Photochemical tissue bonding

Abstract

Photochemical tissue bonding methods include the application of a photosensitizer to a tissue, e.g., cornea, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for wound repair, or other tissue repair.

1 . A method for creating a tissue seal, comprising: 
 identifying a tissue in need of repair;    contacting the tissue, and optionally a second tissue, with at least one photosensitizer agent to form a tissue-photosensitizer mixture; and    applying electromagnetic energy to the tissue-photosensitizer mixture in a manner effective to produce cross linking of a protein in 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.    
     
     
         2 . The method of  claim 1 , wherein the tissue is corneal tissue.  
     
     
         3 . The method of  claim 1 , wherein the at least one photosensitizer agent is selected from the group consisting of Rose Bengal, riboflavin-5-phosphate, and N-hydroxypyridine-2-(1H)-thione.  
     
     
         4 . The method of  claim 1 , wherein the at least one photosensitizer agent is Rose Bengal.  
     
     
         5 . The method of  claim 1 , wherein the contacting step occurs ex vivo.  
     
     
         6 . The method of  claim 1 , wherein the contacting step occurs in vivo in a subject.  
     
     
         7 . The method of  claim 6 , wherein the subject is a human.  
     
     
         8 . The method of  claim 1 , wherein the application of electromagnetic energy to the tissue-photosensitizer mixture occurs without substantial thermal tissue damage.  
     
     
         9 . The method of  claim 1 , wherein the application of electromagnetic energy to the tissue-photosensitizer mixture occurs without more than a 3° C. rise in temperature.  
     
     
         10 . The method of  claim 1 , wherein the application of electromagnetic energy to the tissue-photosensitizer mixture occurs without more than a 2° C. rise in temperature.  
     
     
         11 . The method of  claim 1 , wherein the application of electromagnetic energy to the tissue-photosensitizer mixture occurs without more than a 1° C. rise in temperature.  
     
     
         12 . A method for repairing a corneal lesion, comprising: 
 contacting a corneal tissue with at least one photosensitizer agent to form a corneal tissue-photosensitizer mixture; and    applying electromagnetic energy to the corneal tissue-photosensitizer mixture in a manner effective to elicit the production of a reactive species from the photosensitizer,    wherein the corneal tissue 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 corneal lesion.    
     
     
         13 . The method of  claim 12 , wherein the corneal lesion is caused by a surgical procedure.  
     
     
         14 . The method of  claim 13 , wherein the surgical procedure is selected from the group consisting of corneal transplant surgery, cataract surgery, laser surgery, keratoplasty, LASIK, refractive surgery, cornea reshaping, and treatment of corneal laceration.  
     
     
         15 . The method of  claim 12 , wherein the electromagnetic energy applied is greater than 200 J/cm 2 .  
     
     
         16 . The method of  claim 12 , wherein the electromagnetic energy is applied at an irradiance less than 3.5 W/cm 2 .  
     
     
         17 . A method for repairing a corneal lesion in vivo in a living subject, comprising: 
 contacting a corneal tissue with Rose Bengal (RB) to form a corneal tissue-RB mixture; and    applying electromagnetic energy to the corneal tissue-RB mixture in a manner effective to elicit the production of a reactive oxygen species from the RB,    wherein the corneal tissue 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 corneal lesion.    
     
     
         18 . The method of  claim 17 , wherein the subject is a human.  
     
     
         19 . The method of  claim 17 , wherein the corneal lesion is caused by a surgical procedure.  
     
     
         20 . The method of  claim 19 , wherein the surgical procedure is selected from the group consisting of corneal transplant surgery, cataract surgery, laser surgery, keratoplasty, LASIK, refractive surgery, cornea reshaping, and treatment of corneal laceration.  
     
     
         21 . A kit for repairing a corneal lesion comprising: 
 a photosensitizer agent; and    instructions for photoactivation of the photosensitizer agent to repair a corneal lesion.    
     
     
         22 . The kit of  claim 21 , wherein the photosensitizer agent is Rose Bengal.