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.