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 forming a coating on a surface of a vascular stent, the coating imparting improved biocompatibility characteristics to the surface, the surface being suitable for contacting tissue or blood, the method comprising: (a) providing the vascular stent; (b) providing a peptide having at least one anti-inflammatory property; and (c) combining the anti-inflammatory peptide with a polymer comprising a polyethylene to form a coating, the coating immobilizing the anti-inflammatory peptide on the surface.  
     
     
         36 . The method of  claim 35  wherein the anti-inflammatory peptide is a naturally occurring peptide.  
     
     
         37 . The method of  claim 35  wherein the anti-inflammatory peptide is a chemically synthesized peptide.  
     
     
         38 . The method of  claim 35  wherein the vascular stent is suitable for implantation in a blood vessel.  
     
     
         39 . The method of  claim 35  wherein the immobilized anti-inflammatory peptide minimizes at least one adverse biological reaction.  
     
     
         40 . The method of  claim 35  wherein the vascular stent is tubular in shape.  
     
     
         41 . The method of  claim 35  wherein at least a portion of the surface forms a tube.  
     
     
         42 . The method of  claim 35  wherein the vascular stent comprises a metal.  
     
     
         43 . The method of  claim 42  wherein the metal is a stainless steel.  
     
     
         44 . The method of  claim 42  wherein the metal is a titanium alloy.  
     
     
         45 . The method of  claim 42  wherein the metal is a shape memory alloy.  
     
     
         46 . The method of  claim 42  wherein the metal is a platinum alloy.  
     
     
         47 . The method of  claim 42  wherein the metal is MP35N.  
     
     
         48 . The method of  claim 42  wherein the metal is TiNi.  
     
     
         49 . The method of  claim 35  further comprising the step of combining at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane.  
     
     
         50 . The method of  claim 35  further comprising the step of combining a chemical moiety of the anti-inflammatory peptide with a chemical moiety of the polyethylene polymer to form a chemical bond.  
     
     
         51 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is an aldehyde moiety.  
     
     
         52 . The method of  claim 51  wherein the aldehyde moiety is formed by combining a periodate with a 2-aminoalcohol moiety.  
     
     
         53 . The method of  claim 52  wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.  
     
     
         54 . The method of  claim 51  wherein the aldehyde moiety is formed by combining a periodate with a 1,2-dihydroxy moiety.  
     
     
         55 . The method of  claim 54  wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.  
     
     
         56 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is an epoxide moiety.  
     
     
         57 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is an isocyanate moiety.  
     
     
         58 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is a 1,2-dicarbonyl moiety.  
     
     
         59 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is a phosphate moiety.  
     
     
         60 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is a sulphate moiety.  
     
     
         61 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is a carboxylate moiety.  
     
     
         62 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is a guanidino moiety.  
     
     
         63 . The method of  claim 62  wherein the guanidino moiety is formed by combining an amine moiety with a guanidino forming agent.  
     
     
         64 . The method of  claim 63  wherein the guanidino forming agent is selected from the group consisting of S-ethylthiouronium bromide, S-ethylthiouronium chloride, O-methylisourea, O-methylisouronium sulfate, O-methylisourea hydrogen sulfate, S-methylisothiourea, 2-methyl-1-nitroisourea, aminoiminomethanesulfonic acid, cyanamide, cyanoguanide, dicyandiamide, 3,5-dimethyl-1-guanylpyrazole nitrate and 3,5-dimethyl pyrazole.  
     
     
         65 . The method of  claim 63  further comprising the step of combining a stabilizing agent.  
     
     
         66 . The method of  claim 65  wherein the stabilizing agent is a borate ion.  
     
     
         67 . The method of  claim 63  wherein the amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.  
     
     
         68 . The method of  claim 67  wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.  
     
     
         69 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is a primary amine moiety.  
     
     
         70 . The method of  claim 69  wherein the primary amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.  
     
     
         71 . The method of  claim 70  wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.  
     
     
         72 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is an aldehyde moiety.  
     
     
         73 . The method of  claim 72  wherein the aldehyde moiety is formed by combining a periodate with a 2-aminoalcohol moiety.  
     
     
         74 . The method of  claim 73  wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.  
     
     
         75 . The method of  claim 72  wherein the aldehyde moiety is formed by combining a periodate with a 1,2-dihydroxy moiety.  
     
     
         76 . The method of  claim 75  wherein the periodate comprises at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate.  
     
     
         77 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is an epoxide moiety.  
     
     
         78 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is an isocyanate moiety.  
     
     
         79 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is a 1,2-dicarbonyl moiety.  
     
     
         80 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is a phosphate moiety.  
     
     
         81 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is a sulphate moiety.  
     
     
         82 . The method of  claim 50  wherein the chemical moiety of the polyethylene polymer is a carboxylate moiety.  
     
     
         83 . The method of  claim 50  wherein the chemical moiety of the anti-inflammatory peptide is a guanidino moiety.  
     
     
         84 . The method of  claim 83  wherein the guanidino moiety is formed by combining an amine moiety with a guanidino forming agent.  
     
     
         85 . The method of  claim 84  wherein the guanidino forming agent is selected from the group consisting of S-ethylthiouronium bromide, S-ethylthiouronium chloride, O-methylisourea, O-methylisouronium sulfate, O-methylisourea hydrogen sulfate, S-methylisothiourea, 2-methyl-1-nitroisourea, aminoiminomethanesulfonic acid, cyanamide, cyanoguanide, dicyandiamide,  3 ,5-dimethyl-1-guanylpyrazole nitrate and  3 ,5-dimethyl pyrazole.  
     
     
         86 . The method of  claim 84  further comprising the step of combining a stabilizing agent.  
     
     
         87 . The method of  claim 86  wherein the stabilizing agent is a borate ion.  
     
     
         88 . The method of  claim 84  wherein the amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.  
     
     
         89 . The method of  claim 88  wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.  
     
     
         90 . The method of  claim 50  wherein the chemical moiety of the anti- inflammatory peptide is a primary amine moiety.  
     
     
         91 . The method of  claim 90  wherein the primary amine moiety is formed by combining an unsubstituted amide moiety with an amine forming agent.  
     
     
         92 . The method of  claim 91  wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.  
     
     
         93 . The method of  claim 35  wherein the vascular stent comprises the polyethylene polymer.  
     
     
         94 . The method of  claim 35  wherein the surface comprises the polyethylene polymer.  
     
     
         95 . The method of  claim 35  wherein the polyethylene polymer is coated on the vascular stent.  
     
     
         96 . A method for improving the biocompatibility characteristics of a vascular stent, the method comprising the steps of: (a) providing the stent; (b) providing a biomolecule, the biomolecule comprising an anti-inflammatory peptide; and (c) combining a chemical moiety of the biomolecule with a chemical moiety of a biomaterial to form a coating, the biomaterial comprising a polyethylene, the coating immobilizing the biomolecule on a surface of the stent.  
     
     
         97 . The method of  claim 96  wherein the biomolecule is a naturally occurring biomolecule.  
     
     
         98 . The method of  claim 96  wherein the biomolecule is a chemically synthesized biomolecule.  
     
     
         99 . A vascular stent comprising a biomaterial and a coating comprising an immobilized biomolecule, the biomolecule comprising a peptide, the peptide being an anti-inflammatory, the coating comprising the combination of the biomolecule with the biomaterial, the biomaterial comprising a polyethylene, the coating capable of minimizing at least one adverse biological reaction.  
     
     
         100 . A stent suitable for implantation in a blood vessel having a biomolecule immobilized on a surface to minimize at least one adverse biological reaction, the biomolecule comprising an anti-inflammatory peptide, the stent comprising a coating formed from a biomaterial binding with the biomolecule, the biomaterial comprising a polyethylene, the coating immobilizing the biomolecule on the surface.  
     
     
         101 . A method of immobilizing a biomolecule on a surface of a tubular vascular stent, the biomolecule comprising a peptide, the peptide having at least one ant-inflammatory property, the biomolecule imparting improved biocompatibility characteristics to the surface, the surface being suitable for contacting tissue or blood, the method comprising the step of chemically combining the biomolecule with a polymer to immobilize the biomolecule on the surface, the polymer comprising a polyethylene, the resultant stent comprising the biomolecule in combination with the polymer.  
     
     
         102 . A method for improving the biocompatibility characteristics of a vascular stent, the method comprising the steps of: (a) providing the stent; (b) providing a biomolecule, the biomolecule comprising an anti-inflammatory peptide; and (c) combining a chemical moiety of the biomolecule with a chemical moiety of a biomaterial to form a coating, the biomaterial comprising a polyacrylate, the coating immobilizing the biomolecule on a surface of the stent.  
     
     
         103 . A method for improving the biocompatibility characteristics of a vascular stent, the method comprising the steps of: (a) providing the stent; (b) providing a biomolecule, the biomolecule comprising an anti-inflammatory peptide; and (c) combining a chemical moiety of the biomolecule with a chemical moiety of a biomaterial to form a coating, the biomaterial comprising a polyolefin, the coating immobilizing the biomolecule on a surface of the stent.