BONE REPLACEMENT MATERIALS

• US 20070203584A1
• Filed: 02/14/2007
• Published: 08/30/2007
• Est. Priority Date: 02/14/2006
• Status: Active Grant

• Current Assignee: Washington State University
• Original Assignee: Washington State University
• Inventors: Bose, Susmita, Bandyopadhyay, Amit
• Granted Patent: US 9,327,056 B2
• Time in Patent Office: Days
• US Class Current: 623/23.500
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/30942 for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
• CPC Class Codes: A61F 2/36 Femoral heads ; Femoral endoprostheses
• CPC Class Codes: A61F 2/367 Proximal or metaphyseal parts of shafts trochanteric devices connected to said proximal parts A61F2/30739
• CPC Class Codes: A61F 2/3676 Distal or diaphyseal parts of shafts
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/30004 the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
• CPC Class Codes: A61F 2002/30006 differing in density or specific weight
• CPC Class Codes: A61F 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30028 differing in tissue ingrowth capacity, e.g. made from both ingrowth-promoting and ingrowth-preventing parts
• CPC Class Codes: A61F 2002/30115 circular-O-shaped
• CPC Class Codes: A61F 2002/30118 concentric circles
• CPC Class Codes: A61F 2002/30179 X-shaped
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30235 tubular, e.g. sleeves
• CPC Class Codes: A61F 2002/30322 differing in surface structures
• CPC Class Codes: A61F 2002/30593 hollow
• CPC Class Codes: A61F 2002/30616 Sets comprising a plurality of prosthetic parts of different sizes or orientations
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30838 : Microstructures
• CPC Class Codes: A61F 2002/30909 : Nets
• CPC Class Codes: A61F 2002/3093 : for promoting ingrowth of bone tissue
• CPC Class Codes: A61F 2002/3097 : using laser
• CPC Class Codes: A61F 2230/0006 : circular
• CPC Class Codes: A61F 2230/0058 : X-shaped
• CPC Class Codes: A61F 2230/0069 : cylindrical
• CPC Class Codes: A61F 2250/0014 : having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61F 2250/0023 : differing in porosity
• CPC Class Codes: A61F 2250/0026 : differing in surface structures
• CPC Class Codes: A61F 2310/00017 : Iron- or Fe-based alloys, e.g. stainless steel
• CPC Class Codes: A61F 2310/00023 : Titanium or titanium-based alloys, e.g. Ti-Ni alloys
• CPC Class Codes: A61F 2310/00029 : Cobalt-based alloys, e.g. Co-Cr alloys or Vitallium
• CPC Class Codes: A61F 2310/00047 : Aluminium or Al-based alloys
• CPC Class Codes: A61F 2310/00053 : Vanadium or V-based alloys
• CPC Class Codes: A61F 2310/00113 : Silver or Ag-based alloys
• CPC Class Codes: A61F 2310/00155 : Gold or Au-based alloys
• CPC Class Codes: A61F 2310/00179 : Ceramics or ceramic-like structures
• CPC Class Codes: A61F 2310/00185 : based on metal oxides
• CPC Class Codes: A61F 2310/00227 : containing titania or titanium oxide
• CPC Class Codes: A61F 2310/00293 : containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 2300/404 : Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 : Antibiotics
• CPC Class Codes: A61L 2300/414 : Growth factors
• CPC Class Codes: A61L 2430/02 : for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/06 : Titanium or titanium alloys
• CPC Class Codes: A61L 27/42 : having an inorganic matrix
• CPC Class Codes: A61L 27/427 : of other specific inorganic materials not covered by A61L27/422 or A61L27/425
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: B22F 10/25 : Direct deposition of metal particles, e.g. direct metal deposition [DMD] or laser engineered net shaping [LENS]
• CPC Class Codes: B22F 10/366 : Scanning parameters, e.g. hatch distance or scanning strategy
• CPC Class Codes: B22F 2207/17 : density or porosity gradients
• CPC Class Codes: B22F 2998/00 : Supplementary information concerning processes or compositions relating to powder metallurgy
• CPC Class Codes: B22F 3/105 : by using electric current other than for infrared radiant energy, laser radiation or plasma B22F3/11 takes precedence; by ultrasonic bonding B22F3/115 takes precedence
• CPC Class Codes: B22F 3/1109 : Inhomogenous pore distribution composite layers of porous nature B22F7/002
• CPC Class Codes: B22F 3/1125 : involving a foaming process
• CPC Class Codes: B22F 3/1146 : After-treatment maintaining the porosity B22F3/114 takes precedence
• CPC Class Codes: B23K 2103/14 : Titanium or alloys thereof
• CPC Class Codes: B23K 2103/16 : Composite materials , e.g. fibre reinforced
• CPC Class Codes: B23K 26/0006 : taking account of the properties of the material involved B23K26/32, B23K26/40 take precedence
• CPC Class Codes: B23K 26/342 : Build-up welding
• CPC Class Codes: B23K 26/70 : Auxiliary operations or equipment
• CPC Class Codes: B33Y 10/00 : Processes of additive manufacturing
• CPC Class Codes: B33Y 50/00 : Data acquisition or data processing for additive manufacturing
• CPC Class Codes: B33Y 70/10 : Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: Y02P 10/25 : Process efficiency

Abstract

Particular aspects provide novel devices for bone tissue engineering, comprising a metal or metal-based composite member/material comprising an interior macroporous structure in which porosity may vary from 0-90% (v), the member comprising a surface region having a surface pore size, porosity, and composition designed to encourage cell growth and adhesion thereon, to provide a device suitable for bone tissue engineering in a recipient subject. In certain aspects, the device further comprises a gradient of pore size, porosity, and material composition extending from the surface region throughout the interior of the device, wherein the gradient transition is continuous, discontinuous or seamless and the growth of cells extending from the surface region inward is promoted. Additional aspects provide a device for bone tissue engineering, comprising a metal or metal-based composite member/material comprising an interior porous structure, wherein the pore size, porosity and material composition is selected to provide a device having an optimal density and/or elastic modulus and/or compression strength for a specific recipient. Novel methods for fabricating the devices are also provided.

Claims

1. A device for bone tissue engineering, comprising a metal or metal-based composite member/material comprising an interior macroporous structure in which porosity may vary from 0-90 vol %, the member comprising a surface region having a surface pore size, porosity, and composition designed to encourage cell growth and adhesion thereon, to provide a device suitable for bone tissue engineering in a recipient subject.

2. The device of claim 1, further comprising a gradient of pore size, porosity, and material composition extending from the surface region into or throughout the interior of the device, wherein the gradient transition is continuous or seamless and the growth of cells extending from the surface region inward is promoted.

3. The device of claim 1, wherein the member/material comprises at least one material selected from the group consisting of:

titanium (Ti);

commercially pure Ti;

alpha Ti alloys;

beta Ti alloys;

aluminum (Al);

iron (Fe);

vanadium (V));

Ti alloys and their intermetallics with major alloying elements including Al, V, Nb, Fe, Zr, Mo, O, Ni, Cr, Co;

Ta forming alloys including Ti6Al4V, Ti-6Al-7Nb, Ti-5Al-2.5Fe, Ti-12Mo-6Zr-2Fe, Ti-15Mo-5Zr-3Al, Ti-15Mo-3Nb-30, Ti-13Nb-13Zr, Ti-35Nb-5Ta-7Zr;

Stainless steel, CoCrMO;

ceramics, metal oxides including TiO₂, calcium based inorganic salt including calcium phosphates, calcium carbonates, silver and silver oxides, gold, and combinations thereof.

4. The device of any one of claims 1-3, wherein the composite member/material or a portion of the surface region thereof comprises a material composition of metal and ceramic in a gradient or continuous or seamless gradient from a position on the exterior surface having a highest ceramic content, transitioning to lowest or zero ceramic content at an interior structure position composed of metal or metal-based composite.

5. The device of claim 4, wherein the ceramic portion comprises an inorganic salt.

6. The device of claim 5, wherein the inorganic salt comprises a form of calcium selected from the group consisting of calcium phosphates and calcium carbonates, and combinations thereof.

7. The device of any one of claims 1-3, wherein the surface region comprises nanoscale or microscale pores ranging from about 1 nm to about 500 nm in diameter, or from about 1 nm to about 1 μ

m.

8. The device of any one of claims 1-3, wherein the member/material structure comprises a microporous or macroporous pattern having pore sizes in the range of about 1 μ

m to about 5 mm.

9. The device of any one of claims 1-3, further comprising a chemical or biological agent deposited in or on the composite member/material or in one or more pores thereof to operatively provide for release or controlled release of the agent within a recipient.

10. The device of claim 9, wherein the chemical or biological agent is deposited in or on one or more surface structures or pores thereof.

11. The device of claim 9, wherein the agent comprises at least one agent suitable to provide a beneficial biological or physiological effect.

12. The device of claim 11, wherein the at least one agent suitable to provide a beneficial biological or physiological effect comprises an antimicrobial agent.

13. The device of claim 11, wherein the agent comprises at least one agent selected from the group consisting of antibiotics, growth factors, and drugs.

14. The device of any one of claims 1-3, wherein at least one of the pore size, porosity and material composition is selected to provide a device having an optimal density, elastic modulus or compression strength for a specific recipient.

15. The device of claim 14, wherein the macroporous structure is selected to provide a device having an optimal density, elastic modulus or compression strength for a specific recipient.

16. A device for bone tissue engineering, comprising a metal or metal-based composite member/material comprising an interior porous structure, wherein at least one of the pore size, porosity and material composition is selected to provide a device having an optimal density for a specific recipient.

17. A device for bone tissue engineering, comprising a metal or metal-based composite member/material comprising an interior porous structure, wherein at least one of the pore size, porosity and material composition is selected to provide a device having an optimal elastic modulus for a specific recipient.

18. A device for bone tissue engineering, comprising a metal or metal-based composite member/material comprising an interior porous structure, wherein at least one of the pore size, porosity and material composition is selected to provide a device having an optimal compression strength for a specific recipient.

19. A method of producing a porous metal or metal-based composite device for bone tissue engineering, comprising:

obtaining input from bone imaging scans of a specific patient to provide input data;

entering the input data or values derived therefrom into a fabrication machine;

fabricating a porous bone tissue engineering device with the fabrication machine based on the input data, wherein at least one of the density, the modulus of elasticity and the compression strength of the member/material is selected to provide a device having at least one of an optimal density, elastic modulus and compression strength for a specific recipient.

20. The method of claim 19, wherein the device comprises surface modifications to encourage cell growth and adhesion thereon.

21. The method of claim 19, wherein the fabrication machine consists of or comprises a Laser Engineered Net Shaping (LENS) apparatus.

22. The method of claim 19, wherein fabrication comprises fabrication of a device comprising a porous metal or metal-based composite.

23. A device for bone tissue engineering formed by the method of claim 19.

24. A method of producing a device for bone tissue engineering, comprising:

selecting a solid freeform fabrication technique; and

fabricating, using the fabrication technique, a metal or metal-based composite member/material comprising an interior macroporous structure in which porosity may vary from 0-90 vol %, wherein the member/material comprises a surface region having at least one of a surface pore size, porosity, and composition designed to encourage cell growth and adhesion thereon, to provide a device suitable for bone tissue engineering in a recipient subject.

25. The method of claim 24, further comprising making a gradient of pore size, porosity, and material composition extending from the surface region into or throughout the interior of the device, wherein the gradient transition is continuous or seamless and suitable to operatively promote the growth of cells extending from the surface region inward.

26. The method of claim 24, wherein the member/material comprises at least one material selected from the group consisting of:

titanium (Ti);

commercially pure Ti;

alpha Ti alloys;

beta Ti alloys;

aluminum (Al);

iron (Fe);

vanadium (V));

Ti alloys and their intermetallics with major alloying elements including Al, V, Nb, Fe, Zr, Mo, O, Ni, Cr, Co;

Ta forming alloys including Ti6Al4V, Ti-6Al-7Nb, Ti-5Al-2.5Fe, Ti-12Mo-6Zr-2Fe, Ti-15Mo-5Zr-3Al, Ti-15Mo-3Nb-30, Ti-13Nb-13Zr, Ti-35Nb-5Ta-7Zr;

Stainless steel, CoCrMO;

ceramics, metal oxides including TiO₂, calcium based inorganic salt including calcium phosphates, calcium carbonates, silver and silver oxides, gold, and combinations thereof.

27. The method of any one of claims 24-26, wherein the freeform fabrication technique consists of or comprises Laser Engineered Net Shaping (LENS).

28. The method of any one of claims 24-26, wherein the surface region comprises nanoscale or microscale pores ranging from about 1 nm to about 500 nm in diameter, or from about 1 nm to about 1 μ

m diameter, suitable to operatively facilitate cell growth and/or adhesion thereon.

29. The method of claim 28, wherein the surface region comprising the nanoscale or microscale pores is positioned to be operatively in contact with or be inserted into a bone upon implant of the member/material.

30. The method of claim 28, wherein the surface region comprising the nanoscale or microscale pores is fabricated by electrochemical etching and/or chemical dissolution, which may be preformed simultaneously or in sequence.

31. The method of any one of claims 24-26, wherein the composite member/material or a portion of the surface region thereof comprises a material composition of metal and ceramic in a gradient or continuous or seamless gradient from a position on the exterior surface having a highest ceramic content, transitioning to lowest or zero ceramic content at an interior structure position composed of metal or metal-based composite.

32. The method of claim 31, wherein the ceramic portion comprises an inorganic salt.

33. The method of claim 32, wherein the inorganic salt comprises a form of calcium selected from the group consisting of calcium phosphates and calcium carbonates, and combinations thereof.

34. The method of any one of claims 24-26, wherein the member/material structure comprises a microporous or macroporous pattern having pore sizes in the range of about 1 μ

m to about 5 mm.

35. The method of any one of claims 24-26, further comprising a chemical or biological agent deposited in or on the composite member/material or in one or more pores thereof to operatively provide for release or controlled release of the agent within a recipient.

36. The method of claim 35, wherein the chemical or biological agent is deposited in or on one or more surface structures or pores thereof.

37. The method of claim 35, wherein the agent comprises at least one agent suitable to provide a beneficial biological or physiological effect.

38. The method of claim 35, wherein the at least one agent suitable to provide a beneficial biological or physiological effect comprises an antimicrobial agent.

39. The method of claim 35, wherein the agent comprises at least one agent selected from the group consisting of antibiotics, growth factors, and drugs.