Barnes Jewish Hospital

Isto Technologies, Inc.

Huston Davis Adkisson

Curt L Milliman

Neil Kizer

Michael J Maloney

Michael O Maloney

Gary B Gage

Nicole M Bergmann

The present disclosure relates to cartilage repair compositions and methods for modifying the proteoglycan content of the compositions. Specifically, the methods relate to serum free, collagen free neocartilage made from chondrocytes that can be used for implants. Proteoglycans, such as aggrecan and sulfated glycosaminoglycan are used and the content modified using temperature changes.

Neocartilage compositions and methods for modifying proteoglycan content

The present invention provides a method for expanding a population of chondrocytes that maintains chondrocyte phenotype during the expansion by culturing the population in a defined serum-free expansion medium containing one or more cytokines and under low attachment conditions. The method further solves diffusion problems during the subsequent stage of extracellular matrix production by use of a perforated polycarbonate substrate that results in a randomly organized cultured neocartilage tissue. Chondrocytes expanded and cultured in this manner can be used in various medical applications to repair cartilaginous tissues that have been injured by trauma or disease.

Method for chondrocyte expansion with phenotype retention

The present invention provides a method that maintains chondrocyte phenotype during serial expansion by culturing a population of chondrocytes in a defined serum-free culture medium containing cytokines and on a substrate that is modified by covalent attachment of hyaluronic acid. The underlying principle is to maintain native chondrocyte phenotype by growing the dissociated chondrocytes on a substrate modified by covalent attachment of hyaluronic acid to retain native chondrocyte morphology and function. Chondrocyte expanded in this manner can be used in various medical applications to repair cartilaginous tissues that have been injured by trauma or disease. This substratum provides a microenvironment that more closely mimics that of native articular cartilage, thereby promoting chondrogenesis in a predictable manner.

Disclosed are neocartilage compositions characterized by having multiple layers of cells, said cells being surrounded by a substantially continuous insoluble glycosaminoglycan and collagen-enriched hyaline extra-cellular matrix, and which neocartilage phospholipids are advantageously enriched in anti-inflammatory n-9 fatty acids, particularly 20:3 n-9 eicosatrienoic or Mead acid. Also disclosed are methods of growing neocartilage in substantially serum-free growth media and methods of producing a conditioned growth media containing compounds effective to enhance neocartilage formation. The neocartilage compositions are useful as implants and as replacement tissue for damaged or defective cartilage and as a model system for studying articular cartilage disease and response to natural and synthetic compounds.

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St. Louis, MO, United States of America

Huston Davis Adkisson