent to the bores, thus ensuring the desired mechanical strength without the majority of the pores in the ceramic being removed from it bioresorbable polymer would be closed. This ensures that when such a polymer-reinforced ceramic block is inserted into the bone, the contact surface with the bone mainly consists of a pure ceramic surface. This is essential for good biocompatibility of the bone replacement material.

The temperature to which the ceramic block with the polymer granules is to be heated depends on the selected bioabsorbable polymer. As materials, plastics from the group of polyesters come into question, and from these in particular the Poly (α-hydroxyl acids). A temperature range of 180 ° C to 230 ° C is appropriate for this.

As an alternative to heating the plastic block with the polymer granulate in a heating cabinet, the fumigation process has proven to be advantageous. This is a process for shaping thermoplastic materials, in which the thermoplastic material is introduced into a mold cavity in free-flowing form or in the form of a preform, and the viscosity of the plastic is reduced with the aid of supercritical substances to such an extent that the plastic becomes flowable and / or can be deformed. The gassing is carried out with one or more gases, possibly also liquefied gases, under high pressure, and they should preferably be in the supercritical state. It can be adjusted in terms of process technology that the polymer takes on a compact or foamed structure within the bores and the adjacent pores. Fumigation at the comparatively low temperatures and under high pressure presupposes that the gas has good solubility in the respective polymer. The solubility of gases or liquids in polymers is a function of pressure and temperature. It is known that particularly good solubility parameters are achieved when the gas changes to the supercritical state. Supercritical gases or liquids are known. These include carbon dioxide, ethylene, propane, nitrogen and water. Depending on the supercritical substance used in each case, the gassing process can be carried out at a pressure in a range from 50 to 800 bar (5 × 10 ⁶ Pa to 8 × 10 ⁷ Pa).

Carbon dioxide is advantageously used for the bone substitute material mentioned, which is preferred for the invention. The suitable pressure range is between 50 to 200 bar (5 x IO ⁶ pa to 2 x 10 ⁷ Pa;. It is often expedient to use biologically active agents such as growth factors, antibiotics, pain-relieving agents, agents which influence cell division and vascularization, coagulating or anti-coagulating agents, immunosuppressive or immunostimulating agents, cytokines, chemical attractiveness, enzymes and combinations of which to be introduced into the bone substitute material. The effectiveness and, above all, the mechanisms of action of the said agents are known to the person skilled in the art. For example, growth factors can serve to stimulate cells in general and, if appropriate, special cell populations to intensify growth in order to fill up the existing tissue or bone defect as quickly as possible. The use of antibiotics is particularly indicated if there are tissue defects that are large or difficult to clean or if the environment in which the bone substitute material is introduced has a high bacterial load. Agents that influence cell division and vascularization also allow rapid regeneration of the tissue or bone defect. Depending on the blood circulation conditions, the addition of coagulating or, if necessary, anti-coagulating agents can be beneficial. The use of immunosuppressive agents is particularly indicated if, for example, the healing process would otherwise deteriorate as a result of allergic reactions. Conversely, immunostimulating agents can be advantageous if it is desired to generate an enhanced immune response in the area of the bone replacement material. As a result of their mechanism of action, the immigration of various cell populations means that cytokines and chemical acctance can represent a way of largely controlling the healing process. The addition of enzymes allows a further modification of the regeneration process and can affect the regenerated or regenerating tissue. The gassing process is advantageously carried out at a temperature which is below 37 ° C. Therefore, the addition of thermolabile, biologically active agents is possible without any problems.

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

It is further advantageous, also in the sense of an inexpensive manufacturing process, if the channels are formed running parallel to one another.

However, for stabilization it can also be expedient to form groups of channels which run obliquely or even perpendicularly to one another in order to optimally absorb mechanical loads which act on the ceramic block from different directions.

The channels can be closed on at least one side. In particular for horizontally running channels, it is also conceivable to leave one side closed and to close the opposite side after filling with polymer granules with ceramic plugs.

Suitable materials for the highly porous ceramic block are synthetic ceramics, glasses and glass ceramics, or ceramics of natural origin. Synthetic ceramics are, for example, hydroxylapatite, α-tricalcium phosphate and β-tricalcium phosphate. The ceramics of natural origin are made from cattle bones Algae (Algipore ^) and corals. A typical chemical formula for a bioactive glass ceramic is Ca0-P2θ5-SiC> 2 •

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

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

Figure 1 schematically with a highly porous ceramic block

Shows channels;

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

Figure 3 shows the finished ceramic block;

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

Figure 5 shows another example of the arrangement of the

Channels illustrated in a ceramic block according to the invention.

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 * ^R) . The channels 20 are parallel to one another and arranged in rows, only one such row being indicated schematically in FIG. 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 granulate 30 melts in the channels 20, as illustrated in FIG. 3, and forms the desired mechanical structure 40 in the ceramic block 10 after cooling to room temperature. It has been found that a composite bone replacement molded article produced by the method according to the invention exhibits a 100% to 200% higher mechanical strength than the untreated, highly porous ceramic block.

Example 2

A ceramic block prepared as in Example 1 is filled with free-flowing polymer granules made of poly (α-hydroxyl acids). In a pressure chamber, this filled ceramic block is gassed at room temperature in a carbon dioxide atmosphere at 50 to 200 bar. The carbon dioxide dissolves in the polymer and with it 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 may 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 Figure 5, a first row of channels 20 can 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.

The features of the invention disclosed in the above description, in the drawing and in the claims can be essential for realizing the invention both individually and in any combination.

Claims

Patgntlaimμςhe

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

a plurality of 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

the channels (20, 22, 24) are filled with bioresorbable polymer material (30), either in a pourable form or in the form of a preform; and

then the ceramic block (10) with the polymer material (30) is treated with a substance or a mixture of substances at a temperature T and under high pressure p, at which the substance / the mixture of substances is supercritical, so that the thermoplastic plastic becomes flowable and / or malleable.

3. The method according to claim 2, characterized in that the substance or the mixture of substances consists of carbon dioxide, ethylene, propane, water and / or nitrogen.

4. The method according to claim 2 or 3, characterized gekennzeich¬ net that the pressure p is between about 5 x 10 ⁶ Pa and about 8 x 10 ⁷ Pa.

5. The method according to claim 4, characterized in that the pressure p is between about 5 x IO ⁶ Pa and 2 x IO ⁷ Pa.

6. The method according to any one of claims 2 to 5, characterized in that the temperature T is less than about 37 ° C.

7. The method according to any one of the preceding claims, characterized in that at least one biologically active agent is added to the polymer material and / or the substance / the substance mixture.

8. The method according to claim 1 or 2, characterized gekennzeich¬ net 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 gekennzeich¬ net that the channels (20, 22) are formed running parallel to each other.

10. The method according to claim l or 2, characterized gekennzeich¬ net that the channels (20, 22, 24) are divided into at least two groups, wherein within such a group the channels run parallel to each other and wherein the channels

(24) at least one of the groups runs obliquely to channels (20, 22) of a further 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.