Calcification-resistant biomaterials
First Claim
1. A bioprosthetic article comprising a biocompatible material forming at least a portion of said bioprosthetic article and a plurality of exogenous storage structures that are bound to the biocompatible material by covalent bonds, antibody-antigen associations, specific binding protein-receptor associations or enzyme-substrate associations, said exogenous storage structures comprising natural macromolecules selected from the group consisting of proteins, carbohydrates and nucleic acids that are in addition or as an alternative to any naturally occurring structures and said exogenous storage structures collectively having greater than about 0.5 mg metal cations per gram of biocompatible material releasably bound thereto.
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Abstract
The invention involves a bioprosthetic article including a biocompatible material having at least one bound exogenous storage structure, the storage structures having collectively greater than about 0.5 mg metal cations per gram of biocompatible material. The calcification inhibitors preferably decrease calcium deposition by greater than 95% relative to untreated tissue. The calcification inhibitors are bonded to the bioprosthetic material preferably at a pH between about 6.0 and 8.5.
47 Citations
24 Claims
- 1. A bioprosthetic article comprising a biocompatible material forming at least a portion of said bioprosthetic article and a plurality of exogenous storage structures that are bound to the biocompatible material by covalent bonds, antibody-antigen associations, specific binding protein-receptor associations or enzyme-substrate associations, said exogenous storage structures comprising natural macromolecules selected from the group consisting of proteins, carbohydrates and nucleic acids that are in addition or as an alternative to any naturally occurring structures and said exogenous storage structures collectively having greater than about 0.5 mg metal cations per gram of biocompatible material releasably bound thereto.
- 12. A bioprosthetic article comprising natural tissue and a plurality of exogenous storage structures that are bound to said natural tissue by covalent bonds, antibody-antigen associations, specific binding protein-receptor associations or enzyme-substrate associations, said storage structures comprising natural macromolecules selected from the group consisting of proteins, carbohydrates and nucleic acids that are in addition or as an alternative to any naturally occurring structures, said storage structures having a quantity of calcification inhibitors releasably bound thereto, and said natural tissue having calcium deposition reduced by greater than about 95 percent relative to equivalent natural tissue without said bound exogenous storage structures after approximately two months of subcutaneous implantation within a mammal.
- 16. A method of producing a bioprosthetic article comprising the step of binding ferritin to natural tissue, where said ferritin is loaded with calcification inhibiting metal cations such that there are at least 0.5 mg of metal cations per gram of said natural tissue.
Specification