Implantable sensor with biocompatible coating for controlling or inhibiting tissue growth

• US 20060008500A1
• Filed: 07/09/2004
• Published: 01/12/2006
• Est. Priority Date: 07/09/2004
• Status: Active Grant

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Chavan, Abhi, Ross, Jeffrey, Mazar, Scott, Morrissey, Cynthia, Palme, Donald
• Granted Patent: US 8,696,564 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61B 5/00 Measuring for diagnostic purposes radiation diagnosis A61B6/00; diagnosis by ultrasonic, sonic or infrasonic waves A61B8/00; Identification of persons
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

All or a portion of a surface of an implantable sensor is covered with a biocompatible coating formed at least partially of a biomaterial matrix having properties that promote a substantially even growth of tissue cells over the surface of the coating. Additional materials, such as growth factors, agents that recruit endogenous stem cells, and cell adhesion motif arginine, glycine, aspartic acid may be included in the coating. Autologous cells may be added to the coating prior to implantation. The sensor surface may also be textured, by etching or abrading, in order to promote even tissue growth. Alternatively, the sensor surface may be covered with a coating having properties that inhibit the growth of tissue. These coatings may include a biomaterial, a biomaterial matrix having a drug, such as a sirolimus or a steroid, an active component, or a self assembled monolayer.

Claims

1. A sensor comprising:

a sensor surface; and

a biocompatible coating comprising a biomaterial matrix, the coating covering at least a portion of the sensor surface and having properties that promote a substantially even growth of tissue cells over the surface of the coating.

2. The sensor of claim 1 wherein the biomaterial matrix comprises a natural polymer.

3. The sensor of claim 2 wherein the natural polymer comprises extracellular matrix material.

4. The sensor of claim 3 wherein the extracellular matrix material is selected from the group consisting of intestine submucosa and urinary bladder matrix.

5. The sensor of claim 2 wherein the natural polymer comprises a protein.

6. The sensor of claim 5 wherein the protein is selected from the group consisting of collagen, fibrin, elastin, fibrillin, fibronectin, and laminin.

7. The sensor of claim 2 wherein the natural polymer comprises proteoglycans.

8. The sensor of claim 2 wherein the natural polymer comprises phosphytidyl choline.

9. The sensor of claim 1 wherein the biomaterial matrix comprises a synthetic polymer.

10. The sensor of claim 9 wherein the synthetic polymer is selected from the group consisting of polyhydroxyvalerate, poly(L)lactic acid, polycaprolactone, polylactide-co-glycolide, polyhydroxybutyrate, polyhydroxybutyrate-co-valerate, polydioxanone, polyorthoesters, polyanhydrides, polyacetic, polyglycolic acid, poly(D,L)lactic acid, polyglycolic acid-co-trimethylene carbonate, polysebacic acid, polylactic-co-sebacic acid, polyglycolic-co-sebacid acid, polyphosphoesters, polyphosphoester urethanes, polyamino acids, ion exchange resins, cyanoacrylates, polytrimethylene carbonate, polyiminocarbonate, copolyether-esters, polyalkylene oxalates and polyphosphazenes.

11. The sensor of claim 9 wherein the synthetic polymer is selected from the group consisting of polyurethanes, silicones and polyesters.

12. The sensor of claim 9 wherein the synthetic polymer is selected from the group consisting of polyolefin, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl ethers, polyvinylidene halides, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, polyvinyl esters, copolymers of vinyl monomers with each other and olefins, polyamides, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, rayon and rayon-triacetate.

13. The sensor of claim 1 wherein the coating further comprises a growth factor.

14. The sensor of claim 13 wherein the growth factor is selected from the group consisting of vascular endothelial cell growth factor (VEGF) and isoforms, basic fibroblast growth factor (bFGF), platelet-induced growth factor (PDGF), transforming growth factor beta (TGF.b), acidic fibroblast growth factor (aFGF), osteonectin, angiopoietin 1, angiopoietin 2, insulin-like growth factor (IGF), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor BB (PDGF-BB), platelet-derived growth factor AB (PDGF-AB), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the like, or functional fragments thereof.

15. The sensor of claim 1 wherein the coating further comprises an agent that recruits endogenous stem cells.

16. The sensor of claim 15 wherein the agent is selected from the group consisting of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF-1), stromal-derived factor (SDF-1), insulin-like growth factor (IGH) and hepatocyte growth factor (HGF).

17. The sensor of claim 1 wherein the coating further comprises cell adhesion motif arginine, glycine, aspartic acid (RGD).

18. A sensor comprising:

a sensor surface formed of a metallic material;

wherein at least a portion of the sensor surface is textured to promote a substantially even growth of tissue cells over the portion.

19. A sensor comprising:

a sensor surface; and

a biocompatible coating comprising a biomaterial matrix and autologous cells, the coating covering at least a portion of the surface and having properties that promote a substantially even growth of tissue cells over the surface of the coating.

20. The sensor of claim 19 wherein the biomaterial matrix comprises a natural polymer.

21. The sensor of claim 20 wherein the natural polymer comprises extracellular matrix material.

22. The sensor of claim 21 wherein the extracellular matrix material is selected from the group consisting of intestine submucosa and urinary bladder matrix.

23. The sensor of claim 20 wherein the natural polymer comprises a protein.

24. The sensor of claim 23 wherein the protein is selected from the group consisting of collagen, fibrin, elastin, fibrillin, fibronectin, and laminin.

25. The sensor of claim 20 wherein the natural polymer comprises proteoglycans.

26. The sensor of claim 20 wherein the natural polymer comprises phosphytidyl choline.

27. The sensor of claim 19 wherein the biomaterial matrix comprises a synthetic polymer.

28. The sensor of claim 27 wherein the synthetic polymer is selected from the group consisting of polyhydroxyvalerate, poly(L)lactic acid, polycaprolactone, polylactide-co-glycolide, polyhydroxybutyrate, polyhydroxybutyrate-co-valerate, polydioxanone, polyorthoesters, polyanhydrides, polyacetic, polyglycolic acid, poly(D,L)lactic acid, polyglycolic acid-co-trimethylene carbonate, polysebacic acid, polylactic-co-sebacic acid, polyglycolic-co-sebacid acid, polyphosphoesters, polyphosphoester urethanes, polyamino acids, ion exchange resins, cyanoacrylates, polytrimethylene carbonate, polyiminocarbonate, copolyether-esters, polyalkylene oxalates and polyphosphazenes.

29. The sensor of claim 27 wherein the synthetic polymer is selected from the group consisting of polyurethanes, silicones and polyesters.

30. The sensor of claim 27 wherein the synthetic polymer is selected from the group consisting of polyolefin, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl ethers, polyvinylidene halides, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, polyvinyl esters, copolymers of vinyl monomers with each other and olefins, polyamides, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, rayon and rayon-triacetate.

31. The sensor of claim 27 wherein the synthetic polymer is selected from the group consisting of polymers or copolymers of caprolactones, carbonates, amides, amino acids with reactive side chains including lysine, arginine, aspartic acid, glutamic acid, serine, threonine, tyrosine and cysteine, or their enantiomers, orthoesters, acetals, cyanoacrylates and degradable urethanes, as well as copolymers of these with straight chain or branched, substituted or unsubstituted, alkanyl, haloalkyl, thioalkyl, aminoalkyl, alkenyl, or aromatic hydroxy- or di-carboxylic acids.

32. The sensor of claim 19 wherein the autologous cells comprises stem cells.

33. The sensor of claim 32 wherein the stem cells are selected from the group consisting of mesenchymal stem cell (MSC), endothelial progenitor cell (EPC), smooth muscle cell (SMC), endothelial cell, hematopoietic stem cells, multipotent adult progenitor cells, adult stem cells and embryonic stem cells.

34. The sensor of claim 19 wherein the autologous cells comprise differentiated cells derived from stem cells.

35. A sensor comprising:

a sensor surface; and

a biocompatible coating comprising a biomaterial covering at least a portion of the surface, the coating having properties that inhibit the growth of tissue over the surface of the coating.

36. The sensor of claim 35 wherein the biomaterial is selected from the group consisting of polytetraflouroethylene and polyethylene glycol.

37. The sensor of claim 35 wherein the biomaterial comprises an anti-thrombogenic material.

38. The sensor of claim 37 wherein the anti-thrombogenic material comprises a hydro-gel.

39. The sensor of claim 38 wherein the hydro-gel is selected from a group of poly-ethylene oxide, albumin, hydrophilic poly-methacrylates and hydrophilic poly urethanes.

40. A sensor comprising:

a sensor surface; and

a biocompatible coating covering at least a portion of the surface, the coating comprising a biomaterial matrix and an active component, wherein the active component imparts properties to the coating that inhibits the growth of tissue over the surface of the coating.

41. The sensor of claim 40 wherein the biomaterial matrix comprises a natural polymer.

42. The sensor of claim 41 wherein the natural polymer comprises extracellular matrix material.

43. The sensor of claim 42 wherein the extracellular matrix material is a material selected from the group consisting of intestine submucosa and urinary bladder matrix.

44. The sensor of claim 41 wherein the natural polymer comprises a protein.

45. The sensor of claim 44 wherein the protein is selected from the group consisting of collagen, fibrin, elastin, fibrillin, fibronectin, and laminin.

46. The sensor of claim 44 wherein the natural polymer comprises proteoglycans.

47. The sensor of claim 44 wherein the natural polymer comprises phosphytidyl choline.

48. The sensor of claim 40 wherein the biomaterial matrix comprises a synthetic polymer.

49. The sensor of claim 48 wherein the synthetic polymer is selected from the group consisting of polyhydroxyvalerate, poly(L)lactic acid, polycaprolactone, polylactide-co-glycolide, polyhydroxybutyrate, polyhydroxybutyrate-co-valerate, polydioxanone, polyorthoesters, polyanhydrides, polyacetic, polyglycolic acid, poly(D,L)lactic acid, polyglycolic acid-co-trimethylene carbonate, polysebacic acid, polylactic-co-sebacic acid, polyglycolic-co-sebacid acid, polyphosphoesters, polyphosphoester urethanes, polyamino acids, ion exchange resins, cyanoacrylates, polytrimethylene carbonate, polyiminocarbonate, copolyether-esters, polyalkylene oxalates and polyphosphazenes.

50. The sensor of claim 48 wherein the synthetic polymer is selected from the group consisting of polyurethanes, silicones and polyesters.

51. The sensor of claim 48 wherein the synthetic polymer is selected from the group consisting of polyolefin, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl ethers, polyvinylidene halides, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, polyvinyl esters, copolymers of vinyl monomers with each other and olefins, polyamides, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, rayon and rayon-triacetate.

52. The sensor of claim 40 wherein the active component comprises a sirolimus.

53. The sensor of claim 40 wherein the active component comprises a steroid.

54. The sensor of claim 40 wherein the active component comprises at least one anti-thrombotic substance and at least one anti-inflammatory substance.

55. The sensor of claim 54 wherein the anti-thrombotic substance is selected from a group of heparin, sodium heparin, low molecular weight heparin, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogs, D-phe-pro-arg-chloromethylketone, dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antibody, and recombinant hirudin;

and the anti-inflamatory substance is selected from a group of aspirin, diclofenac, etodolac, ibuprofen, ketoprofen, ketorolac, nabumetone, naproxen, oxaprozin, clobetasol, diflucortolone, flucinolone, halcinolonide, halobetasol, dexamethasone, betamethasone, corticol, cortisone, prednisone, and prednisolone.

56. A sensor comprising:

a sensor surface comprising gold; and

a biocompatible coating comprising self-assembled monolayer covering at least a portion of the sensor surface.

57. The sensor of claim 56 wherein the self assembled monolayer comprises pre-formed carboxylic acid alkanethiolate.

58. A sensor comprising:

a sensor surface;

a layer of a metallic material comprising gold covering a portion of the sensor surface; and

a biocompatible coating comprising a self assembled monolayer covering at least a portion of the metallic material layer.

59. The sensor of claim 58 wherein the self assembled monolayer comprises pre-formed carboxylic acid alkanethiolate.

60. A method of monitoring biological activity within a body, said method comprising introducing a sensor in the body in the region to be monitored, wherein the sensor comprises a sensor surface and a biocompatible coating comprising a biomaterial matrix, the coating covering at least a portion of the sensor surface and having properties that promote a substantially even growth of tissue cells over the surface of the coating.

61. The method of claim 60 wherein the biomaterial matrix comprises a polymer.

62. The method of claim 60 wherein the coating further comprises a growth factor.

63. The method of claim 60 wherein the coating further comprises an agent that recruits endogenous stem cells.

64. The method of claim 60 wherein the coating further comprises cell adhesion motif argine, glycine, aspartic acid.

65. The method of claim 60 wherein the coating further comprises autologous cells.

66. The method of claim 65 wherein the biomaterial matrix is coated onto the surface during sensor manufacturing and the autologous cells are added to the biomaterial matrix independent of the manufacturing process and prior to implantation.

67. A method of monitoring biological activity within a body, said method comprising introducing a sensor in the body in the region to be monitored, wherein the sensor comprises a sensor surface formed of a metallic material and at least a portion of the sensor surface is textured to promote a substantially even growth of tissue cells over the portion.

68. A method of monitoring biological activity within a body, said method comprising introducing a sensor in the body in the region to be monitored, wherein the sensor comprises a sensor surface and a biocompatible coating comprising a biomaterial covering at least a portion of the surface, the coating having properties that inhibit the growth of tissue over the surface of the coating.

69. A method of monitoring biological activity within a body, said method comprising introducing a sensor in the body in the region to be monitored, wherein the sensor comprises a sensor surface and a biocompatible coating covering at least a portion of the surface, the coating comprising a biomaterial matrix and an active component, wherein the active component imparts properties to the coating that inhibit the growth of tissue over the surface of the coating.

70. A method of monitoring biological activity within a body, said method comprising introducing a sensor in the body in the region to be monitored, wherein the sensor comprises a sensor surface comprising gold and a biocompatible coating comprising a self-assembled monolayer covering at least a portion of the sensor surface.

71. The method of claim 70 wherein the self assembled monolayer comprises pre-formed carboxylic acid alkanethiolate.

72. A method of monitoring biological activity within a body, said method comprising introducing a sensor in the body in the region to be monitored, wherein the sensor comprises a sensor surface, a layer of a metallic material comprising gold covering a portion of the sensor surface, and a biocompatible coating comprising a self assembled monolayer covering at least a portion of the metallic material layer.

73. The method of claim 72 wherein the self assembled monolayer comprises pre-formed carboxylic acid alkanethiolate.

74. A process of manufacturing a sensor for implantation into a body, said process comprising coating at least a portion of a surface of a sensor with a biocompatible coating comprising a biomaterial matrix, the coating having properties that promote a substantially even growth of tissue cells over the surface of the coating.

75. The process of claim 74 further comprising adding a growth factor to the biomaterial matrix prior to coating.

76. The process of claim 74 further comprising adding an agent that recruits endogenous stem cells to the biomaterial matrix prior to coating.

77. The process of claim 74 further comprising adding cell adhesion motif argine, glycine, aspartic acid to the biomaterial matrix prior to coating.

78. The process of claim 74 wherein the biomaterial matrix allows for the addition of autologous cells independent of the manufacturing process and prior to implantation.

79. A process of manufacturing a sensor for implantation into a body, said process comprising texturing at least a portion of a surface of a sensor to promote a substantially even growth of tissue cells over the portion.

80. A process of manufacturing a sensor for implantation into a body, said process comprising coating at least a portion of a surface of a sensor with a biomaterial covering having properties that inhibit the growth of tissue cells over the surface of the coating.

81. A process of manufacturing a sensor for implantation into a body, said process comprising coating at least a portion of a surface of a sensor with a biocompatible coating comprising a biomaterial matrix and an active component, wherein the active component imparts properties to the coating that inhibit the growth of tissue cells over the surface of the coating.

82. A process of manufacturing a sensor for implantation into a body, said process comprising coating at least a portion of a sensor surface comprising gold with a biocompatible coating comprising a self-assembled monolayer.

83. A process of manufacturing a sensor for implantation into a body, said process comprising:

coating at least a portion of a sensor surface with a layer of a metallic material comprising gold; and

coating at least a portion of the layer of metallic material with a biocompatible coating comprising a self assembled monolayer.