Methods and devices for repair of severed peripheral nerves with erythropoietin

1. An implantable drug-delivery device for repairing a severed peripheral nerve, the drug-delivery device comprising a matrix formed of a biopolymer and an erythropoietin (EPO) entrapped in the matrix, wherein, after in vivo implantation of the drug-delivery device, the EPO elutes over 1 day to 12 weeks and the EPO elutes in a biphasic manner.

2. The implantable drug-delivery device of claim 1 , wherein the matrix is a porous de-cellularized biopolymer matrix of a mammalian peripheral nerve.

3. The implantable drug-delivery device of claim 1 , wherein the matrix is semipermeable and the biopolymer is chitosan, alginic acid, cellulose, elastin, fibrin, a glycosaminoglycan, gelatin, a collagen, or a mixture thereof.

4. The implantable drug-delivery device of claim 3 , wherein the biopolymer is collagen type I, type II, or type III.

5. The implantable drug-delivery device of claim 4 , wherein the biopolymer is type I collagen.

6. The implantable drug-delivery device of claim 5 , wherein the EPO elutes over 1 to 7 days.

7. The implantable drug-delivery device of claim 5 , wherein the EPO elutes over 1 to 3 weeks.

8. The implantable drug-delivery device of claim 5 , wherein the EPO elutes over 3 to 6 weeks.

9. The implantable drug-delivery device of claim 5 , wherein the EPO elutes over 6 to 12 weeks.

10. The implantable drug-delivery device of claim 1 , wherein the device is in the form of a tube, a tubular wrapping cuff, a sheet, a rod, a strip, or a sponge.

11. A method for repairing a severed peripheral nerve having a proximal stump and a distal stump, the method comprising:

providing an implantable drug-delivery device that includes a matrix formed of a biopolymer and an erythropoietin (EPO) entrapped in the matrix,

inserting the proximal stump and the distal stump into a nerve guide implant and stabilizing the nerve stumps with a suture, and

implanting the drug-delivery device at the site of the severed nerve, wherein, after implantation in vivo of the drug-delivery device, the EPO elutes over 1 day to 12 weeks and the EPO elutes in a biphasic manner.

12. The method of claim 11 , wherein the matrix is a porous de-cellularized biopolymer matrix of a mammalian peripheral nerve and the implantable drug-delivery device is placed inside of the nerve guide implant prior to inserting the proximal stump and the distal stump.

13. The method of claim 11 , wherein the matrix is semipermeable and the biopolymer is chitosan, alginic acid, cellulose, elastin, fibrin, a glycosaminoglycan, gelatin, a collagen, or a mixture thereof.

14. The method of claim 13 , wherein the biopolymer is collagen type I, type II, or type III.

15. The method of claim 14 , wherein the biopolymer is type I collagen.

16. The method of claim 15 , wherein the EPO elutes over 1 to 7 days.

17. The method of claim 15 , wherein the EPO elutes over 1 to 3 weeks.

18. The method of claim 15 , wherein the EPO elutes over 3 to 6 weeks.

19. The method of claim 15 , wherein the EPO elutes over 6 to 12 weeks.

20. The method of claim 11 , wherein the device is in the form of a tube, a tubular wrapping cuff, a sheet, a rod, a strip, or a sponge.

21. The method of claim 20 , wherein the drug-delivery device is affixed to an outer surface of the nerve guide implant.

22. The method of claim 20 , wherein the drug-delivery device is affixed to an inner surface of the nerve guide implant prior to the attaching step.

23. The method of claim 11 , wherein a gap between the proximal stump and the distal stump is 1 cm or less and the EPO elutes over 1 to 7 days.

24. The method of claim 11 , wherein a gap between the proximal stump and the distal stump is 1 cm to 3 cm and the EPO elutes over 1 to 6 weeks.

25. The method of claim 11 , wherein a gap between the proximal stump and the distal stump is 3 cm to 10 cm and the EPO elutes over 6 to 12 weeks.