Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal

• US 20050272153A1
• Filed: 01/27/2005
• Published: 12/08/2005
• Est. Priority Date: 01/27/2004
• Status: Abandoned Application

• Current Assignee: Cody Bunger, Haisheng Li, Zou Xuenong
• Original Assignee: Cody Bunger, Haisheng Li, Zou Xuenong
• Inventors: Xuenong, Zou, Li, Haisheng, Bunger, Cody
• Application Number:
  US11/045,620
• Publication Number:
  US 20050272153A1
• Time in Patent Office: Days
• US Class Current: 435/395
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30767 Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/32 for the hip
• CPC Class Codes: A61F 2/34 Acetabular cups
• CPC Class Codes: A61F 2/36 Femoral heads ; Femoral endoprostheses
• CPC Class Codes: A61F 2/38 for elbows or knees
• CPC Class Codes: A61F 2/44 for the spine, e.g. vertebrae, spinal discs
• CPC Class Codes: A61F 2/4644 Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material bone material A61F2/28; disintegrating or milling devices B02C
• CPC Class Codes: A61F 2002/0086 for preferentially controlling or promoting the growth of specific types of cells or tissues of bone tissue onto implantable joints A61F2002/3093
• 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 2002/2835 Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/30199 Three-dimensional shapes
• CPC Class Codes: A61F 2002/30225 Flat cylinders, i.e. discs
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/3093 for promoting ingrowth of bone tissue
• CPC Class Codes: A61F 2002/4648 Means for culturing bone graft
• CPC Class Codes: A61F 2230/0063 Three-dimensional shapes
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2310/00161 Carbon; Graphite
• CPC Class Codes: A61F 2310/00293 : containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00341 : Coral, e.g. aragonite, porite
• CPC Class Codes: A61F 2310/00491 : Coating made of niobium or Nb-based alloys
• CPC Class Codes: A61F 2310/00544 : Coating made of tantalum or Ta-based alloys
• CPC Class Codes: A61F 2310/00976 : Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF
• CPC Class Codes: A61F 2310/00982 : Coating made of collagen
• CPC Class Codes: A61L 2300/222 : Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/252 : Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/606 : Coatings
• CPC Class Codes: A61L 2300/64 : Animal cells
• CPC Class Codes: A61L 2400/18 : Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2430/00 : Materials or treatment for tissue regeneration
• CPC Class Codes: A61L 27/00 : Materials for grafts or prostheses or for coating grafts or prostheses dental prostheses A61C13/00; shape or structure of prostheses A61F2/00; use of preparations for artificial teeth A61K6/80; artificial kidneys A61M1/14
• CPC Class Codes: A61L 27/20 : Polysaccharides
• CPC Class Codes: A61L 27/22 : Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/3608 : Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 : Bones
• CPC Class Codes: A61L 27/38 : containing added animal cells organs or tissue containing native cells A61L27/36
• 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: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0662 : Stem cells

Abstract

Adult autologous stem cells cultured on a porous, three-dimensional tissue scaffold-implant for bone regeneration by the use of a hyaluronan and/or dexamethasone to accelerate bone healing alone or in combination with recombinant growth factors or transfected osteogenic genes. The scaffold-implant may be machined into a custom-shaped three-dimensional cell culture system for support of cell growth, reservoir for peptides, recombinant growth factors, cytokines and antineoplastic drugs in the presence of a hyaluronan and/or dexamethasone alone or in combination with growth factors or transfected osteogenic genes, to be assembled ex vivo in a tissue incubator for implantation into bone tissue.

Claims

1. A three-dimensional tissue scaffold-implant for supporting tissue on-growth, the scaffold-implant comprising:

a lattice having a matrix of interconnected pores which form surfaces in three dimensions;

an inert, bio-compatible material covering the surfaces; and

at least one of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor, covering the material.

2. The tissue scaffold-implant of claim 1, wherein the inert, biocompatible material comprises a metal.

3. The tissue scaffold-implant of claim 2, wherein the metal comprises tantalum.

4. The tissue scaffold-implant of claim 1, wherein the inert, biocompatible material comprises a metal alloy.

5. The tissue scaffold-implant of claim 1, further comprising living cells covering the biocompatible material, the cells selected from the group consisting of bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, gene transfected cells, endothelial cells and combinations thereof.

6. The tissue scaffold-implant of claim 1, further comprising tissue grown over the bio-compatible material.

7. The tissue scaffold-implant of claim 6, wherein the tissue comprises bone.

8. A method of forming tissue, the method comprising:

providing a three-dimensional tissue scaffold comprising a lattice having a matrix of interconnected pores which form surfaces in three dimensions, and an inert, biocompatible material covering the surfaces;

covering the material covered surfaces of the scaffold with living cells; and

culturing the scaffold to grow tissue on and in the scaffold.

9. The method of claim 8, wherein prior to the culturing step, further comprising the step of applying at least one of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor, to the material covered surfaces.

10. The method of claim 9, wherein the applying step includes encapsulating the at least one of the hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokines therapeutic agent, chitosan, polymer, osteogenic gene and growth factor.

11. The method of claim 10, wherein the encapsulation is performed by complex sandwich conjugation with a polymeric material.

12. The method of claim 11, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.

13. The method of claim 12, further comprising the step of implanting the scaffold in a body of one of an animal and a human being.

14. The method of claim 9, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.

15. The method of claim 10, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.

16. The method of claim 8, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.

17. The method of claim 16, further comprising the step of implanting the scaffold in a body of one of an animal and a human being.

18. The method of claim 8, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.

19. The method of claim 8, wherein the covering step is performed by cell transplantation.

20. The method of claim 8, wherein the inert, biocompatible metal comprises tantalum.

21. The method of claim 8, wherein the living cells are selected from the group consisting of bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, gene transfected cells, endothelial cells and combinations thereof.

22. The method of claim 8, wherein the tissue comprises bone.

23. A method of making an implant for supporting tissue on-growth, the method comprising:

providing a three-dimensional tissue scaffold comprising a lattice having a matrix of interconnected pores which form surfaces in three dimensions, and an inert, biocompatible metal covering the surfaces; and

covering the metal covered surfaces of the scaffold with living cells.

24. The method of claim 23, further comprising the step of applying at least one of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor, to the metal covered surfaces.

25. The method of claim 24, wherein the applying step includes encapsulating at least one of the hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokines, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor.

26. The method of claim 25, wherein the encapsulation is performed by complex sandwich conjugation with a polymeric material.

27. The method of claim 26, further comprising the step of culturing the scaffold to grow tissue on and in the scaffold.

28. The method of claim 27, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.

29. The method of claim 23, further comprising the step of culturing the scaffold to grow tissue on and in the scaffold.

30. The method of claim 29, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.

31. The method of claim 25, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.

32. The method of claim 23, wherein the covering step is performed by cell transplantation.

33. The method of claim 23, wherein the inert, biocompatible material comprises tantalum.

34. The method of claim 23, wherein the living cells are selected from the group consisting of bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, gene transfected cells, endothelial cells and combinations thereof.

35. The method of claim 34, wherein cells are encapsulated in at least one of a hyaluronan and collagen, or chitosan with a polymeric material by complex sandwich conjugation.

36. The method of claim 28, wherein the culturing method is performed in one of or any combination of a static, dynamic medium flow, pulsatile flow, microgravity and multidirectional gravity culturing environment.

37. The method of claim 23, wherein the tissue comprises bone.