HYDROXYPHENYL CROSS-LINKED MACROMOLECULAR NETWORK AND APPLICATIONS THEREOF

Application 1504/KOLNP/2005 published 2006-07-14, filed 2005-08-01
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. (FIG). 2

Applicant

THE CLEVELAND CLINIC FOUNDATION.,
9500 EUCLID AVENUE, CLEVELAND, OH 44195, USA.

Inventor

CALABRO, ANTHONY GROSS, RICHARD, A DARR, ANIQ, B

International Info

Classification: C08G 63/48, 63/81, C08L 71/00, C12Q 1/00
Publication Number: WO 04/063388
Application Date: 2004-01-09

Priority Information

60/439,201 USA 2003-01-10