Osteoconductive coating of implants made of plastic

Abstract

The invention relates to biomaterials based on plastics, such as polyaryl polyether ketone (PEK), and to methods for producing and using same. The following describes how a mechanically stable coating made of a porous bone substitute material, e.g. Nano Bone®, is applied to polyaryl polyether ketone (PEK), e.g. polyether ether ketone (PEEK), as a result of which the problem of poor cell adhesion on plastics surfaces of this kind can be solved. The bone substitute material can be applied both dry as a powder and also in a wet spraying method. The coating is a result of briefly melting the polymer surface and the resulting partial penetration of the previously applied layer. In the process, the molten polymer penetrates into nanopores of the bone substitute material and thus establishes a firm connection.

Claims

1. A method for the manufacture of a plastic implant characterized in that a highly porous bone substitute material is embedded in a surface layer of the plastic implant in the areas in which the bone is to grow onto the implant, wherein the bone substitute material protrudes from the surface, said method being characterized in that: a mold for the manufacture of the implant is coated with an aqueous slurry of a highly porous bone substitute material in the areas in which the implant is to have contact with the bone; the layer is dried; and subsequently a plasticized plastic is introduced into the mold.

2. The method for the manufacture of a plastic implant according to claim 1, characterized in that the surface of the plastic is caused to melt.

3. The method for the manufacture of a plastic implant according to claim 1, characterized in that the slurry consists of water and granulate of crystalline hydroxyapatite (HA), embedded in an amorphous porous matrix of silicon dioxide.

4. The method for the manufacture of a plastic implant according to claim 3, wherein the size of the granules is in the range of 1 to 50 μm.

5. A method for the manufacture of a plastic implant characterized in that a highly porous bone substitute material is embedded in a surface layer of the plastic implant in the areas in which the bone is to grow onto the implant, wherein the bone substitute material protrudes from the surface, said method being characterized in that: the areas of the implant onto which the bone is to grow are hydrophilized; a layer of silicon dioxide sol in which crystalline hydroxyapatite is dispersed is applied to the hydrophilized areas of the implant, wherein the solid matter concentration (HA and SiO2) of the sol is in the range of 0.2 to 10% by weight, and the ratio of HA to SiO2 is in the range of 90 to 10% by weight to 40 to 60% by weight, then the resulting sol layer is dried, and subsequently the plastic implant surface is heated to an extent that the plastic penetrates into nanopores of the dried sol layer formed.

6. The method for the manufacture of a plastic implant according to claim 5, characterized in that the silicon dioxide sol is manufactured with the dispersed hydroxyapatite by using sodium hydrogen phosphate and calcium chloride for precipitation of HA, wherein the concentration of sodium and chlorine ions is decreased, the water content is reduced to less than 1% of the total solvent, and a silica sol, which is mixed with the hydroxyapatite suspension, is generated by the hydrolysis of tetraethyl orthosilicate (TEOS).

7. The method for the manufacture of a plastic implant according to claim 5, characterized in that the layer of silicon dioxide and HA is activated by an oxygen plasma before or after heating of the plastic implant surface.

8. The method for the manufacture of a plastic implant according to claim 6, wherein the ion concentration is decreased to less than 0.1% of the initial concentration.

9. The method for the manufacture of a plastic implant according to claim 6, wherein an organic acid as catalyst is used for the hydrolysis of TEOS.

10. The method for the manufacture of a plastic implant according to claim 9, wherein the organic acid is acetic acid.

Description

LEGEND

(1) FIG. 1 shows a layer of the bone replacement material manufactured according to example 1 which is partially sunken in PEEK. Scale: 20 μm.

(2) FIG. 2 shows a scanning electron microscopic image of a coated PEEK mold after 6 weeks in vivo. The scanning electron microscopic image allows the confirmation of the element-specific composite by means of EDX (energy dispersive X-ray spectroscopy) measurements. Scale: 200 μm.

(3) FIG. 3 shows the same specimen as FIG. 2 in the form of an incident light image of the histological thin section. The incident light image clearly shows the change in the structure of the polymer after the coating procedure and the bone tissue that is anchored to the coating. Scale: 200 μm.

(4) FIG. 4 shows two PEEK-Cages each which were dipped with their lower tip into water that was stained black. On the left side (A) no wetting occurred as the implant has a hydrophobic surface. On the right side (B) wetting occurs strongly after the implant has obtained a hydrophilic surface due to treatment with plasma.

(5) FIG. 5 is a representation of a layer coated according to example 3 by dual spraying by means of a scanning electronic image, on the right of which PEEK and in the middle of which the molten bone substitute material coating can be seen which is about 5 μm thick (Scale 6 μm).

(6) FIG. 6 shows a scanning electron microscopic image of a section of an implant according to the invention (A, scale 2 μm) and an analysis of elements along the horizontal line shown in FIG. 6A (Linescan)(B). The area labeled by vertical lines (positions A and B) is identical in FIG. 6A and FIG. 6B and shows the area of the coated layer. FIG. 6 B shows from top to bottom the shares of carbon, silicium and calcium. It can be seen that the layer has a gradient. The layer is penetrated by the PEEK (carbon) to a higher extend in the lower sections (left in FIGS. 6 A and B) as in the upper sections (right in FIGS. 6 A and B).

(7) FIG. 7 shows a layer of the bone substitute material manufactured according to example 1 that is partially sunken into PEEK. Scale 35 μm.

(8) FIG. 8 shows a typical light microscopic image of a histological specimen from the in vivo experiment of example 2 from the control group after 2 weeks. The problem of bad cellular adhesion can be seen from the connective tissue layers between bone tissue and the PEEK implant surface (arrows).

(9) FIG. 9 shows readings of the bone-implant-contact from the in vivo experiment by means of the coating according to the invention in example 2. After 2 weeks resting time an improvement of about 15% of the bone-implant-contact was measured due to the coating, after 4 weeks an improvement of about 10% and after 6 weeks about 15%. The readings were measured with the semi-automatic Axio Vision 4.8 (Zeiss) software.

EXAMPLE 1

(10) Use of a NanoBone® S39-Powder Coating on Rotationally Symmetric PEEK Molds

(11) NanoBone® S39-granulate (Artoss GmbH, Rostock, Germany, bone substitute material manufactured according to EP 1624904 B1) is ground to a fine powder (particle size 5-100 μm). The PEEK body to be coated is placed in a cylindrical recess (parallel arrangement of the rotational axes of the PEEK body and the recess) that intended especially for this body in a stainless steel mold. The free space between the body to be coated and the metal mold is filled with ground granulate and compressed by means of a little pressure (e.g. about 0.1 to about 5 MPa) in the direction of the rotational axis of the PEEK body. The stainless steel mold (with PEEK body and ground granulate) is then inserted into an induction coil (TIG 30/100, HUTTINGER Elektronik GmbH). Heat can be introduced into the PEEK body very quickly due to the induction process (e.g. 380° C. to 400° C., measured at the surface of the form, for 5 seconds), which only leads to melting of the PEEK surface. The molten PEEK adapts to the nanoporous surface of the NanoBone® and establishes a strong connection. FIGS. 1 and 7 show the sunken layer of biomaterial in the PEEK.

EXAMPLE 2

(12) The molds coated according to example 1, were tested in an in vivo experiment with white New Zealand rabbits with 2, 4 and 6 weeks resting time each with 6 implants in the control group (pure PEEK surface) and 6 implants in the coating group. The implants were inserted laterally in the distal thigh bone. Corresponding experiments often serve the purpose of testing tooth implants in the state of the art. After euthanasia, the implants are processed by means of the thin section technique and stained with toluidine blue, to be able to carry out a histological and histomorphometrical analysis.

(13) The newly nanostructured surface of the PEEK prevents penetration of bone degradating cells, simply due to the new magnitude of the structure in the surface. Also the macroscopic roughness, which is caused by the coating procedure can play a role.

(14) As a consequence, no cell-PEEK interface but only a cellNanoBone® interface exists, wherein the NanoBone® is firmly bound to the PEEK. FIG. 2 shows a scanning electron microscopic image of a coated PEEK mold after 6 weeks in vivo. The scanning electron microscopic image allows confirmation of the element-specific composite by means of EDX measurements. FIG. 3 shows the same specimen as FIG. 2 as an incident light microscopic image of the histological thin section. The incident light microscopic image clearly shows the change in polymer structure due to the coating procedure and the bone tissue anchored to the coating.

(15) FIG. 8 shows a typical incident light microscopic image of a histological specimen from the control group after 2 weeks. The problem of the bad cell adhesion can be seen from the connective tissue layers between the bone tissue and the PEEK-implant-surface (arrows).

(16) The in vivo experiment additionally shows an increase in the bone-implant-contact by about 10-15% (see FIG. 9, measured with the semi-automatic Axio Vision 4.8 (Zeiss) software).

EXAMPLE 3

(17) A silicon dioxide sol is manufactured with the dispersed hydroxyapatite by use of sodium hydrogen phosphate and calcium chloride for the precipitation of HA, by lowering the concentration of the sodium and chlorine ions by means of rinsing and filtering, wherein the ion concentration is reduced to about 0.1% of the initial concentration, by reducing the water content by means of adding and filtering of ethanol, wherein the water content is about 1% of the total solvent. By means of a hydrolysis of tetraethyl ortho silicate (TEOS) using acetic acid as catalyst a silica sol is generated. Ethanol, the sol and the HA suspension are then mixed in such shares that a solid matter content (SiO.sub.2 and HA) of 1% and a mass ratio of HA to SiO.sub.2 of 76 to 24 develops.

(18) A PEEK implant as used in spinal surgery (cage) is treated in low pressure oxygen plasma for 60 seconds to generate a wetted surface. In FIG. 4 two PEEK cages each were dipped into water stained black with the lower tip. No wetting occurs on the left side because the implant has a hydrophobic surface. On the right strong wetting occurs after the implant has received a hydrophilic surface by means of a plasma treatment.

(19) Afterwards, the PEEK implant is sprayed with the manufactured sol for one second while rotating and dried in the air stream. This is repeated multiple time, e.g. twice or three times, in case this is desired for the layer thickness.

(20) Subsequently, the rotating implant is entered into an air stream having 350°, thus, causing the surface to pass over into the fluid state and “sinking” of the layer. Depiction of the coated layer in FIG. 5 by means of a scanning electron microscopic image. An elemental analysis along the horizontal line (Linescan) was carried out in FIG. 6. The area labeled by vertical lines (position A and B) is identical in the left figure and the diagram on the right and shows the area of the coated layer. The diagram on the right side shows the shares of carbon, silicon and calcium from top to bottom. It can be seen that the layer has a gradient. The layer is penetrated by the PEEK (carbon) to a higher extend in the lower sections (left in the diagram) than in the upper sections (right in the diagram).

(21) Removal of organic remains from the surface of the layer occurs by means of a finalizing oxygen plasma treatment.