BIORESORBABLE BIOPOLYMER STENT

• US 20160067071A1
• Filed: 04/24/2014
• Published: 03/10/2016
• Est. Priority Date: 04/24/2013
• Status: Abandoned Application

• Current Assignee: Tufts Medical Center Incorporated (Healthcare Realty Trust, Inc.), Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Kaplan, David L., Gil, Eun Seok, Leisk, Gary G., Jose, Rodrigo, Iafrati, Mark
• Application Number:
  US14/785,104
• Publication Number:
  US 20160067071A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/844 folded prior to deployment
• CPC Class Codes: A61F 2/93 circumferentially expandable by using ratcheting locks
• CPC Class Codes: A61F 2/9517 handle assemblies therefor
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2002/825 having longitudinal struts
• CPC Class Codes: A61F 2002/826 more than one stent being applied sequentially
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2220/0033 made by longitudinally pushing a protrusion into a complementary-shaped recess, e.g. held by friction fit
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 31/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/141 Plasticizers
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A bioresorbable biopolymer stents can be deployed within a blood vessel and resorbed by the body over a predetermined time period after the blood vessel has been remodeled. A ratcheting biopolymer stent can include a ratcheting mechanism that allows the biopolymer stent to be deployed on a small diameter configuration and then expanded to a predefined larger diameter configuration wherein after expansion, the ratcheting mechanism locks the biopolymer stent in the expanded configuration. A folding biopolymer stent can be deployed in a folded, small diameter configuration and then expanded to an unfolded configuration having a larger diameter. The bioresorbable biopolymer can include silk fibroin and blend that include silk fibroin materials.

Claims

1. An intraluminal stent implantable in a body lumen comprising:

a cylindrical body portion having an axial length extending along a longitudinal axis, said cylindrical body portion formed of a sheet wherein the cylindrical body portion is formed of a blend comprising silk fibroin and a plasticizer.

2. The intraluminal stent of claim 1, including

a first longitudinal edge and

a second longitudinal edge,

an elongated slot in said sheet along the first longitudinal edge, said elongated slot receiving said second longitudinal edge allowing said cylindrical body portion to be selectively expanded in the body lumen.

3. The intraluminal stent according to claim 2, further comprising a strip connecting the second longitudinal edge to the first longitudinal edge, wherein the strip includes one or more teeth adapted for interlocking the strip in the elongated slot.

4. The intraluminal stent according to claim 3, wherein at least one of the teeth is flexible.

5. The intraluminal stent according to claim 2, further comprising a second slot in the sheet along the first longitudinal edge and a second strip connecting the second longitudinal edge to the first longitudinal edge, wherein the second strip includes one or more teeth adapted for interlocking the strip in the second elongated slot.

6. The intraluminal stent according to claim 1, wherein cylindrical body portion is formed of a blend comprising silk fibroin and a plasticizer in a ratio of 10:

1 to about 1;

1 by dry weight or a ratio of 3;

1 by dry weight.

7. The intraluminal stent according to claim 1 including

at least one tab extending from a first longitudinal edge and

at least one slot extending from the second longitudinal edge to the first longitudinal edge, the slot receiving the at least one tab and allowing the cylindrical body to be selectively expanded in the body lumen;

and

wherein the cylindrical body portion is formed of a blend of silk fibroin and a plasticizer.

8. The intraluminal stent according to claim 7, further comprising a second tab extending from the first longitudinal edge and a second slot extending from the second longitudinal edge to the first longitudinal edge, the second slot receiving the second tab and allowing the cylindrical body to be selectively expanded in the body lumen.

9. The intraluminal stent according to claim 7, wherein the at least one slot includes one or more teeth adapted for interlocking the tab in the at least one slot.

10. The intraluminal stent according to claim 9, wherein at least one of the teeth is flexible.

11. The intraluminal stent according to claim 7, wherein cylindrical body portion is formed of a blend of 75% silk fibroin by dry weight and 25% plasticizer by dry weight.

20. The intraluminal stent according to any of claims 1-19, wherein the blend comprising silk fibroin and plasticizer further comprises an additive.

21. The intraluminal stent according to claim 20, wherein the additive is selected from the group consisting of anti-proliferative agents, biopolymers, nanoparticles (e.g., gold nanoparticles), proteins, peptides, nucleic acids (e.g., DNA, RNA, siRNA, modRNA), nucleic acid analogs, nucleotides, oligonucleotides, peptide nucleic acids (PNA), aptamers, antibodies or fragments or portions thereof (e.g., paratopes or complementarity-determining regions), antigens or epitopes, hormones, hormone antagonists, growth factors or recombinant growth factors and fragments and variants thereof, cell attachment mediators (such as RGD), cytokines, enzymes, small molecules, antibiotics or antimicrobial compounds, toxins, therapeutic agents and prodrugs, small molecules and any combinations thereof.

22. The intraluminal stent according to any of claims 1-21, wherein the cylindrical body portion is a multilayered cylindrical body portion.

23. The intraluminal stent according to claim 22, wherein a first layer and a second layer of the cylindrical body portion each comprise at least one additive.

25. The intraluminal stent according to any of claims 1-24, wherein the cylindrical body portion has an average mechanical stiffness of 1.2 kN/m.

26. The intraluminal stent according to any of claims 1-25, wherein the cylindrical body portion has an average radial strength of 300 mmHg.

27. The intraluminal stent according to any of claims 1-26, wherein the blend material comprises micropores.

28. The intraluminal stent according to claim 27, wherein the stent functions as an endovascular stent graft to prevent the rupturing of weakened blood vessel walls.

29. The intraluminal stent according to any of claims 1-28, wherein the blend comprising silk fibroin and plasticizer further comprises an active agent.

30. The intraluminal stent according to claim 29, wherein the active agent is a therapeutic agent.

31. The intraluminal stent according to any of claims 1-30, wherein the blend comprising silk fibroin and plasticizer further comprises an anti-restenosis agent.

32. The intraluminal stent according to any of claims 1-31, wherein the blend comprising silk fibroin and plasticizer further comprises a cell.

33. A method comprising:

implanting a first intraluminal stent of any of claims 1-32 at a target site in a subject.

34. The method of claim 33, wherein the target site is a tissue.

35. The method of claim 34, further comprising growing cells in or on the stent.

36. The method of claim 33, wherein the target site is a blood vessel.

37. The method of any of claims 33-36, wherein the silk fibroin-based blend material of the stent swells upon implantation at the target site, thereby reducing stent malapposition post-implantation.

38. The method of any of claims 33-37, wherein the stent comprises a therapeutic agent.

39. The method of claim 38, wherein the therapeutic agent is stabilized, upon implantation, for at least 3 months or longer.

40. The method of any of claims 33-39, wherein the stent degrades as a tissue surrounding the target site remodels or regenerates.

41. The method of any of claims 28-37, further comprising implanting a second intraluminal stent of any of claims 1-32 at the same target site upon degradation of the first intraluminal stent.

42. The intraluminal stent according to any of claims 1-32, wherein the plasticizer is selected from the group consisting of glycerol;

ethylene glycol;

propylene glycol;

glyceryl monostearate;

1,2-butylene glycol;

2,3-butylene glycol;

styrene glycol;

polyethylene glycols such as diethylene glycol, triethylene glycol, tetraethylene glycol;

polyethylene glycols;

polyethylene oxides;

monopropylene glycol monoisopropyl ether;

propylene glycol monoethyl ether;

ethylene glycol monoethyl ether;

diethylene glycol monoethyl ether;

sorbitol lactate;

ethyl lactate;

butyl lactate;

ethyl glycolate;

allyl glycolate;

monoethanolamine;

diethanolamine;

triethanolamine;

monisopropanolamine;

triethylenetetramine;

2-amino-2-methyl-1,3-propanediol; and

any combinations thereof.

43. A cell scaffold comprising an intraluminal stent of any of claims 1-32 or 42, wherein the plasticizer is wherein the plasticizer is glycerol and the blend comprising silk fibroin and plasticizer further comprises a cell.

12. An intraluminal stent implantable in a body lumen comprising:

a cylindrical body portion having an axial length extending along a longitudinal axis, said cylindrical body portion formed of a blend of silk fibroin and a plasticizer;

the cylindrical body capable for existing in a folded state having a first diameter and an unfolded state having a second diameter wherein the second diameter is greater than the first diameter.

13. The intraluminal stent according to claim 12, wherein cylindrical body portion is formed of a blend of 75% silk fibroin by dry weight and 25% plasticizer by dry weight.

14. An intraluminal stent implantable in a body lumen comprising a cylindrical body portion having an axial length extending along a longitudinal axis, said cylindrical body portion formed of a blend comprising silk fibroin and a plasticizer;

the bend comprising silk fibroin and plasticizer being prepared in a process that includes;

casting the blend of silk fibroin and plasticizer to form a film.

15. The intraluminal stent according to claim 14, wherein the blend of silk fibroin and plasticizer is cast in a sheet in a flat mold.

16. The intraluminal stent according to claim 15 wherein the cast sheet has a thickness in the range of 150 to 300 micrometers.

17. The intraluminal stent according to claim 14, wherein the blend of silk fibroin and plasticizer is cast on a rod to form a tubular film.

18. The intraluminal stent according to claim 17, wherein the cast tubular film has an inside diameter in the range from 650 micrometers to 4500 micrometers.

19. The intraluminal stent according to claim 17, wherein the cast tubular film has a thickness in the range of 150 to 300 micrometers.

24. The intraluminal stent according to any of claims 19-23, wherein degradation of the blend material or optional release of the additive from the blend material varies with the beta sheet content of silk fibroin in the blend material.