Electroactive materials for stimulation of biological activity of bone marrow stromal cells

• US 6,190,893 B1
• Filed: 09/18/1998
• Issued: 02/20/2001
• Est. Priority Date: 09/18/1998
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Martin, Ivan, Rahman, Nahid, Shastri, Venkatram R., Langer, Robert S. Jr.
• Primary Examiner(s): Weber, Jon P.
• Application Number:
  US09/156,317
• Time in Patent Office: 886 Days
• Field of Search: 435/173.8
• US Class Current: 435/173.8
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

Compositions, methods and systems are provided for the stimulation of biological activities within bone marrow stromal cells by applying electromagnetic stimulation to an electroactive material, wherein the electromagnetic stimulation is coupled to the electromagnetic material. In general the present invention involves attaching or associating the desired bone marrow stromal cells to or with a surface comprising an electroactive material, and applying electromagnetic radiation directly to the desired area. In preferred embodiments, the stimulation of biological activities within bone marrow stromal cells results from inducing one or more activities including, but not limited to, gene expression, cell growth, cell differentiation, signal transduction, membrane permeability, cell division and cell signalling. In particularly preferred embodiments, the present invention stimulates bone cell regeneration. In exemplary embodiments, the electroactive materials used in the present invention are either two-dimensional substrates such as thin films having at least one surface of an electroactive material, or in alternative embodiments, the electroactive materials are three-dimensional substrates comprising a matrix having at least one surface of an electroactive material.

Claims

1. A method for stimulating one or more biological activities within cells comprising:

directly contacting bone marrow stromal cells with an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive material, and wherein said electroactive material has attached thereto, or associated therewith, tissue comprising one or more mammalian cells; and

applying electromagnetic stimulation at the location of the electroactive substrate, wherein said electromagnetic stimulation is coupled to said electromagnetic material.

2. The method of claim 1, wherein said stimulation of one or more biological activities results from an alteration in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

3. The method of claim 2, wherein said stimulation of one or more biological activities is selected from the group consisting of gene expression, cell growth, cell differentiation, cell death, cell signalling, cell signal transduction, and any combination of these biological activities.

4. The method of claim 1, wherein said electromagnetic stimulation is coupled to said electromagnetic material by physical contact.

5. The method of claim 1, wherein said electromagnetic stimulation is coupled to said electromagnetic material by electromagnetic induction.

6. The method of claim 1, wherein said electroactive substrate is two-dimensional.

7. The method of claim 6, wherein said electroactive substrate comprises one or more thin films of said electroactive material.

8. The method of claim 1, wherein said electroactive substrate is three-dimensional.

9. The method of claim 8, wherein said electroactive substrate comprises an electroactive material associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, and celluar solids.

10. The method of claim 1, wherein said electroactive material is an electroactive polymer.

11. The method of claim 10, wherein said polymer is conductive.

12. The method of claim 10, wherein said polymer is a semiconductor.

13. The method of claim 10, wherein said polymer is an ionically conducting polymer.

14. The method of claim 10, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyrin), and poly(heme).

15. A method for stimulating one or more biological activities within a cell, comprising:

providing a composition of bone marrow stromal cells and an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive material, and wherein said cells are attached directly thereto;

applying electromagnetic stimulation to said composition, wherein said electromagnetic stimulation is coupled to said electroactive material; and

contacting said composition with a mammalian tissue, wherein the step of contacting may be performed before or after the step of applying.

16. The method of claim 15, wherein said stimulation of one or more biological activities results from an alteration in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

17. The method of claim 16, wherein said stimulation of one or more biological activities is selected from the group consisting of gene expression, cell growth, cell differentiation, cell signal transduction, cell signalling, and any combination of these biological activities.

18. The method of claim 15, wherein said electromagnetic stimulation is coupled to said electromagnetic material by physical contact.

19. The method of claim 15, wherein said electromagnetic stimulation is coupled to said electromagnetic material by electromagnetic induction.

20. The method of claim 15, wherein said electroactive substrate is two-dimensional.

21. The method of claim 20, wherein said electroactive substrate comprises one or more thin films of said electroactive material.

22. The method of claim 15, wherein said electroactive substrate is three-dimensional.

23. The method of claim 22, wherein said electroactive substrate comprises an electroactive material associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, and cellular solids.

24. The method of claim 15;

wherein said electroactive material is an electroactive polymer.

25. The method of claim 24, wherein said polymer is conductive.

26. The method of claim 24, wherein said polymer is a semiconductor.

27. The method of claim 24, wherein said polymer is an ionically conducting polymer.

28. The method of claim 24, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyrin), and poly(heme).

29. A method for stimulating one or more biological activities within a cell, comprising:

providing a composition of bone marrow stromal cells and an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive material, and wherein said cells are attached directly thereto;

applying electromagnetic stimulation to said composition, wherein said electromagnetic stimulation is coupled to said electroactive material;

removing said stimulated cells from said electromagnetic material; and

contacting the stimulated cells with a mammalian tissue, wherein the step of contacting may be performed before or after the step of applying or after the step of removing.

30. The method of claim 29, wherein said stimulation of one or more biological activities results from an alteration in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

31. The method of claim 30, wherein said stimulation of one or more biological activities is selected from the group consisting of gene expression, cell growth, cell differentiation, cell signal transduction, cell signalling, and any combination of these biological activities.

32. The method of claim 29, wherein said electromagnetic stimulation is coupled to said electromagnetic material by physical contact.

33. The method of claim 29, wherein said electromagnetic stimulation is coupled to said electromagnetic material by electromagnetic induction.

34. The method of claim 29, wherein said electroactive substrate is two-dimensional.

35. The method of claim 34, wherein said electroactive substrate comprises one or more thin films of said electroactive material.

36. The method of claim 29, wherein said electroactive substrate is three-dimensional.

37. The method of claim 36, wherein said electroactive substrate comprises an electroactive material associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, and cellular solids.

38. The method of claim 29;

wherein said electroactive material is an electroactive polymer.

39. The method of claim 38, wherein said polymer is conductive.

40. The method of claim 38, wherein said polymer is a semiconductor.

41. The method of claim 38, wherein said polymer is an ionically conducting polymer.

42. The method of claim 38, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyrin), and poly(heme).

43. A method for stimulating one or more biological activities within a cell, comprising;

providing a composition of bone marrow stromal cells and an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive material, and wherein said cells are attached directly thereto;

contacting said composition with mammalian tissue; and

applying electromagnetic stimulation to said composition, wherein said electromagnetic stimulation is coupled to said electroactive material.

44. The method of claim 43, wherein said stimulation of one or more biological activities results from an alteration in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

45. The method of claim 44, wherein said stimulation in one or more biological activities is selected from the group consisting of gene expression, cell growth, cell signal transduction, cell differentiation, cell signalling, cell death and any combination of these biological activities.

46. The method of claim 43, wherein said electromagnetic stimulation is coupled to said electromagnetic material by physical contact.

47. The method of claim 43, wherein said electromagnetic stimulation is coupled to said electromagnetic material by electromagnetic induction.

48. The method of claim 43, wherein said electroactive substrate is two-dimensional.

49. The method of claim 48, wherein said electroactive substrate comprises one or more thin films of said electroactive material.

50. The method of claim 43, wherein said electroactive substrate is three-dimensional.

51. The method of claim 50, wherein said electroactive substrate comprises an electroactive material associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, and cellular solids.

52. The method of claim 43, wherein said electroactive material is in electroactive polymer.

53. The method of claim 52, wherein said polymer is conductive.

54. The method of claim 52, wherein said polymer is a semiconductor.

55. The method of claim 52, wherein said polymer is an ionically conducting polymer.

56. The method of claim 52, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyrin), and poly(heme).

57. A system for stimulating one or more biological activities of cells, comprising:

a composition comprising an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive material, and wherein said electroactive material has attached directly thereto bone marrow stromal cells; and

an apparatus for applying electromagnetic energy at the desired location.

58. The system of claim 57, wherein said electroactive substrate is two-dimensional.

59. The system of claim 57, wherein said electroactive substrate is three-dimensional.