Bone substitute and method for producing the same

Abstract

The invention relates to a bone substitute (1) comprising A) a container (2) made of a porous casing (4) which is at least partly provided with openings; and B) a plurality of filler elements (5) which are not connected to one another and which are enclosed in the container (2); wherein C) the filler elements (5) consist of interconnected particles with an average diameter D.sub.p; and D) the openings of the casing (4) are interconnected pores or channels with an average diameter of D.sub.M.

Claims

1. A bone substitute comprising: a container made of a porous casing which is at least partly provided with openings; and a plurality of filler elements which are not connected to one another or to the container and which are fully enclosed within an interior of the container such that the plurality of filler elements cannot escape from the container; wherein individual filler elements are formed of interconnected particles, said particles having an average diameter D.sub.P, wherein the openings of the casing are interconnected pores or channels having an average diameter of D.sub.M, wherein the container containing the plurality of filler elements is a bone substitute, wherein the individual filler elements have a diameter D.sub.Z, said diameter being defined by a longest enveloping circular cylinder, wherein the container comprises at least one window passing through the casing, and wherein the at least one window has a smallest diameter D.sub.F which is governed by formula D.sub.Z>D.sub.F>D.sub.P.

2. The bone substitute according to claim 1, wherein the average diameter D.sub.P of the particles is between 1 m and 250 m.

3. The bone substitute according to claim 1, wherein the average diameter D.sub.M of the pores or channels is less than D.sub.z.

4. The bone substitute according to claim 1, wherein the diameter D.sub.Z is larger than 200 m.

5. The bone substitute according to claim 1, wherein the diameter D.sub.F is larger than 50 m.

6. The bone substitute according to claim 1, wherein the filler elements and the casing are produced in one operation by means of a three-dimensional printing method or a selective laser-sintering process.

7. The bone substitute according to claim 1, wherein the filler elements are spaced apart from one another, and wherein a minimal distance between the filler elements is larger than 50 m.

8. The bone substitute according to claim 1, wherein the casing contains, in addition to the openings and the at least one window, a number of passages having a diameter D.sub.D which is at least equal in size to D.sub.P and is at least 30 m.

9. The bone substitute according to claim 1, wherein the casing has interparticle and intercrystalline interstices with an average diameter which is in a range of 0.1 D.sub.P to 0.5 D.sub.P, and is from 1 to 50 m.

10. The bone substitute according to claim 1, wherein the casing of the container and the filler elements are a reaction product of a solidification of a loose powder of the particles.

11. The bone substitute according to claim 10, wherein the casing of the container and the filler elements are a reaction product of a hydraulic cement after hardening.

12. The bone substitute according to claim 10, wherein the casing of the container and the filler elements are a melting product of a composite of a ceramic powder in a selective laser-sintering process.

13. The bone substitute according to claim 10, wherein the solidification is based on a reaction of one or more calcium phosphates or calcium sulfates with an aqueous solution.

14. The bone substitute according to claim 13, wherein the one or more calcium phosphates is selected from the group consisting of alpha-TCP, beta-TCP, hydroxyapatite, TetCP, and mixtures thereof.

15. The bone substitute according to claim 10, wherein the solidification takes place due to the reaction of: a) a powder mixture of MCP (Ca(H.sub.2PO.sub.4).sub.2) or MCPM (Ca(H.sub.2PO.sub.4).sub.2.H.sub.2O) or both; b) one or more of beta-TCP (Ca.sub.3(PO.sub.4).sub.2), alpha-TCP (Ca.sub.3(PO.sub.4).sub.2), hydroxyapatite (Ca.sub.5(PO.sub.4).sub.3OH), calcium-deficient hydroxyapatite (Ca.sub.10-x(HPO.sub.4).sub.x(PO.sub.4).sub.6-x(OH).sub.2-x, with 0x1), and tetra calcium phosphate (Ca.sub.4(PO.sub.4).sub.2O); and c) an aqueous solution or pure water.

16. The bone substitute according to claim 1, wherein the casing of the container and the filler elements are different reaction products of a solidification of a loose powder of the particles.

17. The bone substitute according to claim 1, the bone substitute contains DCPD, DCP or a mixture thereof.

18. The bone substitute according to claim 1, wherein a porosity of a filling of the container defined by the filler elements is in a range of 1 to 70%.

19. The bone substitute according to claim 1, wherein the filler elements have pores with an average diameter from 1 m to 50 m.

20. The bone substitute according to claim 1, wherein the casing is rotationally symmetrical.

21. The bone substitute according to claim 1, wherein the casing has a thickness d>D.sub.Z.

22. The bone substitute according to claim 1, wherein the bone substitute comprises a plurality of interconnected containers, which are arranged side by side or one above another.

23. The bone substitute according to claim 1, wherein the casing has one or more column-like protrusions projecting into the interior of the container.

24. The bone substitute according to claim 23, wherein the container in the interior has one or more transverse beams, which are connected to the casing at both ends.

25. A method for producing a bone substitute according to claim 1, wherein the casing of the container and the plurality of filler elements are produced simultaneously in layers by three-dimensional printing, selective laser-sintering or selective laser-sintering with ceramic.

26. The method according to claim 25, wherein layers produced by three-dimensional printing or by selective laser-sintering have a thickness of 10 m to 250 m.

27. The method of claim 25, wherein the filler elements are a reaction product of a hydraulic cement after hardening, and the hydraulic cement is formed of a powder consisting of MCP and MCPM and TCP and is hardened solely by means of water or an aqueous solution.

28. The method according to claim 25, wherein loose particles left behind inside the container by three-dimensional printing or by selective laser-sintering are removed through the at least one window from the container by vacuum, by rinsing with a medium in an ultrasonic bath, or by vibration.

29. The bone substitute according to claim 1, wherein there are no toxic components present in the bone substitute that would make it unsuitable for in vivo colonization with body cells or in vitro culture of cell tissues.

Description

(1) Preferably, the bone substitute is used for filling or bridging of defects or cavities in bone. The invention and further developments of the invention are explained in more detail below by means of partly diagrammatic representations of several exemplary embodiments.

(2) FIG. 1 shows a perspective view of an embodiment of the bone substitute according to the invention;

(3) FIG. 2 shows a plan view onto the embodiment of the bone substitute according to the invention shown in FIG. 1;

(4) FIG. 3 shows a longitudinal section through the embodiment of the bone substitute according to the invention shown in FIG. 1;

(5) FIG. 4 shows a cross-section through the embodiment of the bone substitute according to the invention shown in FIG. 1;

(6) FIG. 5 shows a side view of the embodiment of the bone substitute according to the invention shown in FIG. 1.

(7) FIG. 6 shows a perspective view of a further embodiment of the bone substitute according to the invention;

(8) FIG. 7 is a plan view of the embodiments of the bone substitute according to the invention shown in FIG. 6;

(9) FIG. 8 shows a longitudinal section through the embodiments of the bone substitute according to the invention shown in FIG. 6;

(10) FIG. 9 shows a cross section through the embodiment of the bone substitute according to the invention shown in FIG. 6; and

(11) FIG. 10 shows a side view of the embodiment of the bone substitute according to the invention shown in FIG. 6.

(12) FIGS. 1 to 5 show an embodiment of the bone substitute according to the invention 1 which essentially comprises a container 2 and a plurality of filler elements 5 which are enclosed in the container 2. The dimensions of the individual filler elements 5 are defined by their longest enveloping circular cylinder of diameter D.sub.z. The filler elements 5 consist of interconnected particles with an average diameter D.sub.P of at least 1 m. The diameter D.sub.Z of the longest circular cylinder enveloping a filler element 5 is larger than 200 m. The bone substitute 1 may comprise a plurality of interconnected containers 2, which are arranged side by side or one above the other. Furthermore, the bone substitute 1, may comprise, in addition to the plurality of filler elements 5 which are not connected to one another, a number of interconnected filler elements 5.

(13) The container 2 comprises a porous casing 4 which is at least partly provided with openings (not shown), which may have any shape but preferably is formed rotationally symmetrically (e.g., a hollow cylinder). The container 2 further has a container bottom 7, and a container top 8, wherein the container bottom 7 and the container top 8 may also be designed to be porous and at least partly with openings (not shown). The openings of the casing 4, of the container bottom 7 and of the container top 8 are interconnected pores or channels with an average diameter D.sub.M, which is smaller than D.sub.Z. Furthermore, the container 2 comprises a plurality of windows 6 passing through the casing 4, which are so dimensioned that no filler element 5 passes through one of the windows 6. For this purpose, the windows 6 have a smallest dimension D.sub.F governed by the formula D.sub.Z>D.sub.F>D.sub.P. The diameter D.sub.F of the windows 6 is larger than about 50 m.

(14) Furthermore, the casing 4 may additionally comprise several passages 3 in addition to the openings and the windows 6 (FIGS. 6 and 8 to 10), the diameter D.sub.D of which corresponds at least to the average diameter D.sub.P of the particles forming the filler elements 5 to enable removal of the loose powder, but ideally is larger than 30 m (angiogenesis). The casing 4 may comprise interparticle and intercrystalline interstices, which have an average diameter in the range of 0.1 D.sub.P to 0.5 D.sub.P, wherein the average diameter is between 1 and 50 m. The thickness d of the casing 4 may be smaller than the diameter D.sub.Z of the longest circular cylinders enveloping the filler elements 5. The casing 4 may have one or more column-like protrusions projecting into the interior of the container 2. In addition or alternatively, the container 2 can have one or more transverse beams, which are connected to the casing with both their ends. The porosity of the filling of the container 2 defined by filler elements 5 is in the range of 1 to 70%. The filler elements 5 are formed, for example, but not limited to, spherically and can have pores with an average diameter of 1 to 50 pm m.

(15) In addition to the conventional production methods, so-called SFF methods (Solid Free Form Fabrication) are known for producing bone substitute materials. In these so-called SFF methods the geometry is freely definable.

(16) The present invention relates primarily to an application using the powder-based 3DP method (Three-Dimensional Printing) but also directly applicable to other powder-based SFF methods such as SLS (Selective Laser Sintering).

(17) In the 3DP method, so-called 3D printers are used which include machines that build up three-dimensional work pieces. The work pieces are usually built under computer control from one or more liquid or powdered materials according to predetermined dimensions and shapes which can be defined by the CAD methods. The 3DP method is an additive method, wherein a work piece is produced by successively forming layers of material. In addition, physical or chemical hardening processes take place when building the work piece. For producing the work piece, the dimensions and shape are read by the machine and then the individual layers of liquid, powder, or plate-like material are successively deposited so that a work piece made of a series of cross-sectional layers is formed. To produce the work piece, these layers are automatically connected or fused together.

(18) The SLS method is also an additive method, wherein three-dimensional structures are produced from a powdered starting material by sintering. The work piece is also built up layer by layer, wherein small particles of plastic, metal or ceramic are melted by means of high energy lasers (carbon dioxide laser). The material is selectively melted on the surface of a powder bed, so that a solid cross-sectional layer of the work piece is formed after hardening of the molten material. After a layer is complete, the powder bed is lowered by one layer thickness and a new layer of material is applied to the surface of the lowered powder bed. The process is repeated until the work piece is completed.

(19) In one embodiment of the method according to the invention for producing the bone substitute 1, the casing 4 of the container 2 and the plurality of filler elements 5 are produced simultaneously in layers by means of 3DP or SLS methods. The layers produced by the 3DP or SLS method can have a thickness of 10 m to 250 m, preferably 30 m-10 m. Furthermore, the particles of the hydraulic cement forming the powder may consist of MCPM (Ca(H.sub.2PO.sub.4).sub.2.H.sub.2O) or MCP (Ca(H.sub.2PO.sub.4).sub.2) and TCP and may be hardened solely by means of an aqueous solution or water. The loose particles left behind inside the container by the 3DP method or the SLS method and which have not hardened can be removed through at least one window 6 from the container 2 by applying one of the following techniques:

(20) vacuum, rinsing with a medium in an ultrasonic bath or vibration.

(21) Below, for the sake of simplicity, only the 3DP method is mentioned. However, this implies also alternative methods. Although the geometry is freely definable in these methods, undercut and overhanging and nested geometries must be supported, since the structure is built in layers. This in turn requires a later removal of these supports. In the case of 3DP and SLS the support function is taken over by loose powder, which has to be removed again later (depowdering). Nowadays, this is done normally with air pressure in the case of parts produced by 3DP and SLS. For this purpose, an airbrush nozzle is used, blowing filtered compressed air onto the bone substitute according to the invention. This will free from the outside the bone substitute produced according to the invention step by step from loose particles of the powder used. In particular, inside the bone substitute produced according to the invention this is done only with difficulties. Therefore, in SFF methods, the geometrical freedom in the interior is limited by the freedom of the removal of the free powder. If the remaining unhardened powder cannot be removed, the geometry is lost. In practice, this limits severely the choice of the geometry especially in the interior of a body. Typically, large channels have to be built, enabling a depowdering. The present invention focuses heavily on a better solution for the depowdering which thereby makes possible a new type of bone substitute. Moreover, this method allows for efficient and economical production.

(22) Another inventive novelty relates to the composition of the powder. The prior art in 3DP for bone substitute is the following: An acid is applied onto the powder bed by means of a print head, whereby the ceramic powder particles are joined locally by means of a precipitation reaction. A novel method by mixing the ceramic particles (e.g., CaP calcium phosphates) with the particles which on contact with water form acid (e.g., MCP mono-calcium phosphate) allows printing with water. In addition to precise adjustment of the calcium/phosphate ratio this offers other advantages, described below in terms of the mechanical properties and the production method. One way to improve the mechanical properties of bone substitute according to the invention further lies in so-called post-hardening steps, i.e., the bone substitute produced according to the invention is, for example, enhanced by immersion in an acid bath, by thermal post-treatment, e.g., by sintering, or by chemical post-treatment (infiltration). In the case of the novel printing with a water-based and acid-free solution on a CaP/MCP powder bed, therefore, a new and completely unproblematic post-hardening is possible by solidifying the bone substitute at controlled or saturated humidity or by direct contact with water (with capillary soaking, immersing or spraying) by subsequent crystal formation.

(23) The casing 4 of the container 2 and the filler elements 5 may be the reaction product of the solidification of a loose powder of the particles and are produced by means of 3DP or SLS. Examples include a) solidification by crystal formation or polymerization (e.g., sugar or salt powder+water from the print head or as a further alternative, any powder+salt/sugar/polymer solution from the print head (e.g., sugar/CaP powder bed is sprayed locally with water droplets (from the print head via 3DP). Interlocking of the sugar crystals forms a matrix which holds together the CaP particles. Subsequent steps could include a further composite of CaP or washing out of the sugar crystals; b) solidification by capillary forces: drying and interlocking of the surface of a powder; c) solidification by gelation (e.g. alginate+Ca.sup.2+ ions=gel); d) solidification by cooling (e.g., a liquid medium is printed on a powder and solidifies by cooling); or e) solidification by sintering or melting and cooling (SLS or SLM (Selective Laser Melting) method.

(24) Alternatively, the casing 4 of the container 2 and the filler elements 5 may be the reaction product of a hydraulic cement after its hardening, preferably produced by 3DP, but also the reaction product of the composite of a, e.g., ceramic and polymer powder mixture in a SLS process.

(25) Furthermore, the solidification may be based on the reaction of one or more calcium phosphates, or calcium sulfates with an aqueous solution. Here, the calcium phosphate may be alpha-TCP, beta-TCP, hydroxyapatite, TetCP, or a mixture thereof.

(26) In alternative embodiments the solidification can take place due to the reaction of a) a powder mixture of MCP (Ca(H.sub.2PO.sub.4).sub.2) or MCPM (Ca(H.sub.2PO.sub.4).sub.2.H.sub.2O) or a mixture thereof with b) one or more of the following substances: beta-TCP (Ca.sub.3(PO.sub.4).sub.2) or alpha-TCP (Ca.sub.3(PO.sub.4).sub.2) or hydroxyapatite (Ca.sub.5(PO.sub.4).sub.3OH) or calcium-deficient hydroxyapatite (Ca.sub.10-x(HPO.sub.4).sub.x(PO.sub.4).sub.6-x(OH).sub.2-x, with 0x1) or tetra calcium phosphate (Ca.sub.4(PO.sub.4).sub.2O), and c) an aqueous solution or pure water.

(27) The embodiment shown in FIGS. 6 to 10 of the bone substitute 1 according to the invention differs from the embodiment described in FIG. 1-5 only in that that the filler elements 5 are T-shaped or mushroom-shaped. Here, the filler elements 5 may comprise two essentially circular cylindrical portion, of which a respective first portion having a larger diameter than the adjoining second portion. Differently configured embodiments of the filler elements 5 are also possible and can be combined at will.

(28) Although, as described above, various embodiments of the present invention are present, they are to be understood that the various features can be used both individually and in any combination.

(29) This invention is therefore not just limited to the aforementioned particularly preferred embodiments.