DESIGN OF A CONDUIT FOR PERIPHERAL NERVE REPLACEMENT

• US 20150032137A1
• Filed: 03/15/2013
• Published: 01/29/2015
• Est. Priority Date: 04/12/2012
• Status: Active Grant

• Current Assignee: Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Wagner, William D., Argenta, Louis C., Morykwas, Michael J., Levi-Polyachenko, Nicole, Rosenbalm, Tabitha
• Granted Patent: US 9,675,358 B2
• Time in Patent Office: Days
• US Class Current: 606/152
• 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:

a. a first polymer component doped with a non-metal component, which increases the conductivity of the first polymer component, and

b. a second polymer component.

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 is capable of 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 first polymer component has a conductivity of at least about 10⁻

6-10<sup>−

4</sup> S/cm.

12. The biphasic material of claim 1, wherein the second polymer component has a conductivity of at least about 0-1.25×

10<sup>−

5</sup> S/cm.

13. The biphasic material of claim 1, wherein the first polymer component has the mechanical properties of native nerve.

14. The biphasic material of claim 13, wherein the mechanical properties of the first polymer are selected from the group consisting of an elastic modulus of at least about 0.4-0.7 mPa, a tensile strength of at least about 0.21-1.49 N, and a biodegradability of at least about 3-12 months.

15. The biphasic material claim 1, wherein the second polymer component has the mechanical properties of native nerve.

16. The biphasic material of claim 15, wherein the mechanical properties of the second polymer are selected from the group consisting of an elastic modulus of at least about 0.4-0.7 mPa, a tensile strength of at least about 0.21-1.49 N, and a biodegradability of at least about 3-12 months.

42. A telescoping segmented apparatus comprising a plurality of tubular segments disposed along a longitudinal axis, wherein each segment of the plurality of tubular segments comprises the biphasic material of claim 1, and wherein each successive tubular segment has a smaller radius than a preceding tubular segment.

43. The telescoping apparatus of claim 42, wherein each tubular segment of the plurality of tubular segments has a cylinder wall thickness of at least about 0.1 mm to 1.0 cm.

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

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

54. A method of repairing a damaged nerve comprising the steps of:

a. placing a tube comprising the biphasic material of claim 1 at a nerve to be repaired, wherein the tube is configured to support a plurality of electric field gradients along its length; and

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

55. The biphasic material according to claim 1, comprising cells.

57. The telescoping segmented apparatus according to claim 42, comprising cells.

58. The sheet of claim 44, comprising cells.

59. The strip of claim 45, comprising cells.

61. The method according to claim 54, further comprising the step of seeding the tube with cells.

17. A tube configured to support a plurality of electric field gradients along its length, comprising a plurality of first tubular segments and a plurality of second tubular segments adjoined along a common axis of the tube, the first 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 polymer component.

18. The tube according to claim 17, wherein the tube is bioresorbable.

19. The tube according to claim 17, wherein the first polymer component comprises a bioabsorbable polymer.

20. The tube according to claim 17, 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.

21. The tube according to claim 20, wherein the esterified polyglycerol sebacate is acrylated polyglycerol sebacate.

22. The tube according to claim 17, wherein the second polymer component comprises a bioabsorbable polymer.

23. The tube according to claim 17, 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.

24. The tube according to claim 23, wherein the esterified polyglycerol sebacate is acrylated polyglycerol sebacate.

25. The tube according to claim 17, wherein the non-metal component comprises polypyrrole, polyaniline, poly(3,4-ethylenedioxythiophene), polyacetylene carbon nanotubes, a silicate, or combinations thereof.

26. The tube according to claim 17, wherein the non-metal component is capable of conductivity in the range of 5-200 S/cm.

27. The tube according to claim 17, wherein the second polymer components has a relatively lower conductivity than the first polymer component.

28. The tube according to claim 17, wherein the first polymer component has a conductivity of at least about 10⁻

6-10<sup>−

4</sup> S/cm.

29. The tube according to claim 17, wherein the second polymer component has a conductivity of at least about 0-1.25×

10<sup>−

5</sup> S/cm.

30. The tube according to claim 17, wherein the first polymer component has the mechanical properties of native nerve.

31. The tube according to claim 30, wherein the mechanical properties of the first polymer are selected from the group consisting of an elastic modulus of at least about 0.4-0.7 mPa, a tensile strength of at least about 0.21-1.49 N, and a biodegradability of at least about 3-12 months.

32. The tube according claim 17, wherein the second polymer component has the mechanical properties of native nerve.

33. The tube according to claim 32, wherein the mechanical properties of the second polymer are selected from the group consisting of an elastic modulus of at least about 0.4-0.7 mPa, a tensile strength of at least about 0.21-1.49 N, and a biodegradability of at least about 3-12 months.

34. The tube according to claim 17, wherein the length of the first tubular segments and the length of the second tubular segments are equal.

35. The tube according to claim 17, wherein the length of the first tubular segments and the length of the second tubular segments are not equal.

36. The tube according to claim 35, wherein the length of the first tubular segments is at least about 10-1200 μ

m.

37. The tube according to claim 36, wherein the length of the first tubular segments is at least about 600 μ

m.

38. The tube according to claim 35, wherein the length of the second tubular segments are less than the first tubular segments.

39. The tube according to claim 35, wherein the length of the second tubular segments is at least about 10-600 μ

m.

40. The tube according to claim 17, wherein the cylinder wall thickness of the plurality of first tubular segments is at least about 0.1 mm to 1.0 cm.

41. The tube according to claim 17, wherein the cylinder wall thickness of the plurality of second tubular segments is at least about 0.1 mm to 1.0 cm.

56. The tube according to claim 17, comprising cells.

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

a. providing a mold having one or more depressions disposed therein;

b. placing a low conductivity polymer in the depressions;

c. placing a high conductivity polymer over the low conductivity polymer;

d. adhering the low and high conductivity polymers to one another; and

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

47. The method according to claim 46, wherein at least one of the low conductivity polymer and high conductivity polymer comprise a bioabsorbable material.

48. The method according to claim 46, wherein the step of adhering the polymers comprises crosslinking the low and high conductivity polymers.

49. The method according to claim 46, wherein the step of providing a mold comprises providing a cylindrical mold in which the depressions are disposed on a surface of the mold.

50. The method according to claim 46, further comprising the step of forming pores within the low and high conductivity polymers.

51. The method according to claim 46, wherein the depressions comprise grooves.

53. The esterified polyglycerol sebacate polymer of claim 51, the repeating structural unit of the esterified polyglycerol sebacate polymer having the formula

60. The method according to claim 46, further comprising the step of seeding the tube with cells.

52. An esterified polyglycerol sebacate polymer, the repeating structural unit of the esterified polyglycerol sebacate polymer having the formula