Photochemical tissue bonding
View Patent ↗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.
1. 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) at a concentration of less than 1.0% weight per volume to form a skin tissue-RB complex; and
applying electromagnetic energy having a wavelength of at least 488 nm 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 cross-linkable substrate,
thereby promoting a partial or complete repair of the skin lesion.
2. The method of claim 1 , wherein the subject is a human.
3. The method of claim 1 , wherein the skin lesion is caused by a laceration, burn, surgical procedure or ulceration.
4. The method of claim 1 , wherein repair of the lesion comprises a seal that is resistant to shear stress.
5. 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.
6. 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.
7. 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.
8. The method of claim 1 , wherein the electromagnetic energy applied is less than 2000 J/cm 2 .
9. The method of claim 1 , wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm 2 .
10. The method of claim 1 , wherein the electromagnetic energy is applied at an irradiance of about 0.60 W/cm 2 .
11. A method for bonding musculoskeletal tissue with a tissue seal, comprising:
contacting a first musculoskeletal tissue, a second musculoskeletal tissue, and rose bengal at a concentration of less than 1.0% weight per volume to form a musculoskeletal tissue-photosensitizer complex; and
applying electromagnetic energy having a wavelength of at least 488 nm to the musculoskeletal tissue-photosensitizer complex in a manner effective to bond the musculoskeletal tissues,
wherein the musculoskeletal tissues are not contacted with an exogenous cross-linkable substrate,
thereby creating a tissue seal between the first and second tissues.
12. The method of claim 11 , wherein the first and second musculoskeletal tissues are independently selected from the group consisting of tendon, ligament and cartilage.
13. The method of claim 11 , wherein the contacting step occurs ex vivo.
14. The method of claim 11 , wherein the contacting step occurs in vivo in a subject.
15. The method of claim 14 , wherein the subject is a human.
16. The method of claim 11 , wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without substantial thermal tissue damage.
17. The method of claim 11 , wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without more than a 15° C. rise in temperature.
18. The method of claim 11 , wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without more than a 10° C. rise in temperature.
19. The method of claim 11 , wherein the application of electromagnetic energy to the musculoskeletal tissue-photosensitizer complex occurs without more than a 3° C. rise in temperature.
20. The method of claim 11 , wherein the electromagnetic energy applied is less than 2000 J/cm 2 .
21. The method of claim 11 , wherein the electromagnetic energy applied is between 125 and 750 J/cm 2 .
22. The method of claim 11 , wherein the electromagnetic energy applied is between 250 and 750 J/cm 2 .
23. The method of claim 11 , wherein the electromagnetic energy applied is between 250 and 500 J/cm 2 .
24. The method of claim 11 , wherein the electromagnetic energy is applied at an irradiance less than 1.5 W/cm 2 .
25. The method of claim 11 , wherein the electromagnetic energy is applied at an irradiance less than 1.0 W/cm 2 .
26. The method of claim 11 , wherein the electromagnetic energy is applied at an irradiance of between 0.1 and 1.0 W/cm 2 .
27. The method of claim 11 , wherein the two musculoskeletal tissues comprise the ends of a ruptured tendon.
28. The method of claim 1 or 11 , wherein the rose bengal is applied at a concentration of less than 0.5% weight per volume in phosphate buffered saline.
29. The method of claim 1 or 11 , wherein the rose bengal is applied at a concentration between 0.1 and 0.5% weight per volume in phosphate buffered saline.
30. The method of claim 11 , wherein immediately after joining, the bonded tendon has a tensile strength which is greater than an untreated tendon.