Tissue decellularization

Abstract

The present invention relates, in general, to tissue decellularization and, in particular to a method of treating tissues, for example, heart valves, tendons and ligaments, so as to render them acellular and thereby limit mineralization and/or immunoreactivity upon implementation in vivo.

What is claimed is:  
     
         1 . A method of producing a decellularized tissue comprising: 
 i) contacting a biological tissue with a hypotonic solution under conditions such that lysis of cells of said tissue is effected, and    ii) contacting the tissue resulting from step (i) with nuclease under conditions such that nucleic acid is degraded,    said decellularized tissue thereby being produced.    
     
     
         2 . The method according to    claim 1    further comprising contacting the decellularized tissue with a physiologically isotonic solution.  
     
     
         3 . The method according to    claim 1    further comprising fixing said decellularized tissue.  
     
     
         4 . The method according to    claim 1    wherein said decellularized tissue is at least 70% decellularized.  
     
     
         5 . The method according to    claim 1    wherein the tissue is a mammalian tissue.  
     
     
         6 . The method according to    claim 1    wherein the tissue is a heart valve, tendon, ligament, artery, vein, diaphragm, pericardium, umbilical cord, facia, dura mater, tympanic membrane, or portion thereof.  
     
     
         7 . The method according to    claim 6    wherein said tissue is a heart valve.  
     
     
         8 . A decellularized tissue produced according to the method of    claim 1   .  
     
     
         9 . The tissue according to    claim 8    wherein said tissue is a heart valve, tendon, ligament, artery, vein, diaphragm, pericardium, umbilical cord, facia, dura mater, tympanic membrane, or portion thereof.  
     
     
         10 . The tissue according to    claim 9    wherein said tissue is a heart valve.  
     
     
         11 . The tissue according to    claim 8    wherein the tissue is at least 70% decellularized.  
     
     
         12 . The tissue according to    claim 8    wherein the tissue is fixed.  
     
     
         13 . A method of mitigating mineralization of a biological tissue transplant comprising: 
 i) contacting a biological tissue with a hypotonic solution under conditions such that lysis of cells of said biological tissue is effected, and    ii) contacting the tissue resulting from step (i) with nuclease under conditions such that nucleic acid is degraded,    wherein the tissue resulting from step (ii) is decellularized and said mitigation is thereby effected.    
     
     
         14 . The method according to    claim 13    wherein mineralization is mitigated by at least 30 percent relative to non-decellularized tissue.  
     
     
         15 . A method of reducing the immunogenicity of a biological tissue transplant comprising: 
 i) contacting a biological tissue with a hypotonic solution under conditions such that lysis of cells of said biological tissue is effected, and    ii) contacting the tissue resulting from step (i) with nuclease under conditions such that nucleic acid is degraded,    wherein the tissue resulting from step (ii) is decellularized and said reduction in immunogenicity is thereby effected.