Bone substitute and method for producing the same

• US 9,907,654 B2
• Filed: 12/11/2012
• Issued: 03/06/2018
• Est. Priority Date: 12/11/2012
• Status: Active Grant

• Current Assignee: Dr. H.C. Robert Mathys Stiftung
• Original Assignee: Dr. H.C. Robert Mathys Stiftung
• Inventors: Butscher, Andre, Bohner, Marc, Dbelin, Nicola
• Primary Examiner(s): Stewart, Alvin
• Application Number:
  US14/650,495
• Publication Number:
  US 20150297349A1
• Time in Patent Office: 1,911 Days
• Field of Search: 623 2361, 623 2375, 623 2355, 623 2372
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30199 Three-dimensional shapes
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30588 filled with solid particles
• CPC Class Codes: A61F 2002/30784 Plurality of holes
• CPC Class Codes: A61F 2002/30968 Sintering
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: B29C 64/165 using a combination of solid and fluid materials, e.g. a powder selectively bound by a liquid binder, catalyst, inhibitor or energy absorber
• CPC Class Codes: B29L 2031/7532 Artificial members, protheses
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

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_p; and D) the openings of the casing (4) are interconnected pores or channels with an average diameter of D_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_P,

wherein the openings of the casing are interconnected pores or channels having an average diameter of D_M,

wherein the container containing the plurality of filler elements is a bone substitute,

wherein the individual filler elements have a diameter D_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_F which is governed by formula D_Z>

D_F>

D_P.

2. The bone substitute according to claim 1, wherein the average diameter D_P of the particles is between 1 μ

m and 250 μ

m.

3. The bone substitute according to claim 1, wherein the average diameter D_M of the pores or channels is less than D_z.

4. The bone substitute according to claim 1, wherein the diameter D_Z is larger than 200 μ

m.

5. The bone substitute according to claim 1, wherein the diameter D_F is larger than 50 μ

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 μ

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_D which is at least equal in size to D_P and is at least 30 μ

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_P to 0.5 D_P, and is from 1 to 50 μ

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(H₂PO₄)₂) or MCPM (Ca(H₂PO₄)₂.H₂O) or both;

b) one or more of

beta-TCP (Ca₃(PO₄)₂),

alpha-TCP (Ca₃(PO₄)₂),

hydroxyapatite (Ca₅(PO₄)₃OH),

calcium-deficient hydroxyapatite (Ca_10-x(HPO₄)_x(PO₄)_6-x(OH)_2-x, with 0≦

x≦

1), and

tetra calcium phosphate (Ca₄(PO₄)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 μ

m to 50 μ

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_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 μ

m to 250 μ

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.