Implantable device for promoting repair of a body lumen

• US 7,235,096 B1
• Filed: 08/25/1999
• Issued: 06/26/2007
• Est. Priority Date: 08/25/1998
• Status: Expired due to Fees

• Current Assignee: Tricardia Ventures LLC
• Original Assignee: Tricardia Ventures LLC
• Inventors: Schwartz, Robert S., Van Tassel, Robert A., Holmes, David R. Jr.
• Primary Examiner(s): McDermott; Corrine
• Assistant Examiner(s): SWEET, THOMAS
• Application Number:
  US09/382,275
• Time in Patent Office: 2,862 Days
• Field of Search: 623/1.1, 623/1.13, 623/1.15, 623/1.21, 623/1.39, 623/1.4, 623/1.41, 623/1.42, 623 143- 148
• US Class Current: 623/1.15
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/028 by thermo-dilution
• CPC Class Codes: A61B 5/6862 Stents
• CPC Class Codes: A61B 5/6876 Blood vessel
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials

Abstract

An implantable stent having surface features adapted to promote an organized growth pattern of infiltrating cells when implanted in a tubular organ is provided. The surface features comprise depressions, pores, projections, pleats, channels or grooves in the stent body and are designed to increase turbulence or stagnation in the flow of a liquid, such as blood through the stent, and/or to promote the growth of infiltrating cells in an organized pattern. Alternatively, the invention stent can be populated with living cells prior to implant and can be heatable from an external source of energy, thereby inducing production of therapeutic bioactive agents from ingrowing cells. The invention also provides an implantable heatable stent for transcutaneously monitoring the flow of fluid through a lumen into which the stent is implanted by measuring the rate at which the heated stent cools in response to blood flow when the source of heat is removed.

Claims

1. An implantable stent comprising a tubular stent body having a plurality of interconnected microholes distributed throughout said stent body substantially uniformally along the entire length of said stent body, said plurality of microholes being sufficiently small so as to promote an organized growth pattern of infiltrating cells throughout said stent body, and said stent body being otherwise substantially free of holes larger than said microholes, and said stent body is formed from a fibrous three dimensional non-woven matrix.

2. The stent according to claim 1 wherein the organized growth pattern is angiogenesis.

3. The stent according to claim 1 wherein the surface features comprise a plurality of depressions in the surface of at least a portion of the stent body.

4. The stent according to claim 3 wherein the depressions have an average volume per depression in the range from about 10 μ

m to about 100 μ

m.

5. The stent according to claim 3 wherein the depressions are in a regular pattern on at least the interior surface of the stent body.

6. The stent according to claim 5 wherein the pattern is selected to create turbulence in the flow of fluid through the stent body.

7. The stent according to claim 6 wherein the turbulence increases fluid shear stress upon the infiltrating cells.

8. The stent according to claim 1 wherein the surface features comprise a plurality of longitudinal pleats, grooves or channels in the stent body.

9. The stent according to claim 8 wherein the pleats, grooves, or channels have an average height or depth in the range from about 10 μ

m to about 100 μ

m and an average distance from center to center in the range from about 10 μ

m to about 100 μ

m.

10. The stent according to claim 8 wherein the pleats, grooves, or channels are spaced and sized to promote create fluid shear stress in flow of blood through the stent and/or to cause alignment of cells that infiltrate the pleats, grooves, or channels.

11. The stent according to claim 1 wherein the surface features comprise pores in the stent body having an average diameter in the range from about 30 microns to about 65 microns.

12. The stent according to claim 11 wherein the stent body is formed from a polymer or a non-woven matrix of metal fibers.

13. The stent according to claim 12 wherein the metal fibers are stainless steel, tantalum, elgiloy, nitinol, or a suitable combination thereof, and have a diameter in the range from about 1 micron to 25 microns.

14. The stent according to claim 12 wherein the non-woven matrix has a porosity of about 50% to about 85%.

15. The stent according to claim 14 wherein the porosity is at least about 70%.

16. The stent according to claim 1 wherein the surface features comprise an array of upstanding projections that promote shear turbulence in blood flow along at least a portion of the surface of the stent body.

17. The stent according to claim 16 wherein the projections have an average height of from about 10 μ

m to about 100 μ

m.

18. The stent according to claim 17 wherein the projections are an orderly array of hooks or stalks having a diameter to height ratio of from about 10:

1 to about 100;

1.

19. The stent according to claim 18 wherein the hooks or stalks have a uniform spacing of from about 10 μ

m to about 200 μ

m from center to center.

20. The stent according to claim 1 wherein the stent body is formed of a polymeric material having pores with an average pore diameter in the range from about 30 microns to about 65 microns.

21. The stent according to claim 1 wherein the surface features comprise a layer of a biocompatible substance that expands or thickens in an aqueous environment to assume a three-dimensional form, wherein the layer covers at least a portion of the surface of the stent body.

22. The stent according to claim 21 wherein the three dimensional form comprises an array of upstanding projections.

23. The stent according to claim 21 wherein the layer comprises a hydrogel.

24. The stent according to claim 21 wherein the three dimensional form is porous.

25. The stent according to claim 21 wherein the expandable substance is a hydrogel.

26. The stent according to claim 1 wherein the surface features comprise a pattern of hydrogel markings on at least a portion of the surface of the stent body.

27. The stent according to claim 26 wherein the pattern of markings comprises a plurality of dots, lines, curvilinear tracings, or a mixture thereof.

28. The stent according to claim 27 wherein the markings are distributed over the interior surface of the stent body.

29. The stent according to claim 1 wherein the stent is diametrically adjustable.

30. The stent according to claim 1 wherein the stent further comprises a transcutaneously energized heating mechanism attached to the stent body.

31. The stent according to claim 30 wherein the heating mechanism is adapted to controllably heat the stent to temperatures from about 38°

C. to about 49°

C. when the stent is implanted.

32. The stent according to claim 31 wherein the heating mechanism comprises a thermostat/heat regulator.

33. The stent according to claim 32 wherein the thermostat/heat regulator comprises one or more heat sensors and telemetering device for conveying the temperature sensed by each sensor.

34. The stent according to claim 33 wherein the telemetering device comprises an antenna coil wrapped about the surface of the stent and a hybrid integrated circuit chip in communication with the antenna coil, whereby energy picked up by the antenna coil powers the hybrid circuit.

35. The stent according to claim 33 wherein the thermostat/heat regulator comprises at least two heat sensors located at opposite ends of the stent body.

36. The stent system according to claim 34 wherein each of the sensors produces a temperature output signal corresponding to the temperature sensed and wherein the stent system further comprises a monitor in spaced juxtaposition to the stent for transcutaneously receiving the output signal from each sensor.

37. The stent according to claim 34 wherein the heat sensors have sufficient sensitivity to detect a temperature difference as small as 0.1°

C. from one end of the stent to the other end.

38. The stent system according to claim 37 wherein the energy source delivers electromagnetic energy to the stent in the form of radio frequency energy, microwave energy, or a magnetic field.

39. A stent system comprising a stent according to claim 37 in spaced juxtaposition to an energy source for transcutaneously applying energy to the stent, thereby causing the temperature of the stent to increase to the temperature from about 38°

C. to about 49°

C.

40. The stent system according to claim 38 wherein the monitor is in communication with the energy source and signals from the monitor activate the energy source.

41. A stent system comprising a stent according to claim 1 in spaced juxtaposition to an energy source for transcutaneously applying energy to the stent, thereby causing the temperature of the stent to increase to a temperature above body temperature.

42. An active stent comprising a stent according to claim 1 and further comprising live cells growing in said interconnected microholes.

43. The active stent according to claim 42 wherein the live cells are selected from the group consisting of endothelial cells, smooth muscle cells, leukocytes, monocytes, epithelial cells, polymorphonuclear leukocytes, lymphocytes, basophils, fibroblasts, stem cells, epithelial cells and eosinophils.

44. The active stent according to claim 43 wherein the live cells are smooth muscle cells, epithelial cells, or endothelial cells.

45. The active stent according to claim 42 wherein the stent further comprises a transcutaneously energized heating mechanism adapted to control the heating of the stent to a temperature sufficient to cause the live cells to increase production of one or more bioactive agents.

46. The active stent according to claim 45 wherein the bioactive agent stimulates angiogenesis and/or capillary formation.

47. The active stent according to claim 46 wherein the bioactive agent is vascular endothelial growth factor (VEGF), a fibroblast growth factor (FGF), angiopoietin 1, or thrombin.

48. The active stent according to claim 45 wherein the bioactive agent modifies vascular structure in the hematologic system.

49. The active stent according to claim 48 wherein the bioactive agent modifies platelet function.

50. The active stent according to claim 45 wherein the bioactive agent is an anti-proliferative, anti-restenotic, or apoptotic agent.

51. The active stent according to claim 50 wherein the bioactive agent is nitric oxide.

52. The active stent according to claim 45 wherein the agent increases production of nitric oxide in the cells in or around the stent.

53. The active stent according to claim 42 further comprising means carried by the stent body for telemetering stent temperature information to an external energy source.

54. The stent according to claim 1, wherein said stent body is penetrated with said microholes.

55. The stent according to claim 1, wherein said microholes extend throughout said stent body so as to promote cell growth outward into said stent tube and into attachment with cells at either end of said stent.

56. A method for measuring flow of a fluid through a body lumen, said method comprising:

implanting a stent according to claim 33 into a body lumen having a flow of fluid therethrough,

energizing the implanted stent transcutaneously to raise the temperature thereof above body temperature,

monitoring transcutaneously the output from one or more of the temperature sensors upon cessation of the energizing to determining the cooling rate at each of the one or more sensors, and

obtaining the flow rate of the fluid through the stent from the cooling rate at the one or more sensors.

57. The method according to claim 56 wherein the temperature of the stent is raised from 0.1°

C. about 12°

C. above body temperature.

58. The method according to claim 56 wherein the fluid is blood and the stent is implanted in a blood vessel.

59. The method according to claim 56 wherein the cooling rate is determined at least two of the sensors and the flow rate is obtained as a function of the distance between the two sensors.

60. The method according to claim 56 wherein the cooling rate is determined using the temperature difference between at least two of the temperature sensors.

61. The method according to claim 56 wherein the method is repeated periodically to monitor occlusion of the lumen.

62. A method for treating a tubular body organ in a subject in need thereof said method comprising:

promoting the ingrowth of living cells in a stent having a plurality of interconnected microholes distributed within said stent body substantially uniformally along the entire length of said stent body, said plurality of microholes being sufficiently small in size so as to promote ingrowth of the cells, and said stent body being otherwise substantially free of holes larger than said microholes, and,

implanting the stent into the tubular organ of the subject prior to or following the promoting of the ingrowth of the living cells so as to treat the tubular organ, and said stent body is formed from a fibrous three dimensional non-woven matrix.

63. The method according to claim 62 wherein the living cells are donor or autologous cells.

64. The method according to claim 63 wherein the living cells are autologous.

65. The method according to claim 62 wherein the treatment further comprises promoting or inhibiting angiogenesis within the stent body.

66. The method according to claim 62 wherein the body organ is a blood vessel.

67. The method according to claim 62 wherein the treating comprises holding the cells in a specific pattern or stimulating the growth of the cells into an organized growth pattern.

68. The method according to claim 67 wherein the organized growth pattern develops into an organized cellular structure within the stent body.

69. The method according to claim 62 wherein the stent can be heated by transcutaneously applied energy and the method further comprises transcutaneously energizing the heating of the stent to a temperature above normal body temperature sufficient to cause the living cells to express one or more bioactive agents.

70. The method according to claim 69 wherein the one or more bioactive agents promotes or inhibits angiogenesis within the living cells growing in the stent.

71. The method according to claim 69 wherein at least some of the living cells contain a DNA construct encoding and expressing a bioactive agent under the control of an operatively associated exogeneous heat shock promoter.

72. The method according to claim 71 further comprising turning the promoter on or off by controlling the heating of the stent.

73. The method according to claim 71 wherein the heat shock promoter is derived from E. Coli or Drosophilia.

74. The method according to claim 71 wherein the treating further comprises chronically releasing the bioactive agent on demand by transcutaneously energizing the stent.

75. The method according to claim 69 wherein the temperature to which the stent body is heated remains below a value lethal to the living cells.

76. The method according to claim 75 wherein the temperature to which the stent body is heated is in a range from about 38°

C. to about 49°

C.

77. The method according to claim 62 wherein the living cells are endothelial cells, smooth muscle cells, leukocytes, monocytes, polymorphonuclear leukocytes, lymphocytes, basophils, fibroblasts, stem cells, epithelial cells or eosinophils.

78. The method according to claim 62, wherein said stent body is penetrated with said microholes.

79. The method according to claim 62, wherein after the implanting of said stent, said ingrowth of living cells is promoted such that said cells grow outward into said stent tube and into attachment with cells at either end of said stent.