Photochemical tissue bonding

• US 20060212070A1
• Filed: 08/16/2005
• Published: 09/21/2006
• Est. Priority Date: 02/11/2000
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Redmond, Robert W., Kochevar, Irene E.
• Granted Patent: US 8,092,490 B2
• Time in Patent Office: Days
• US Class Current: 606/214
• CPC Class Codes: A61B 2017/005 hardenable using external energy source, e.g. laser, ultrasound
• CPC Class Codes: A61B 2017/00508 using laser
• CPC Class Codes: A61B 2017/00517 using laser
• CPC Class Codes: A61F 2009/00853 Laser thermal keratoplasty or radial keratotomy
• CPC Class Codes: A61F 2009/00872 Cornea
• CPC Class Codes: A61F 2009/00887 Cataract
• CPC Class Codes: A61F 9/008 using laser
• CPC Class Codes: A61F 9/0081 Transplantation
• CPC Class Codes: A61F 9/00821 for coagulation
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials

Abstract

Photochemical tissue bonding methods include the application of a photosensitizer to a tissue and/or tissue graft, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for tissue adhesion, such as in wound closure, tissue grafting, skin grafting, musculoskeletal tissue repair, ligament or tendon repair and corneal repair.

Claims

1. A method for adhering tissue, comprising:

contacting a first tissue, a second tissue, and at least one photosensitizer agent to form a tissue-photosensitizer complex; and

applying electromagnetic energy to the tissue-photosensitizer complex in a manner effective to bond the tissue,

wherein the tissue is not contacted with an exogenous protein or peptide which is cross linked by the application of electromagnetic energy,

thereby creating a tissue seal between the first and second tissue.

2. The method of claim 1, wherein the tissue is selected from the group consisting of cardiovascular, neurological, gastrointestinal, renal, urological, occular, oral, respiratory, otolaryngological, dermatological, gynecological, genital and connective tissue.

3. The method of claim 1, wherein the tissue is skin.

4. The method of claim 1, wherein the at least one photosensitizer agent is selected from the group consisting of a xanthene, flavin and pyridine.

5. The method of claim 4, wherein the xanthene is Rose Bengal.

6. The method of claim 4, wherein the flavin is riboflavin-5-phosphate.

7. The method of claim 4, wherein the pyridine is N-hydroxypyridine-2-(1H)-thione.

8. The method of claim 1, wherein the contacting steps occurs ex vivo.

9. The method of claim 1, wherein the contacting steps occurs in vivo in a subject.

10. The method of claim 9, wherein the subject is a human.

11. The method of claim 1, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without substantial thermal tissue damage.

12. The method of claim 1, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 15°

C. rise in temperature.

13. The method of claim 1, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 10°

C. rise in temperature.

14. The method of claim 1, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 3°

C. rise in temperature.

15. The method of claim 1, wherein the electromagnetic energy applied is less than 2000 J/cm².

16. The method of claim 1, wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm².

17. The method of claim 1, wherein the electromagnetic energy is applied at an irradiance of about 0.60 W/cm².

18. A method for grafting tissue, comprising:

contacting a first tissue, a second tissue comprising a tissue graft, and at least one photosensitizer agent to form a tissue-photosensitizer complex; and

applying electromagnetic energy to the tissue-photosensitizer complex in a manner effective to bond the tissue,

wherein the tissue is not contacted with an exogenous protein or peptide which is cross linked by the application of electromagnetic energy,

thereby creating a tissue seal between the first and second tissue.

19. The method of claim 18, wherein the first tissue is selected from the group consisting of cardiovascular, neurological, gastrointestinal, renal, urological, occular, oral, respiratory, otolaryngological, dermatological, gynecological, genital and connective tissue.

20. The method of claim 18, wherein the tissue is skin.

21. The method of claim 18, wherein the at least one photosensitizer agent is selected from the group consisting of a xanthene, flavin and pyridine.

22. The method of claim 21, wherein the xanthene is Rose Bengal.

23. The method of claim 21, wherein the flavin is riboflavin-5-phosphate.

24. The method of claim 21, wherein the pyridine is N-hydroxypyridine-2-(1H)-thione.

25. The method of claim 18, wherein the contacting steps occurs ex vivo.

26. The method of claim 18, wherein the contacting steps occurs in vivo in a subject.

27. The method of claim 26, wherein the subject is a human.

28. The method of claim 18, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without substantial thermal tissue damage.

29. The method of claim 18, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 15°

C. rise in temperature.

30. The method of claim 18, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 10°

C. rise in temperature.

31. The method of claim 18, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 3°

C. rise in temperature.

32. The method of claim 18, wherein the electromagnetic energy applied is less than 2000 J/cm².

33. The method of claim 18, wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm².

34. The method of claim 18, wherein the electromagnetic energy is applied at an irradiance of about 0.60 W/cm².

35. A method for repairing a skin lesion, comprising:

contacting a skin lesion, a tissue comprising a skin graft, and at least one photosensitizer agent to form a skin tissue-photosensitizer complex; and

applying electromagnetic energy to the skin tissue-photosensitizer complex in a manner effective to bond the complex,

wherein the skin lesion and/or graft is not contacted with an exogenous protein or peptide which is cross-linked by the application of electromagnetic energy,

thereby promoting a partial or complete repair of the lesion.

36. The method of claim 35, wherein the skin lesion is caused by a laceration, burn, surgical procedure or ulceration.

37. The method of claim 35, wherein repair of the skin lesion comprises a seal that is resistant to shear stress.

38. The method of claim 35, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 15°

C. rise in temperature.

39. The method of claim 35, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 10°

C. rise in temperature.

40. The method of claim 35, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 3°

C. rise in temperature.

41. The method of claim 35, wherein the electromagnetic energy applied is less than 2000 J/cm².

42. The method of claim 35, wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm².

43. The method of claim 35, wherein the electromagnetic energy is applied at an irradiance of about 0.60 W/cm².

44. The method of claim 35, wherein the at least one photosensitizer agent is selected from the group consisting of a xanthene, flavin and pyridine.

45. The method of claim 44, wherein the xanthene is Rose Bengal.

46. The method of claim 44, wherein the flavin is riboflavin-5-phosphate.

47. The method of claim 44, wherein the pyridine is N-hydroxypyridine-2-(1H)-thione.

48. A method for repairing a skin lesion in vivo in a subject, comprising:

contacting a skin lesion, a tissue comprising a skin graft and Rose Bengal (RB) to form a skin tissue-RB complex; and

applying electromagnetic energy to the skin tissue-RB complex in a manner effective to bond the complex,

wherein the skin lesion and/or graft is not contacted with an exogenous protein or peptide which is cross-linked by the application of electromagnetic energy,

thereby promoting a partial or complete repair of the skin lesion.

49. The method of claim 48, wherein the subject is a human.

50. The method of claim 48, wherein the skin lesion is caused by a laceration, burn, surgical procedure or ulceration.

51. The method of claim 48, wherein repair of the lesion comprises a seal that is resistant to shear stress.

52. The method of claim 48, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 15°

C. rise in temperature.

53. The method of claim 48, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 10°

C. rise in temperature.

54. The method of claim 48, wherein the application of electromagnetic energy to the tissue-photosensitizer complex occurs without more than a 3°

C. rise in temperature.

55. The method of claim 48, wherein the electromagnetic energy applied is less than 2000 J/cm².

56. The method of claim 48, wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm².

57. The method of claim 48, wherein the electromagnetic energy is applied at an irradiance of about 0.60 W/cm².

58. A method for bonding musculoskeletal tissue with a tissue seal, comprising:

contacting a first musculoskeletal tissue, a second musculoskeletal tissue, and at least one photosensitizer agent to form a musculoskeletal tissue-photosensitizer complex; and

applying electromagnetic energy to the musculoskeletal tissue-photosensitizer complex in a manner effective to bond the musculoskeletal tissue,

wherein the musculoskeletal tissue is not contacted with an exogenous protein or peptide which is cross linked by the application of electromagnetic energy,

thereby creating a tissue seal between the first and second tissue.

59. The method of claim 58, wherein the first and second musculoskeletal tissues are independently selected from the group consisting of tendon, ligament and cartilage.

60. The method of claim 58, wherein the at least one photosensitizer agent is selected from the group consisting of a xanthene, flavin and pyridine.

61. The method of claim 60, wherein the xanthene is Rose Bengal.

62. The method of claim 60, wherein the flavin is riboflavin-5-phosphate.

63. The method of claim 60, wherein the pyridine is N-hydroxypyridine-2-(1H)-thione.

64. The method of claim 58, wherein the contacting step occurs ex vivo.

65. The method of claim 58, wherein the contacting step occurs in vivo in a subject.

66. The method of claim 65, wherein the subject is a human.

67. The method of claim 58, wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without substantial thermal tissue damage.

68. The method of claim 58, wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without more than a 15°

C. rise in temperature.

69. The method of claim 58, wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without more than a 10°

C. rise in temperature.

70. The method of claim 58, wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without more than a 3°

C. rise in temperature.

71. The method of claim 58, wherein the electromagnetic energy applied is less than 2000 J/cm².

72. The method of claim 58, wherein the electromagnetic energy applied is between 125 and 750 J/cm².

73. The method of claim 58, wherein the electromagnetic energy applied is between 250 and 750 J/cm².

74. The method of claim 58, wherein the electromagnetic energy applied is between 250 and 500 J/cm².

75. The method of claim 58, wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm².

76. The method of claim 58, wherein the electromagnetic energy is applied at an irradiance less than 1.0 W/cm².

77. The method of claim 58, wherein the electromagnetic energy is applied at an irradiance of between 0.1 and 1.0 W/cm².

78. The method of claim 58, wherein the two musculoskeletal tissues comprise the ends of a ruptured tendon.

79. The method of claim 61, wherein the rose bengal is applied at a concentration of less than 1.0 % weight per volume in phosphate buffered saline.

80. The method of claim 61, wherein the rose bengal is applied at a concentration of less than 0.5% weight per volume in phosphate buffered saline.

81. The method of claim 61, wherein the rose bengal is applied at a concentration between 0.1 and 0.5% weight per volume in phosphate buffered saline.

82. The method of claim 58, wherein immediately after joining, the bonded tendon has a tensile strength which is greater than an untreated tendon.