Method for Attachment of Biomolecules to Medical Device Surfaces

Abstract

A method for making a medical device having at least one biomolecule immobilized on a substrate surface is provided. One method of the present invention includes immobilizing a biomolecule comprising an unsubstituted amide moiety on a biomaterial surface. Another method of the present invention includes immobilizing a biomolecule on a biomaterial surface comprising an unsubstituted amide moiety. Still another method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties immobilized on medical device surfaces. Additionally, one method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties in solution, thereby forming a crosslinked biomaterial or a crosslinked medical device coating.

1 - 34 . (canceled) 
     
     
         35 . A method of coating a tissue heart valve comprising an amine functional moiety comprising contacting the heart valve with a peptide biomolecule a comprising an aldehyde moiety; wherein the amine and aldehyde form a covalent chemical bond and, thereby immobilizing the biomolecule on the heart valve and forming the coating. 
     
     
         36 . The method of  claim 35  wherein the aldehyde moiety is prepared by contacting the biomolecule with periodate. 
     
     
         37 . The method of  claim 35  wherein the biomolecule is a naturally occurring biomolecule. 
     
     
         38 . The method of  claim 35  wherein the biomolecule is a chemically synthesized biomolecule. 
     
     
         39 . The method of  claim 35  wherein the biomolecule is a protein. 
     
     
         40 . The method of  claim 39  wherein the protein is fibrinogen, fibronectin, collagen or vitronectin. 
     
     
         41 . The method of  claim 40  wherein the protein is fibronectin. 
     
     
         42 . The method of  claim 40  wherein the protein is fibrinogen. 
     
     
         43 . The method of  claim 36  wherein a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety present on the biomolecule is reacted with the periodate to provide the aldehyde moiety. 
     
     
         44 . The method of  claim 35  wherein the amine functional moiety on the heart valve is a primary amine moiety. 
     
     
         45 . The method of  claim 35  wherein the biomolecule comprises an arginine-glycine-aspartic acid sequence. 
     
     
         46 . A method of coating a tissue heart valve comprising an aldehyde moiety comprising contacting the heart valve with a peptide biomolecule a comprising an amine functional moiety; wherein the amine and aldehyde form a covalent chemical bond and, thereby immobilizing the biomolecule on the heart valve and forming the coating. 
     
     
         47 . The method of  claim 46  wherein the biomolecule is a naturally occurring biomolecule. 
     
     
         48 . The method of  claim 46  wherein the biomolecule is a chemically synthesized biomolecule. 
     
     
         49 . The method of  claim 46  wherein the biomolecule is a protein. 
     
     
         50 . The method of  claim 49  wherein the protein is fibrinogen, fibronectin, collagen or vitronectin. 
     
     
         51 . The method of  claim 50  wherein the protein is fibronectin. 
     
     
         52 . The method of  claim 50  wherein the protein is fibrinogen. 
     
     
         53 . The method of  claim 46  wherein the amine functional moiety on the biomolecule is a primary amine moiety. 
     
     
         54 . The method of  claim 46  wherein the biomolecule comprises an arginine-glycine-aspartic acid sequence.