Method and device for producing biological tissue in a growth chamber

• US 20040096430A1
• Filed: 11/10/2003
• Published: 05/20/2004
• Est. Priority Date: 12/12/2000
• Status: Abandoned Application

• Current Assignee: Jorg Bauer
• Original Assignee: Jorg Bauer
• Inventors: Bauer, Jorg
• Application Number:
  US10/450,478
• Publication Number:
  US 20040096430A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/44 for the spine, e.g. vertebrae, spinal discs
• CPC Class Codes: A61F 2002/0086 for preferentially controlling or promoting the growth of specific types of cells or tissues
• 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 2002/30057 made from both cortical and cancellous adjacent parts
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30762 Means for culturing cartilage
• 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 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• 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: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 35/00 Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion machines for extracting juice from animal or plant tissue by electroplasmolysis A23N1/006, processes employing electric or wave energy B01J19/08; treatment of microorganisms or enzymes with electrical or wave energy C12N13/00; methods for cell fusion C12N15/02; introduction of foreign genetic material C12N15/87
• CPC Class Codes: C12N 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2533/18 Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 2533/54 : Collagen; Gelatin
• CPC Class Codes: C12N 5/0654 : Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth

Abstract

The invention relates to a method and a device for producing tissue in a growth chamber for transplantation into or onto a human or animal body. The invention can be used particularly advantageously for the cultivation of structured functional bones. Biological cells are applied to a growth framework and both are arranged in a growth chamber. The structured and functional cultivation is achieved by allowing biologically active stimuli, for example mechanical, electrical, magnetic, chemical, olfactory, acoustic and/or optical stimuli, to act in a specified manner, in particular at different times or in different locations or in different ways. It has been found that the action of stimuli which correspond to those to which corresponding natural tissue in the body is naturally exposed is the most suitable.

Claims

1. A method for producing biological tissue in a growth chamber, in particular for transplantation into or onto a human or animal body, comprising

applying biological cells to a growth framework, said growth framework defining an initial form of the tissue to be produced,

arranging the biological cells and the growth framework in the growth chamber, and

exerting a biologically active stimulus on the growth framework and/or on the biological cells.

2. The method as claimed in claim 1, wherein the stimulus corresponds to or is at least similar to a stimulus to which the tissue is naturally exposed in or on the body.

3. The method as claimed in claim 1 or 2, wherein structured and/or functional biological tissue is produced.

4. The method as claimed in one of the preceding claims, wherein growth, form, function, structure and/or nature of the biological tissue is influenced by the stimulus or a sequence of stimuli.

5. The method as claimed in one of the preceding claims, wherein different stimuli and/or different kinds of stimuli are exerted and cell-differentiated tissue sections are produced.

6. The method as claimed in one of the preceding claims, wherein the growth framework, at the start of the method, essentially defines only an initial form of the tissue to be produced.

7. The method as claimed in one of the preceding claims, wherein an organ, a bone, a cartilage, a blood vessel, periosteum, or a functional combination of these, is produced.

8. The method as claimed in one of the preceding claims, wherein the grown tissue essentially determines the biomechanical properties of the arrangement of tissue and growth framework.

9. The method as claimed in one of the preceding claims, wherein a framework is used comprising resorbable material, in particular biological material or cells.

10. The method as claimed in one of the preceding claims, wherein a framework is used comprising a material that promotes cell growth, in particular cellulose, starch, alcohol compounds, gel and/or gel-like material.

11. The method as claimed in one of the preceding claims, wherein the growing tissue takes the place of the growth framework.

12. The method as claimed in one of the preceding claims, wherein a framework is used comprising nonresorbable material and/or electrically conductive material.

13. The method as claimed in one of the preceding claims, wherein the framework is separated from the tissue which has grown from the biological cells on the framework.

14. The method as claimed in one of the preceding claims, wherein a pharmacologically active substance, preferably a growth-promoting substance, particularly preferably a bone morphogenetic protein, a fibrogen and/or a genetically modified substance is added.

15. The method as claimed in one of the preceding claims, wherein a depot of a pharmacologically active substance is placed on and/or in the growth framework and/or the tissue.

16. The method as claimed in claim 15, wherein the pharmacologically active substance is released after transplantation of the tissue into or onto the body.

17. The method as claimed in one of the preceding claims, wherein mechanical, electrical, magnetic, chemical, olfactory, acoustic and/or optical stimuli are exerted on the growth framework and/or on the tissue.

18. The method as claimed in one of the preceding claims, wherein stimuli which can be changed in terms of their timing, in particular discontinuous stimulating impulses and/or periodic stimuli, are exerted on the growth framework and/or on the biological cells.

19. The method as claimed in one of the preceding claims, wherein biologically active stimuli are exerted with a piezoelectric material.

20. The method as claimed in one of the preceding claims, wherein a piezoelectric means is arranged on and/or in the growth framework.

21. A growth framework for producing biological tissue, in particular for transplantation into or onto a human or animal body, and in particular for use of the method as claimed in one of the preceding claims, in which

the growth framework defines an initial form of the tissue to be produced,

the growth framework can be arranged in a growth chamber,

biological cells can be applied to the growth framework, and

a biologically active stimulus can be exerted on the growth framework and/or on the biological cells.

22. The growth framework as claimed in claim 21, wherein biological tissue with functional structure can be produced or cultivated.

23. The growth framework as claimed in one of the preceding claims, wherein the growth framework essentially defines only an initial form of the biological tissue.

24. The growth framework as claimed in one of the preceding claims, wherein different stimuli and/or different kinds of stimuli can be exerted.

25. The growth framework as claimed in one of the preceding claims, wherein growth, form, function, structure and/or nature of the tissue can be influenced by the stimulus or a sequence of stimuli.

26. The growth framework as claimed in one of the preceding claims, wherein the biological tissue comprises an organ, a bone, a cartilage, a blood vessel, periosteum, or a functional combination of these.

27. The growth framework as claimed in one of the preceding claims, wherein the grown tissue essentially determines the biomechanical properties of the arrangement of tissue and growth framework.

28. The growth framework as claimed in one of the preceding claims, wherein resorbable material is used, in particular biological material or cells.

29. The growth framework as claimed in one of the preceding claims, wherein a material that promotes cell growth is used, in particular cellulose, starch, alcohol compounds, gel and/or gel-like material.

30. The growth framework as claimed in one of the preceding claims, wherein its place can be taken by the growing tissue.

31. The growth framework as claimed in one of the preceding claims, wherein it comprises nonresorbable material and/or electrically conductive material.

32. The growth framework as claimed in one of the preceding claims, wherein it can be separated from the tissue which has grown from the biological cells on the framework.

33. The growth framework as claimed in one of the preceding claims, wherein a depot of a pharmacologically active substance can be placed on and/or in the growth framework and/or the tissue.

34. The growth framework as claimed in claim 33, wherein, after transplantation of the tissue into or onto a body, the pharmacologically active substance can be released thereto.

35. The growth framework as claimed in one of the preceding claims, wherein the biologically active stimulus comprises mechanical, electrical, magnetic, chemical, olfactory, acoustic and/or optical stimuli.

36. The growth framework as claimed in one of the preceding claims, wherein the biologically active stimulus comprises stimuli which can be changed in terms of their timing, in particular discontinuous stimulating impulses and/or periodic stimuli.

37. The growth framework as claimed in one of the preceding claims, comprising a means for stimulus generation, in particular a piezoelectric material.

38. A device for producing biological tissue, in particular for transplantation into or onto a human or animal body, and in particular for use of the method as claimed in one of the preceding method claims, said device comprising

a growth chamber,

a growth framework, in particular as claimed in one of claims 21 through 37, arranged in the growth chamber, biological cells arranged on the growth framework, and

a means for generating biologically active stimuli and for exerting the stimuli on the growth framework and/or the biological cells.

39. The device as claimed in claim 38, wherein the stimuli correspond to or are similar to stimuli to which the tissue is naturally exposed in or on the body.

40. The device as claimed in claim 38 or 39, wherein a pharmacologically active substance, preferably a growth-promoting substance, particularly preferably a bone morphogenetic protein, a fibrogen and/or a genetically modified substance can be added.

41. The device as claimed in one of the preceding claims, having a means for generating mechanical, electrical, magnetic, chemical, olfactory, acoustic and/or optical stimuli.

42. The device as claimed in one of the preceding claims, having a means for generating stimuli which can be changed in terms of their timing, in particular stimulating impulses and/or periodic stimuli.

43. The device as claimed in one of the preceding claims, having a means for generating biologically active stimuli, in particular mechanical and/or electrical stimuli, using the piezoelectric effect.

44. A biological tissue which can be produced or is produced by the method as claimed in one of claims 1 through 20, can be produced or is produced with the growth framework as claimed in one of claims 21 through 37, and/or can be produced or is produced in the device as claimed in one of claims 38 through 43, said tissue being cultivated and having a predetermined form, structure and/or functionality.

45. An implant or onplant for implanting or onplanting in or on a human or animal body, comprising the tissue as claimed in claim 44.

46. The implant or onplant as claimed in claim 45, in which said tissue further comprises an active substance depot for releasing a pharmacologically active substance into or onto the body.

47. A bone which can be produced or is produced by the method as claimed in one of claims 1 through 20, can be produced or is produced with the growth framework as claimed in one of claims 21 through 37, and/or can be produced or is produced in the device as claimed in one of claims 38 through 43, said bone having a trabecular and/or cortical structure.

48. The use of the method as claimed in one of claims 1 through 20, of the growth framework as claimed in one of claims 21 through 37, or of the device as claimed in one of claims 38 through 43, for producing or cultivating bone marrow in a bone outside or inside a living body.