Electrically-charged nerve guidance channels

• US 5,030,225 A
• Filed: 11/30/1990
• Issued: 07/09/1991
• Est. Priority Date: 03/13/1987
• Status: Expired due to Fees

• Current Assignee: Brown University
• Original Assignee: Brown University
• Inventors: Aebischer, Patrick, Valentini, Robert F.
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): Jackson, Gary
• Application Number:
  US07/621,081
• Time in Patent Office: 221 Days
• Field of Search: 606/152, 623/12, 623/24, 623/25
• US Class Current: 606/152
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 17/1128 of nerves
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable, resorptive for implantable prostheses A61F2210/0004
• CPC Class Codes: A61F 2002/30235 tubular, e.g. sleeves
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 31/04 Macromolecular materials
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61N 1/0556 Cuff electrodes
• CPC Class Codes: A61N 1/36103 Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
• CPC Class Codes: C08L 27/16 Homopolymers or copolymers or vinylidene fluoride
• CPC Class Codes: Y10S 977/908 Mechanical repair performed/surgical

Abstract

A medical device is disclosed for use in regenerating a severed nerve. The device includes an implantable, tubular, electrically-charged membrane having openings adapted to receive the ends of the severed nerve and a lumen having a diameter ranging from about 0.5 millimeters to about 2.0 centimeters to permit regeneration of the nerve therethrough. The membrane is fabricated such that an electric charge is exhibited at the inner membrane surface to stimulate regeneration by axonal sprouting and process extension. Also disclosed are methods for repairing a severed nerve and for preparing a medical device for use in regeneration of a severed nerve.

Claims

1. A medical device for use in regenerating a severed nerve, the device comprising an implantable, tubular, electrically-charged membrane having openings adapted to receive the ends of said severed nerve and a lumen having a diameter ranging from about 0.5 millimeters to about 2.0 centimeters to permit regeneration of the nerve therethrough, said membrane being fabricated such that an electrical charge is exhibited at the inner surface of said membrane to stimulate regeneration by axonal sprouting and process extension.

2. The device of claim 1 wherein said membrane comprises a polymeric material.

3. The device of claim 1 wherein said membrane has an average charge density of about 1 to 100 nanoColoumbs/cm².

4. The device of claim 3 wherein said electret material is polarized such that a positive charge is generated at said inner membrane surface.

5. The device of claim 3 wherein said electret material is polarized such that a negative charge is generated at said inner membrane surface.

6. The device of claim 1 wherein the thickness of the membrane ranges from about 0.05 to about 1.0 millimeter.

7. The device of claim 1 wherein the membrane is permeable to solutes having a molecular weight of about 100,000 daltons or less.

8. The device of claim 1 wherein the membrane is impermeable to fibroblasts and other scar-forming connective tissue cells.

9. The device of claim 1 wherein said membrane comprises an electret material.

10. The device of claim 9 wherein said surface charge of said material is persistent.

11. The device of claim 10 wherein said electret material is selected from the group consisting of polytetrafluoroethylene (PTFE), polylvinylchloride, polyethylene, polylamides, polymethyl methacrylate, polypropylene, polylethylene terapthalate, and mixtures thereof.

12. The device of claim 11 wherein said electret material comprises polytetrafluoroethylene.

13. The device of claim 9 wherein said surface charge of said material is transient.

14. The device of claim 13 wherein said membrane comprises a piezoelectric material.

15. The device of claim 14 wherein said piezoelectric material has a polarization constant ranging from about 0.5 to about 35 picoColoumbs per Newton.

16. The device of claim 15 wherein said piezoelectric material has a polarization constant ranging from about 1 to about 20 picoColoumbs per Newton.

17. The device of claim 14 wherein said piezoelectric material comprises a material selected from the group of polyvinylidene fluoride, polyvinyl fluoride, polyvinyl chloride, collagen, nylon 11, polyhydroxybutyrate, poly-γ

-benzyl-glutamate, poly-γ

-methyl-glutamate, copolymers of trifluoroethylene and such polymers, and derivatives of such polymers.

18. The device of claim 17 wherein said piezoelectric material comprises polyvinylidene fluoride.

19. The device of claim 18 wherein said polyvinylidene fluoride material has a chain length of about 2,000 to about 15,000 repeat units.

20. The device of claim 18 wherein said polyvinylidene fluoride material has an orthorhombic unit cell structure containing two chains with the same orientation and, consequently, a permanent dipole moment.

21. The device of claim 20 wherein said piezoelectric material comprises polyvinylidene fluoride exhibiting an alignment of the permanent dipoles and a polarization constant of about 1 to about 20 picoColoumbs per Newton.

22. A method for repairing a severed nerve, said comprising:

providing a protective medical device including an implantable, tubular, biocompatible, electrically-charged membrane, said membrane having opening adapted to receive the ends of a severed nerve and a lumen having a diameter ranging from about 0.5 millimeters to about 2.0 centimeters to permit regeneration of the nerve therethrough, said electrically-charged membrane being fabricated such that an electrical charge is exhibited at the inner surface of said membrane to stimulate axonal sprouting and process extension;

placing said severed nerve ends in proximity to each other within said lumen; and

securing said nerve ends to said device.

23. The method of claim 22 wherein the step of securing said nerve ends further comprises suturing said nerve ends to said membrane.

24. The method of claim 23 wherein the step of securing said nerve ends further comprises securing said nerve ends with an adhesive.

25. The method of claim 23 wherein said nerve ends are secured by friction.

26. The method of claim 22 further comprising the steps of:

splitting said tubular membrane along a line of weakness; and

removing said split tube from said nerve ends after said nerve ends have joined.

27. The method of claim 22 wherein said method further comprises the step of filling said lumen with saline before said placing step.

28. The method of claim 27 wherein said filling step comprises filling said lumen with a matrix material selected from the group of laminin, collagen, and glycosaminoglycan.

29. The method of claim 27 wherein said filling step comprises seeding said lumen with a nerve growth factor.

30. The method of claim 27 wherein said filling step comprises seeding said lumen with Schwann cells.

31. The method of claim 22 wherein said method further comprises, after the securing step, the step of allowing said device to undergo biodegradation in vivo.

32. The method of claim 22 wherein said providing step comprises providing a membrane having an average charge density of about 1 to 100 nanoColoumbs/cm².

33. The method of claim 22 wherein said providing step comprises providing a membrane that is permeable to solutes having a molecular weight of about 100,000 daltons or less.

34. The method of claim 22 wherein said providing step comprises providing a membrane that is impermeable to fibroblasts and other scar-forming connective tissue cells.

35. The method of claim 22 wherein said providing step comprises providing a membrane having a thickness ranging from about 0.05 to about 1.0 millimeter.

36. The method of claim 22 wherein said providing step comprises providing a membrane including an electret material.

37. The method of claim 36 wherein said providing step comprises providing a membrane including a positively poled electret material.

38. The method of claim 36 wherein said providing step comprises providing a membrane including a negatively poled electret material.

39. The method of claim 36 wherein said providing step comprises providing a membrane including an electret material having a persistent surface charge.

40. The method of claim 36 wherein said providing step comprises providing a membrane including an electret material selected from the group consisting of polytetrafluoroethylene (PTFE), polylvinylchloride, polyethylene, polylamides, polymethyl methacrylate, polypropylene, polylethylene terapthalate, and mixtures thereof.

41. The method of claim 40 wherein said providing step comprises providing a membrane including polytetrafluoroethylene.

42. The method of claim 36 wherein said providing step comprises providing a membrane including an electret material with a transient charge.

43. The method of claim 42 wherein said providing step comprises providing a membrane including a piezoelectric material.

44. The method of claim 43 wherein said providing step comprises providing a membrane including a piezoelectric material having a polarization constant ranging from about 0.5 to about 35 picoColoumbs per Newton.

45. The method of claim 44 wherein said providing step comprises providing a membrane including a piezoelectric material having a polarization constant ranging from about 1 to about 20 picoColoumbs per Newton.

46. The method of claim 43 wherein said providing step comprises providing a membrane including a piezoelectric material selected from the group of polyvinylidene fluoride, polyvinyl fluoride, polyvinyl chloride, collagen, nylon 11, polyhydroxybutyrate, poly-γ

-benzyl-glutamate, poly-γ

-methyl-glutamate, copolymers of trifluoroethylene and such polymers, and derivatives of such polymers.

47. The method of claim 46 wherein said providing step comprises providing a membrane including polyvinylidene fluoride.

48. The method of claim 47 wherein said providing step comprises providing a membrane including polyvinylidene fluoride having a chain length of about 2,000 to about 15,000 repeat units.

49. The method of claim 47 wherein said providing step comprises providing a membrane including polyvinylidene fluoride exhibiting an orthorhombic unit cell structure containing two chains with the same orientation and, consequently, a permanent dipole moment.

50. The method of claim 49 wherein said providing step comprises providing a membrane including polyvinylidene fluoride exhibiting an alignment of the permanent dipoles and a polarization constant of about 1 to about 20 picoColoumbs per Newton.