Method for attachment of biomolecules to medical device surfaces

A method of forming a coating on a surface of a medical device, the method comprising the steps of:

• (a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety;
• (b) combining the amide moiety with an amine forming agent to form an amine-functional surface;
• (c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface;
• (d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety, and a carboxylate moiety;
• and
• (e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.

A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of:

• (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety;
• (b) combining the amide moiety with an amine forming agent to form an amine-functional surface;
• (c) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an epoxide moiety and an isocyanate moiety;
• and
• (d) combining the chemical moiety with the surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.

A method of forming a crosslinked coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of:

• (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising unsubstituted amide moieties:
• (b) combining the amide moieties with an amine forming agent to form amine moieties;
• (c) providing biomolecules having at least one chemically reactive moiety selected from the group consisting of a 1,2-dihydroxy moiety and a 2-aminoalcohol moiety, combining periodate with the biomolecules to oxidize the chemically reactive moiety to form aldehyde moieties;
• (d) combining the biomolecules with the surface;
• (e) allowing the aldehyde moieties to combine with the amine moieties to form imine moieties;
• and
• (f) reacting the imine moieties with a reducing agent to form amine linkages, the amine linkages immobilizing and crosslinking the biomolecules on the surface, the immobilized and crosslinked biomolecules forming the coating.

A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of:

• (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety;
• (b) combining the amide moiety with an amine forming agent 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 to form an amine-functional surface;
• (c) providing a biomolecule, the biomolecule comprising a 2-aminoalcohol moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 2-aminoalcohol moiety to form an aldehyde moiety;
• (d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety;
• and
• (e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.

A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of:

• (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety;
• (b) combining the amide moiety with an amine forming agent 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 to form an amine-functional surface;
• (c) providing a biomolecule, the biomolecule comprising a 1,2-dihydroxy moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 1,2-dihydroxy moiety to form an aldehyde moiety;
• (d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety;
• and
• (e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.