The Cleveland Clinic Foundation

Other

Anthony Calabro

Aniq B Darr

Richard A Gross

Kiyotaka Fukamachi

Keiji Kamohara

Kathleen Anne Derwin

Anthony Miniaci

Hilel Lewis

Marshall Strome

Vincent Hascall

Daniel P Knott

Alex Melamud

Lee Akst

Daniel Alam

James Chan

Mark Lauer

David Haynes

Joseph P Iannotti

Michael K Banbury

Peter A Zahos

Firouz Daneshgari

LiKang Chin

Joseph Patrick Iannotti

Biocompatible tissue grafts are provided. The biocompatible tissue grafts include a bulk graft including a biocompatible material and having at least a first surface. The biocompatible tissue grafts also include a coating including a hydrogel and being immobilized on the bulk graft at the first surface. The biocompatible material includes at least one of a biologic material or a biologic-synthetic composite material. The hydrogel includes cross-linked hydroxyphenyl-substituted hyaluronan (HPS-HA), cross-linked hydroxyphenyl-substituted collagen (HPS-C), or both. The cross-linked HPS-HA, cross-linked HPS-C, or both have been formed by cross-linking of hydroxyphenyl groups of HPS-HA, HPS-C, or both to form dihydroxyphenyl bridges. Also disclosed are methods for repair of tissue damage in a subject in need thereof. The methods include surgically implanting the biocompatible tissue graft into a site of the tissue damage in the subject.

Biocompatible tissue graft

Pharmaceutical compositions are provided. The compositions comprise a compound comprising the hyaluronan-containing structure A-(low molecular weight hyaluronan domain)-B. The compositions also comprise a pharmaceutically acceptable excipient. A is hydrogen, a substituent that does not comprise a binding site for tumor necrosis factor stimulated gene-6 ('TSG-6') protein, a substituent that interferes with binding of TSG-6 protein immediately adjacent thereto, or chondroitin. B is hydroxyl, a substituent that does not comprise a binding site for TSG-6 protein, a substituent that interferes with binding of TSG-6 protein immediately adjacent thereto, or chondroitin. The composition is suitable for administration by injection, inhalation, topical rub, or ingestion. Also disclosed are methods and kits for treating a site of inflammation in an individual in need thereof and for decreasing heavy chain modification of pathological hyaluronan at a site of inflammation in an individual in need thereof based on administering the compounds or the compositions.

Treatment of extracellular matrix to reduce inflammation

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 composition comprising a human- or animal-derived extracellular matrix and a macromolecular network which is prepared ex vivo is provided that is useful in the repair of a tissue injury, particularly in repair of tears or gaps between a tendon and a bone, such as in a rotator cuff tear. In an embodiment, the composition comprises a human- or animal-derived extracellular matrix having impregnated therein a macromolecular network of hyaluronan macromolecules that have been cross-linked via dihydroxyphenyl linkages, so that the cross-linked network is interlocked within the extracellular matrix. The resulting HA-incorporated extracellular matrix can be supplied in the form of a patch to reinforce a tissue repair or cover a tissue defect.

Molecular enhancement of extracellular matrix and methods of use

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.

An adjustable ear clip device for relieving pressure on the ear lobe of a wearer is provided. The adjustable ear clip includes a base plate with a pair of spaced ears connected thereto. An angled stop plate emanates from the base plate at a location adjacent to the bottom of a notch in the base plate. A mounting plate is connected to the base plate to receive an ornamental member. An ear engaging member includes a pair of spring-biased arms for engaging the ears. A spring tongue is positioned between the arms and has a stop bolt aperture therethrough. A stop bolt is threaded through the spring tongue and engages with the angled stop plate to limit the travel of the ear engaging member toward the ornamental member.

Adjustable ear clip

A removable and yieldable hood ornament apparatus which includes a compact structure for easy transportability is disclosed. The apparatus includes a base member with an ornament emblem mounted thereto, the base member includes a plurality of transversely protruding key members for receipt by a plurality of locking members positioned within a housing disposed below the surface of the automobile hood. A spring biased floor maintains the protruding key members in their respective locking members. The short base member is inserted into the housing below the hood of the automobile against the forces of the spring and then rotated along its longitudinal axis to effect locking. The forces of the spring maintain the apparatus in a locked condition.

Removable hood ornament

An ear clip is disclosed that includes a jaw hinged to a base member to which an ornament may be affixed. The jaw is provided with a spring tongue that engages the base member and normally urges the jaw in one direction. The end of the spring tongue is provided with a plurality of notches and the end portion is bent from a plane of the jaw at an obtuse angle to insure positive engagement of the base member with the notches. Additional depressions on the inner face of mounting or pivot ears may be provided for additional positive adjustable engagement.

Growing community of inventors

Cleveland Heights, OH, United States of America

Anthony Calabro