IP Library Granted Patent US 9,597,434
Granted Patent B2
US 9,597,434 · App. 14/783,895 · Granted Mar 21, 2017

Surface treatments for vascular stents and methods thereof

Inventors: Matthew Kipper (Fort Collins, CO); Ketul Popat (Fort Collins, CO); Melissa Reynolds (Fort Collins, CO); Victoria Leszczak (Fort Collins, CO); Raimundo Romero (Fort Collins, CO)
Assignee: Colorado State University Research Foundation
A61L31/10A61L31/022A61L31/16B05D7/58C25D11/26A61L2300/114A61L2300/236A61L2300/252A61L2300/414A61L2300/45A61L2300/606A61L2300/61A61L2400/12A61L2400/18A61L2420/02A61L2420/08
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Quick Facts
Patent No.
US 9,597,434
App. No.
14/783,895
Granted
Mar 21, 2017
Kind
B2
Abstract

Surface modified medical devices with nanotubes and polyelectrolyte multilayers, methods of promoting endothelialization, and methods of modifying a medical device surface are disclosed. Nanotubes may be formed on the surface of the medical device and may further be coated with polyelectrolyte multilayers of a polycation and a polyanion. The surface modification is characterized by a nanopattern on the surface of the medical device, with biomimetic properties.

Claims (56)

1. A medical device for promoting endothelialization comprising:

a body having at least a first surface;

a plurality of nanotubes formed on the first surface of the body;

at least one polyelectrolyte layer deposited on the nanotubes comprising: a polycation layer; and

a polyanion layer,

wherein the nanotubes and the polyelectrolyte layers form a nanopatterned structure on the first surface of the body of the medical device to promote endothelialization and reduce platelet adhesion and activation.

2. The medical device of claim 1 , wherein the medical device is a vascular stent.

3. The medical device of claim 1 , wherein at least one of the polycation or polyanion comprises nitric oxide-releasing groups.

4. The medical device of claim 3 , wherein the device releases nitric oxide from the surface.

5. The medical device of claim 4 , wherein the device releases nitric oxide at a rate of about 5 nmol/s to about 500 nmol/s.

6. The medical device of claim 5 , wherein the device releases nitric oxide for a period of at least about 2 to about 3 weeks.

7. The medical device of claim 3 , wherein the polycation comprises nitric oxide-releasing groups.

8. The medical device of claim 3 , wherein the polyanion comprises nitric oxide-releasing groups.

9. The medical device of claim 1 , wherein the nanotubes comprise titanium, a titanium alloy, a titanium oxide, or stainless steel.

10. The medical device of claim 1 , wherein the polycation is chitosan.

11. The medical device of claim 1 , wherein the polyanion is a glycosaminoglycan.

12. The medical device of claim 11 , wherein the glycosaminoglycan is selected from heparin, heparan sulfate, chondroitin sulfate, keratan sulfate, dextran sulfate, a sulfated polysaccharide, and a sulfate-containing polylelectrolyte.

13. The medical device of claim 1 , further comprising a growth factor adsorbed on the at least one polyelectrolyte layer.

14. The medical device of claim 13 , wherein the growth factor is vascular endothelial growth factor (VEGF).

15. A method of promoting endothelialization and reducing platelet adhesion and activation in a tissue in a subject in need thereof, the method comprising:

implanting a medical device in the tissue, wherein the device comprises: a body having at least a first surface;

a plurality of nanotubes formed on the first surface of the body;

at least one polyelectrolyte layer deposited on the nanotubes comprising:

a polycation layer; and

a polyanion layer,

wherein the nanotubes and the polyelectrolyte layers form a nanopatterned structure on the first surface of the body of the medical device to promote endothelialization and reduce platelet adhesion and activation.

16. The method of claim 15 , wherein the medical device is a vascular stent.

17. The method of claim 15 , wherein at least one of the polycation or polyanion comprises nitric oxide-releasing groups.

18. The method of claim 17 , wherein the surface of the device releases nitric oxide over a period of time.

19. The medical device of claim 18 , wherein the device releases nitric oxide at a rate of about 5 nmol/s to about 500 nmol/s.

20. The medical device of claim 19 , wherein the device releases nitric oxide for a period of at least about 2 to about 3 weeks.

21. The method of claim 15 , wherein the polycation comprises nitric oxide-releasing groups.

22. The method of claim 15 , wherein the polyanion comprises nitric oxide-releasing groups.

23. The method of claim 15 , wherein the nanotubes comprise titanium, a titanium alloy, a titanium oxide, or stainless steel.

24. The method of claim 15 , wherein the polycation is chitosan.

25. The method of claim 15 , wherein the polyanion is a glycosaminoglycan.

26. The method of claim 25 , wherein the glycosaminoglycan is selected from heparin, heparan sulfate, chondroitin sulfate, keratan sulfate, dextran sulfate, a sulfated polysaccharide, and a sulfate-containing polylelectrolyte.

27. The method of claim 15 , wherein the medical device further comprises a growth factor adsorbed on to the at least one polyelectrolyte layer.

28. The method of claim 27 , wherein the growth factor is VEGF.

29. A method of modifying a surface of a medical device to promote (re)endothelialization and reduce platelet adhesion and activation, the method comprising:

forming nanotubes on at least a first surface of the medical device and depositing at least one polyelectrolyte layer on the nanotubes comprising:

depositing a polycation layer on the nanotubes;

rinsing the surface;

depositing a polyanion layer on the nanotubes; and

rinsing the surface,

wherein the nanotubes and the polyelectrolyte layers form a nanopatterned structure on the first surface of the medical device to promote (re)endothelialization and reduce platelet adhesion and activation.

30. The method of claim 29 , further comprising modifying at least one of the polycation or the polyanion with nitric oxide-releasing groups.

31. The method of claim 30 , wherein the surface of the device releases nitric oxide over a period of time.

32. The medical device of claim 31 , wherein the device releases nitric oxide at a rate of about 5 nmol/s to about 500 nmol/s.

33. The medical device of claim 32 , wherein the device releases nitric oxide for a period of at least about 2 to about 3 weeks.

34. The method of claim 29 , wherein forming the nanotubes comprises anodizing the first surface of the medical device.

35. The method of claim 29 , further comprising repeating the alternation of the polycation layer and polyanion layer until a desired thickness is reached.

36. The method of claim 29 , wherein the nanotubes comprise titanium, a titanium alloy, a titanium oxide, or stainless steel.

37. The method of claim 29 , wherein the polycation is chitosan.

38. The method of claim 29 , wherein the polyanion is selected from heparin, heparan sulfate, and chondroitin sulfate.

39. The method of claim 29 , further comprising adsorbing VEGF to the polyelectrolyte layers.

Assignments (3)
CONFIRMATORY LICENSE Recorded Oct 9, 2018
From: COLORADO STATE UNIVERSITY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 047104/0439 →
CONFIRMATORY LICENSE Recorded Nov 18, 2015
From: COLORADO STATE UNIVERSITY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 037069/0486 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 12, 2015
From: KIPPER, MATTHEW; POPAT, KETUL; REYNOLDS, MELISSA; LESZCZAK, VICTORIA; ROMERO, RAIMUNDO
To: COLORADO STATE UNIVERSITY RESEARCH FOUNDATION
Reel/Frame 036771/0499 →
Continuity (2)
Provisional Application 61811574 · Apr 12, 2013
Related Publication 20160067388A1 · Mar 10, 2016