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.