Neuronal stimulation using electrically conducting polymers

• US 6,095,148 A
• Filed: 11/03/1995
• Issued: 08/01/2000
• Est. Priority Date: 11/03/1995
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Inventors: Schmidt, Christine E., Langer, Robert S., Vacanti, Joseph P., Shastri, Venkatram R.
• Primary Examiner(s): Dvorak, Linda C. M.
• Assistant Examiner(s): ROLLINS, ROSILAND STACIE
• Application Number:
  US08/552,761
• Time in Patent Office: 1,733 Days
• Field of Search: 607/50, 607/115, 607/116, 607/117, 607/118, 128/898
• US Class Current: 128/898
• CPC Class Codes: A61B 17/11 for performing anastomosis; Buttons for anastomosis
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C08L 45/00 Compositions of homopolymers or copolymers of compounds having no unsaturated aliphatic radicals in side chain, and having one or more carbon-to-carbon double bonds in a carbocyclic or in a heterocyclic ring system; Compositions of derivatives of such polymers of cyclic anhydrides or imides C08L35/00; of cyclic esters of polyfunctional acids C08L31/00
• CPC Class Codes: C08L 79/02 Polyamines
• CPC Class Codes: C08L 81/00 Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing sulfur with or without nitrogen, oxygen or carbon only; Compositions of polysulfones; Compositions of derivatives of such polymers
• CPC Class Codes: C12M 25/08 electrically charged
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12M 35/08 Chemical, biochemical or biological means, e.g. plasma jet, co-culture
• 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 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

Methods and support systems are provided for modifying the regeneration, differentiation, or function of cells. In one embodiment, electrically conducting biocompatible polymers may be used alone or in combination with a polymeric support for in vitro nerve cell regeneration, or in vivo to aid in healing nervous tissue defects. The conductive polymers may implanted adjacent to or seeded with nerve cells. Voltage or current is applied to the polymer in a range which induces the desired effect on the cells while not damaging the cells. The methods and systems can be used in a variety of applications to enhance in vivo or in vitro growth or regeneration of nervous tissue.

Claims

1. A method for altering the regeneration, differentiation or differentiated cell function of cells comprising:

attaching or abutting cells to a surface comprising an electrically conducting polymer for a sufficient time to alter the regeneration, differentiation or differentiated cell function of the cells attached to or abutting the polymer, without damaging the cells,

wherein the cells are selected from the group consisting of endothelial cells, parenchymal cells, cells forming bone or cartilage, and neurons.

2. The method of claim 1, wherein the cells are neurons.

3. The method of claim 1, wherein the cells attach to the electrically conducting polymer.

4. The method of claim 1, wherein the method further comprises applying an electric current or voltage to the polymer in an effective amount and for a sufficient time to alter the regeneration, differentiation or differentiated cell function of the cells attached or abutted to the polymer, without damaging the cells.

5. The method of claim 2 wherein the electrically conductive polymer is selected from the group consisting of polyanilines, polypyrroles, polythiophenes, and copolymers and blends thereof.

6. The method of claim 2 wherein the electrically conductive polymer is polypyrrole.

7. The method of claim 2, wherein the neurons are selected from the group consisting of naturally occurring mammalian neurons and recombinant neurons.

8. The method of claim 2, wherein the neurons are selected from the group consisting of brain, spinal, sensory, and motor neurons.

9. The method of claim 2 wherein the polymer is coated onto or blended with a polymeric support structure.

10. The method of claim 9 wherein the structure comprises a biocompatible polymer.

11. The method of claim 10 wherein the structure comprises a biodegradable polymer.

12. The method of claim 2 wherein molecules selected from the group consisting of proteins, antibodies nerve growth factors, hormones and attachment molecules are covalently attached to the electrically conductive polymer.

13. The method of claim 12 further comprising implanting with the polymer a composition which enhances healing of the nervous tissue.

14. The method of claim 2 further comprising implanting the conductive polymer into a patient in need of treatment and applying a voltage or current to the polymer in an amount effective to enhance the regeneration, differentiated cell function, or differentiation of nervous tissue comprising the neurons.

15. The method of claim 13 wherein the nervous tissue is selected from the group consisting of central and peripheral nervous system tissue.

16. The method of claim 13 comprising implanting the polymer into a patient in need of treatment and applying a voltage or current to the polymer in an amount effective to enhance regeneration of the neurons.

17. The method of claim 14 wherein the extension of neurites on the neurons is enhanced.

18. A device for altering the regeneration, differentiation or differentiated cell function of neurons comprising:

a) an electrically conducting polymer in the form of a structure selected from the group consisting of sutures, tubes, sheets, films, and scaffolds for tissue engineering, and

b) first and second electrodes for inducing a voltage or current across the polymer, wherein the first and second electrodes are electrically coupled with the polymer,

wherein the device is configured and arranged to accept said neurons onto said electrically conducting polymer for a sufficient time and is capable of the alteration of regeneration, differentiation, or differentiated cell function of neurons without damaging the cells when the device is attached to or abuts neurons and an effective amount of a voltage or current to alter the regeneration, differentiation or differentiated cell function of the neurons is applied to the neurons for a sufficient time.

19. The device of claim 18 wherein the electrically conductive polymer is selected from the group consisting of polyanilines, polypyrroles, polythiophenes, and copolymers and blends thereof.

20. The device of claim 18 wherein the electrically conductive polymer comprises polypyrrole.

21. The device of claim 18 wherein the device is capable of the alteration of regeneration, differentiation, or differentiated cell function of neurons selected from the group consisting of brain, spinal, sensory and motor neurons.

22. The device of claim 18 wherein the electrically conductive polymer is coated onto or blended with a polymeric support structure.

23. The device of claim 18 wherein the structure comprises a biocompatible polymer.

24. The device of claim 18 wherein the structure comprises a biodegradable polymer.

25. The device of claim 18 further comprising a composition which stimulates neuron growth.

26. The device of claim 18, wherein the electrically conducting polymer is capable of having neurons attach thereto.