Conduit for peripheral nerve replacement

• US 9,675,358 B2
• Filed: 03/15/2013
• Issued: 06/13/2017
• Est. Priority Date: 04/12/2012
• Status: Active Grant

• Current Assignee: Nuvotronics LLC, Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Argenta, Louis C., Morykwas, Michael J., Rosenbalm, Tabitha, Wagner, William D., Levi, Nicole
• Primary Examiner(s): Woo, Julian W
• Application Number:
  US14/391,346
• Publication Number:
  US 20150032137A1
• Time in Patent Office: 1,551 Days
• CPC Class Codes: A61B 17/1128 of nerves
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable or resorptive
• CPC Class Codes: A61B 2017/00831 Material properties
• CPC Class Codes: A61B 2017/00991 Telescopic means
• CPC Class Codes: A61B 2017/1132 End-to-end connections
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/446 with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08G 63/12 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08G 63/47 by unsaturated monocarboxylic acids or unsaturated monohydric alcohols or reactive derivatives thereof
• CPC Class Codes: C08L 67/00 Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: H01B 1/125 comprising aliphatic main chains, e.g. polyactylenes

Abstract

A biphasic material and devices comprising the same are provided for the development of conductive conduits that may be used for the treatment of peripheral nerve injury. These devices or conduits are designed such that repeated electric field gradients can be initiated to promote neurite and axonal outgrowth. Conducting conduits using doped synthetic and/or natural polymers create specifically patterned high and low conducting segmented materials, which are mechanically used to produce the electrical properties needed for nerve conduits. These electrical properties stimulate neurite outgrowth and axonal repair following a peripheral nerve transection.

Claims

1. A biphasic material, comprising at least two first segments and at least two second segments, the first segments comprising a doped conductive polymer having a first polymer component doped with a non-metal component which increases the conductivity of the first polymer component, and the second segments comprising a second conductive polymer component, wherein the at least two first segments are disposed in contact with the at least two second segments, in alternating fashion, to provide the biphasic material with repeating alternating first and second polymer components.

2. The biphasic material of claim 1, wherein the first polymer component comprises a bioabsorbable polymer.

3. The biphasic material of claim 1, wherein the first polymer component comprises poly glycerol sebacate, an esterified polyglycerol sebacate, glycolic acid, polydiolcitrate, poly(ester-urethane)urea, polycaprolactone, hydroxyapatite, hyaluronic acid, alginate, collagen, elastin, vimentin, laminin, fibrin, melanin, gum arabic, polycaprolactonefumarate, poly(octane diol) citrate, lactic acid, or combinations thereof.

4. The biphasic material of claim 3, wherein the esterified polyglycerol sebacate is acrylated polyglycerol sebacate.

5. The biphasic material of claim 1, wherein the second polymer component comprises a bioabsorbable polymer.

6. The biphasic material of claim 1, wherein the second polymer component comprises poly glycerol sebacate, an esterified polyglycerol sebacate, glycolic acid, polydiolcitrate, poly(ester-urethane)urea, polycaprolactone, hydroxyapatite, alginate, hyaluronic acid, collagen, elastin, vimentin, laminin, fibrin, melanin, gum arabic, polycaprolactonefumarate, poly(octane diol) citrate, lactic acid, or combinations thereof.

7. The biphasic material of claim 6, wherein the esterified polyglycerol sebacate is acrylated polyglycerol sebacate.

8. The biphasic material of claim 1, wherein the non-metal component comprises polypyrrole, polyaniline, poly(3,4-ethylenedioxythiophene), polyacetylene carbon nanotubes, a silicate, or combinations thereof.

9. The biphasic material of claim 1, wherein the non-metal component has a conductivity in the range of 5-200 S/cm.

10. The biphasic material of claim 1, wherein the first polymer component and second polymer component are configured to support differing electric field gradients, respectively, therein.

11. The biphasic material of claim 1, wherein the doped conductive polymer has a conductivity of 10⁻

6-10<sup>−

4</sup> S/cm.

12. The biphasic material of claim 1, wherein the second polymer component has a conductivity less than 1.25×

10<sup>−

5</sup> S/cm.

13. The biphasic material of claim 1, wherein the first segments have the mechanical properties of native human nerve tissue.

14. The biphasic material of claim 13, wherein the first polymer has one or more of an elastic modulus of 0.4-0.7 mPa and a tensile strength of 0.21-1.49 N.

15. The biphasic material of claim 13, wherein the second segments have the mechanical properties of native human nerve tissue.

16. The biphasic material of claim 15, wherein the second polymer has one or more of an elastic modulus of 0.4-0.7 mPa and a tensile strength of 0.21-1.49 N.

17. A method of repairing a damaged nerve, comprising:

a. providing a tube having a hollow lumen with opposing proximal and distal open ends, the tube comprising the biphasic material of claim 1, wherein the tube is configured to support a plurality of electric field gradients along its length and permit the ingrowth of nerve tissue within the lumen; and

b. securing a proximal stump of the damaged nerve within the proximal end of the tube and, securing a distal stump of the damaged nerve within the distal end of the tube such that proximal and distal stump of the damaged nerve are in electrical communication with the tube.

18. The method according to claim 17, further comprising seeding the tube with one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

19. The biphasic material according to claim 1, comprising one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

20. The biphasic material of claim 1, wherein the first polymer component is acrylated polyglycerol sebacate, the second polymer component is acrylated polyglycerol sebacate, and the non-metal component is polypyrrole.

49. A sheet comprising the biphasic material of claim 1.

50. The sheet of claim 49, comprising one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

51. A strip comprising the biphasic material of claim 1.

52. The strip of claim 51, comprising one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

21. An open-ended, hollow tube configured to support a plurality of electric field gradients along its length and having a lumen extending therethrough to permit the growth of nerve tissue therein, the tube comprising a plurality of first conductive tubular segments and a plurality of second conductive tubular segments adjoined along a common axis of the tube to provide the lumen along the common axis, the first conductive tubular segments comprising a first polymer component doped with a non-metal component which increases the conductivity of the first polymer component, and the second tubular segments comprising a second conductive polymer component.

22. The tube according to claim 21, wherein the tube is bioresorbable.

23. The tube according to claim 21, wherein the first polymer component comprises a bioabsorbable polymer.

24. The tube according to claim 21, wherein the first polymer component comprises poly glycerol sebacate, an esterified polyglycerol sebacate, glycolic acid, polydiolcitrate, poly(ester-urethane)urea, polycaprolactone, hydroxyapatite, alginate, collagen, elastin, vimentin, laminin, fibrin, melanin, hyaluronic acid, gum arabic, polycaprolactonefumarate, poly(octane diol) citrate, lactic acid, or combinations thereof.

25. The tube according to claim 24, wherein the esterified polyglycerol sebacate is acrylated polyglycerol sebacate.

26. The tube according to claim 21, wherein the second polymer component comprises a bioabsorbable polymer.

27. The tube according to claim 21, wherein the second polymer component comprises poly glycerol sebacate, an esterified polyglycerol sebacate, glycolic acid, polydiolcitrate, poly(ester-urethane)urea, polycaprolactone, hydroxyapatite, alginate, collagen, elastin, vimentin, laminin, hyaluronic acid, fibrin, melanin, gum arabic, polycaprolactonefumarate, poly(octane diol) citrate, lactic acid, or combinations thereof.

28. The tube according to claim 27, wherein the esterified polyglycerol sebacate is acrylated polyglycerol sebacate.

29. The tube according to claim 21, wherein the non-metal component comprises polypyrrole, polyaniline, poly(3,4-ethylenedioxythiophene), polyacetylene carbon nanotubes, a silicate, or combinations thereof.

30. The tube according to claim 21, wherein the non-metal component has a conductivity in the range of 5-200 S/cm.

31. The tube according to claim 21, wherein the second polymer components has a relatively lower conductivity than the first polymer component.

32. The tube according to claim 21, wherein the doped conductive polymer has a conductivity of 10⁻

6-10<sup>−

4</sup> S/cm.

33. The tube according to claim 21, wherein the second polymer component has a conductivity less than 1.25×

10<sup>−

5</sup> S/cm.

34. The tube according to claim 21, wherein the first tubular segments have the mechanical properties of native human nerve tissue.

35. The tube according to claim 34, wherein the first polymer has one or more of an elastic modulus of 0.4-0.7 mPa and a tensile strength of 0.21-1.49 N.

36. The tube according claim 34, wherein the second tubular segments have the mechanical properties of native human nerve tissue.

37. The tube according to claim 36, wherein the second polymer has one or more of an elastic modulus of 0.4-0.7 mPa and a tensile strength of 0.21-1.49 N.

38. The tube according to claim 21, wherein the length of each of the first tubular segments and the length of each of the second tubular segments are equal.

39. The tube according to claim 21, wherein the length of each of the first tubular segments and the length of each of the second tubular segments are not equal.

40. The tube according to claim 39, wherein the length of the first tubular segments is 10-1200 μ

m.

41. The tube according to claim 40, wherein the length of the first tubular segments is at least about 600 μ

m.

42. The tube according to claim 39, wherein the length of the second tubular segments are less than the first tubular segments.

43. The tube according to claim 39, wherein the length of the second tubular segments is 10-600 μ

m.

44. The tube according to claim 21, wherein the cylinder wall thickness of the plurality of first tubular segments is 0.1 mm to 1.0 cm.

45. The tube according to claim 21, wherein the cylinder wall thickness of the plurality of second tubular segments is 0.1 mm to 1.0 cm.

46. The tube according to claim 21, wherein each successive adjoined tubular segment has a smaller radius than a preceding tubular segment.

47. The tube of claim 46, wherein each tubular segment of the plurality of tubular segments has a cylinder wall thickness of 0.1 mm to 1.0 cm.

48. The tube according to claim 46, comprising one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

53. The tube according to claim 21, wherein at least one of the first and second polymer components comprises an esterified polyglycerol sebacate polymer, the repeating structural unit of the esterified polyglycerol sebacate polymer having the formula

54. The tube according to claim 53, wherein the repeating structural unit of the esterified polyglycerol sebacate polymer has the formula

55. The tube according to claim 21, comprising one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

56. The tube of claim 21, wherein the first conductive polymer component is acrylated polyglycerol sebacate, the second conductive polymer component is acrylated polyglycerol sebacate, and the non-metal component is polypyrrole.

57. A method of making a tube configured to support a plurality of electric field gradients along its length, comprising:

a. providing a mold having a plurality of annular valleys disposed on an exterior surface of the mold in spaced apart relation along a longitudinal axis thereof;

b. placing a first conductive polymer in the valleys;

c. placing a high conductivity polymer over the first conductivity polymer, the high conductivity polymer having a greater conductivity than that of the first conductive polymer;

d. adhering the first conductive polymer and high conductivity polymer to one another; and

e. removing the adhered first conductive polymer and high conductivity polymer from the mold to provide the tube configured to support a plurality of electric field gradients along its length.

58. The method according to claim 57, wherein at least one of the first conductive polymer and high conductivity polymer comprise a bioabsorbable material.

59. The method according to claim 57, wherein adhering the polymers comprises crosslinking the first conductive polymer and high conductivity polymer.

60. The method according to claim 57, wherein providing a mold comprises providing a cylindrical mold.

61. The method according to claim 57, further comprising forming pores within the first conductive polymer and high conductivity polymer.

62. The method according to claim 57, further comprising seeding the tube with one or more of Schwann cells, neuronal cells, stem cells, and fibroblasts.

63. The method of claim 57, wherein the low conductivity polymer component comprises acrylated polyglycerol sebacate and the high conductivity polymer component comprises acrylated polyglycerol sebacate and polypyrrole.