Method for using tropoelastin and for producing tropoelastin biomaterials

Abstract

It is a general object of the invention to provide a method of effecting repair or replacement or supporting a section of a body tissue using tropoelastin, preferably crosslinked tropoelastin and specifically to provide a tropoelastin biomaterial suitable for use as a stent, for example, a vascular stent, or as conduit replacement, as an artery, vein or a ureter replacement. The tropoelastin biomaterial itself can also be used as a stent or conduit covering or coating or lining.

1 . A method for producing a tissue substrate fusible biomaterial consisting essentially of tropoelastin which is fusible to a tissue substrate comprising: 
 providing a polymerizable monomer consisting essentially of tropoelastin;    polymerizing said polymerizable monomer to form a polymer consisting essentially of tropoelastin:    forming a layer of said biomaterial from said tropoelastin polymer having a first and second outer major surface; and    applying an energy absorbing material, which is energy absorptive within a predetermined range of light wavelengths, to a selected one of said first and second outer surfaces of the biomaterial in an amount which will cause fusing together of one of said first and second outer surfaces of the biomaterial and one of said first and second outer surfaces of said tissue substrate, said energy absorbing material penetrating into the interstices of said biomaterial; and    irradiating the energy absorbing material with light energy in said predetermined wavelength range with an intensity sufficient to fuse together one of said first and second outer surfaces of the biomaterial and the tissue substrate.    
     
     
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         11 . The method of  claim 1 , wherein the tissue substrate is a live tissue substrate.  
     
     
         12 . The method of  claim 1 , wherein the average thickness of the energy absorbing material which penetrates into the interstices of the biomaterial is from about 0.5 to 300 microns.  
     
     
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         14 . The method of  claim 1 , wherein the tissue substrate is selected from a group consisting of bladders, intestines, tubes, esophagus, ureters, arteries, veins, stomachs, lungs, hearts, colons, and skin.  
     
     
         15 . The method of  claim 1 , wherein said polymerizable monomer consists essentially of non-mammalian tropoelastin.  
     
     
         16 . The method of  claim 15 , wherein said non-mammalian tropoelastin consists essentially of recombinant tropoelastin.  
     
     
         17 . The method of  claim 15 , wherein said recombinant tropoelastin is produced by a protein expression system.  
     
     
         18 . The method of  claim 1 , which further includes the step of forming a cellular lining of human cells on one of the major surfaces of said biomaterial layer.  
     
     
         19 . The method of  claim 18 , wherein said cells which are employed to form said cellular lining are at least one of endothelial cells, epithelial cells and urothelial cells.  
     
     
         20 . The method of  claim 1 , which further includes the step of forming an inner lining consisting essentially of tropoelastin for mechanical human structures to ensure their continued internal use in a human body.  
     
     
         21 . The method of  claim 20 , which further includes the step of forming said inner lining in heart valves, heart implants, dialysis equipment, or oxygenator tubing for heart-lung by-pass systems.  
     
     
         22 . The method of  claim 1 , which includes the step of introducing a drug into said biomaterial.  
     
     
         23 . A method for producing a prosthetic device comprising: 
 providing a polymerizable monomer consisting essentially of tropoelastin;    polymerizing said polymerizable monomer to form a polymer consisting essentially of tropoelastin:    forming a layer of said biomaterial from said tropoelastin polymer having a first and second outer major surface;    providing a support member comprising a stent, a conduit or a scaffold; and    applying said layer of said biomaterial to said support member to form said prosthetic device.    
     
     
         24 . The method of  claim 23 , which includes the step of applying the layer of said biomaterial so that it surrounds said support member.  
     
     
         25 . The method of  claim 23 , which includes the step of forming said biomaterial by polymerization.  
     
     
         26 . The method of  claim 23 , which includes the step of molding said biomaterial of a suitable size and shape.  
     
     
         27 . The method of  claim 23 , which includes the step of forming said biomaterial into a sheet or tube, and then covering said support member with said sheet or tube.  
     
     
         28 . The method of  claim 23 , which includes the step of applying said biomaterial layer to said support by grafting.  
     
     
         29 . The method of  claim 23 , which includes the step of applying said biomaterial layer to said support by mechanical bonding.  
     
     
         30 . The method of  claim 23 , which includes the step of applying said biomaterial layer to said support by laser bonding.  
     
     
         31 . The method of  claim 23 , which includes the step of incorporating a drug into said biomaterial layer thereby decreasing the need for systemic intravenous or oral medications.  
     
     
         32 . The method of  claim 23 , wherein said support member comprises titanium, tantalum, stainless steel or nitinol.  
     
     
         33 . The method of  claim 23 , wherein said polymerizable monomer consists essentially of non-mammalian tropoelastin.  
     
     
         34 . The method of  claim 33 , wherein said non-mammalian tropoelastin consists essentially of recombinant tropoelastin.  
     
     
         35 . The method of  claim 34 , wherein said recombinant tropoelastin is produced by a protein expression system.  
     
     
         36 . A method for producing a biomaterial, which comprises: 
 providing a polymerizable monomer consisting essentially of non-mammalian tropoelastin;    polymerizing said polymerizable monomer to form a polymer consisting essentially of non-mammalian tropoelastin; and    forming a biomaterial consisting essentially of non-mammalian tropoelastin from said polymer.    
     
     
         37 . The method of  claim 36 , wherein said non-mammalian tropoelastin consists essentially of recombinant tropoelastin.  
     
     
         38 . The method of  claim 37 , wherein said recombinant tropoelastin is produced by a protein expression system.  
     
     
         39 . A method for producing a biomaterial, which comprises: 
 providing a crosslinkable monomer consisting essentially of tropoelastin;    crosslinking said crosslinkable monomer to form a crosslinked polymer consisting essentially of crosslinked tropoelastin; and    forming a biomaterial from said crosslinked polymer consisting essentially of crosslinked tropoelastin.    
     
     
         40 . The method of  claim 39 , wherein said crosslinked tropoelastin consists essentially of tropoelastin having non-naturally occurring cross-links.  
     
     
         41 . The method of  claim 39 , wherein said crosslinked tropoelastin consists essentially of chemically crosslinked tropoelastin having non-naturally occurring chemical cross-links.  
     
     
         42 . The method of  claim 41 , wherein said chemically crosslinked tropoelastin having non-naturally occurring chemical cross-links is crosslinked using glutaraldelhyde as the crosslinking agent.  
     
     
         43 . The method of  claim 39 , wherein said crosslinked polymer consists essentially of crosslinked recombinant tropoelastin.  
     
     
         44 . The method of  claim 39 , wherein said crosslinked tropoelastin consists essentially of enzymatically crosslinked tropoelastin having non-naturally occurring enzymatic cross-links.  
     
     
         45 . The method of  claim 39 , wherein said crosslinked tropoelastin consists essentially of radiatively crosslinked tropoelastin having non-naturally occurring irradiated cross-links.  
     
     
         46 . The method of  claim 45 , wherein said crosslinked tropoelastin consists essentially of radiatively crosslinked tropoelastin having non-naturally occurring γ-irradiated crosslinks.  
     
     
         47 . The method of  claim 46 , wherein said -y-irradiated cross-links are produced by free radicals which result in crosslink formation.  
     
     
         48 . The method of  claim 39 , which further includes organizing the crosslinkable tropoelastin monomer prior to the cross-linking step.  
     
     
         49 . The method of  claim 48 , wherein organizing the crosslinkable tropoelastin monomer prior to the cross-linking step comprises coacervation.  
     
     
         50 . The method of  claim 39 , wherein the crosslinkable tropoelastin monomer is combined with collagen and then crosslinked to form a crosslinked tropoelastin-collagen composite.