The Cleveland Clinic Foundation

Aniq B Darr

Anthony Calabro

Richard A Gross

Kiyotaka Fukamachi

Keiji Kamohara

Anthony Miniaci

Hilel Lewis

Marshall Strome

Lee Akst

Daniel Alam

James Chan

David Haynes

Daniel P Knott

Alex Melamud

Michael K Banbury

Peter A Zahos

Firouz Daneshgari

A method is disclosed for treatment of urinary incontinence. The method includes the steps of providing to a person or animal, in the vicinity of a pubo-urethral ligament of the person or animal, a composition including collagen macromolecules that have hydroxyphenyl side groups substituted thereon, which are reacted to form dihydroxyphenyl linkages. In an embodiment, the collagen macromolecules are gelatin macromolecules. In another embodiment, the hydroxyphenyl side groups are tyramine side groups and the dihydroxyphenyl linkages are dityramine linkages. The composition can be injected into a space between a urethra and a pubis of the person or animal wherein the pubo-urethral ligament is disposed in the space. The method is advantageous, for example, based on being minimally invasive.

Methods to treat urinary incontinence

A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, particularly to provide a synthetic macromolecular network for a wide variety of tissue types. In particular, artificial or synthetic cartilage, vocal cord material, vitreous material, soft tissue material and mitral valve material are described. In an embodiment, the network is composed of tyramine-substituted and cross-linked hyaluronan molecules, wherein cross-linking is achieved via peroxidase-mediated dityramine-linkages that can be performed in vivo. The dityramine bonds provide a stable, coherent hyaluronan-based hydrogel with desired physical properties.

Hydroxyphenyl cross-linked macromolecular network and applications thereof

A synthetic nucleus pulposus is provided that is useful in treatment of degenerative disc disease, augmentation of a degenerate disc, and alleviation of back pain. In an embodiment the synthetic nucleus pulposus comprises hyaluronan macromolecules that have been cross-linked via dihydroxyphenyl linkages. The synthetic nucleus pulposus restores or improves the water-retention capability of the disc. A method of treating an intervertebral disc with the cross-linked hyaluronan macromolecules is also provided. A method of regenerative therapy to address loss of cells of nucleus pulposus of an intervertebral disc based on treatment with the cross-linked hyaluronan macromolecules and mesenchymal stem cells is also provided.

A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, particularly to provide a synthetic, implantable tissue matrix material for a wide variety of tissue types. In particular, artificial or synthetic cartilage, vocal cord material, vitreous material, soft tissue material and mitral valve material are described. In an embodiment, the network is composed of tyramine-substituted and cross-linked hyaluronan molecules, wherein cross-linking is achieved via peroxidase-mediated dityramine-linkages that can be performed in vivo. The dityramine bonds provide a stable, coherent hyaluronan-based hydrogel with desired physical properties.

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.

Growing community of inventors

Parma Heights, OH, United States of America

Aniq B Darr