Hydroxyphenyl cross-linked macromolecular network and applications thereof
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Abstract
A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, such as artificial or synthetic cartilage. The network is made by first providing a polyamine or polycarboxylate macromolecule (having a plurality of amine or carboxylic acid groups respectively attached along the length of the molecule), reacting this macromolecule with a hydroxyphenyl compound having a free carboxylic acid group in the case of a polyamine or a free primary amine group in the case of a polycarboxylate, and substituting the hydroxyphenyl compound onto the macromolecule via a carbodiimide-mediated reaction pathway to provide a hydroxyphenyl-substituted macromolecule. This macromolecule is then linked to other such macromolecules via an enzyme catalyzed dimerization reaction between two hydroxyphenyl groups attached respectively to different macromolecules under metabolic conditions of temperature and pH. In a preferred embodiment, the macromolecular network is made up of tyramine-substituted hyaluronan molecules that are linked by dityramine bonds to provide a stable, coherent hydrogel with desired physical properties. A method of preparing such a network is also provided.
27 Citations
65 Claims
- 1. A macromolecular network comprising
- 25. A macromolecular network comprising a plurality of tyramine-substituted hyaluronan molecules, at least two adjacent hyaluronan molecules being linked by a dityramine linkage.
- 30. A hydrogel comprising a macromolecular network of tyramine-substituted hyaluronan molecules that are cross-linked by dityramine linkages between hyaluronan molecules.
- 39. A method of making a macromolecular network comprising the steps of providing a first macromolecular species selected from the group consisting of hydroxyphenyl-substituted polycarboxylates, hydroxyphenyl-substituted polyamines, other polyhydroxyphenyl molecules, and copolymers thereof, and forming at least one dihydroxyphenyl linkage between two hydroxyphenyl groups attached respectively to adjacent ones of said first macromolecular species.
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55. A method of making a hydrogel comprising the steps of:
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a) providing a first solution comprising either a peroxidase enzyme or a peroxide but not both, and also a macromolecular species selected from the group consisting of hydroxyphenyl-substituted polycarboxylates, hydroxyphenyl-substituted polyamines, other polyhydroxyphenyl molecules, and copolymers thereof;
b) providing a second solution comprising the one of said peroxidase enzyme or peroxide not provided in said first solution; and
c) combining said first and second solutions to initiate dihydroxyphenyl cross-linking to form said hydrogel. - View Dependent Claims (56, 57, 58, 59, 60, 61, 62, 63, 64, 65)
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Specification