A cryopreserved cartilage product is disclosed. The cryopreserved cartilage product can include a partially digested cryopreserved natural cartilage collagen matrix isolated from a subject. The collagen matrix can include viable cells embedded within the collagen matrix that are native to the collagen matrix and that were embedded in the collagen matrix when the collagen matrix was isolated from the subject, at least 70% of the embedded cells native to the collagen matrix can be viable in the cryopreserved cartilage product, and the partially digested collagen matrix can retain interaction between the collagen matrix and the native cells.

A bioprinter comprises one or more dispensing units. Each dispensing unit may include (i) a syringe including a hollow body and a plunger dimensioned to translate in the body wherein the body has an exit orifice; (ii) an actuator in contact with a proximal end of the plunger; (iii) a controller for moving the actuator; and (iv) a nozzle having a wall defining a fluid path extending from an inlet of the nozzle to an outlet of the nozzle. The inlet of the nozzle is in fluid communication with the exit orifice of the syringe body. The nozzle includes a fluid passageway in fluid communication with a source of fluid and the fluid path. The bioprinter can be used in a method of preparing microtissue comprising dispensing a bioink from one or more dispensing units of the bioprinter on a plate. The microtissue may comprise cartilage cells or tumor cells or liver cells.

Provided is a cell sheet suitable for cartilage repair. The present invention provides a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the cell sheet is negative for immunostaining using an antibody against type II collagen. The present invention also provides a method for producing a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the method includes culturing cells derived from a cartilage tissue on a surface of a membrane, where a temperature-responsive polymer is immobilized on the surface, to give the cell sheet. The culturing is stopped before the cell sheet becomes positive for immunostaining using an antibody against type II collagen.

This invention provides disrupted cartilage products, methods of manufacturing disrupted cartilage products, and methods of treating a subject comprising administering a cartilage product. The cartilage products are manufactured by a method comprising disrupting a collagen matrix, e.g. to produce a flexible cartilage product. Optionally, the cartilage products comprise viable chondrocytes, bioactive factors such as chondrogenic factors, and a collagen type II matrix. Optionally, the cartilage products are non-immunogenic.

This invention provides porated cartilage products and methods of producing porated cartilage products. Optionally, the cartilage products are sized, porated, and digested to provide a flexible cartilage product. Optionally, the cartilage products comprise viable chondrocytes, bioactive factors such as chondrogenic factors, and a collagen type II matrix. Optionally, the cartilage products are non-immunogenic.

A method of modulating transdifferentiation of chondrocytes to osteoblast includes administering to the chondrocytes an agent that modulates GP130 receptor signaling and expression of at least one of Sox2, Oct4, or Nanog of the chondrocytes.

A bioprinter comprises one or more dispensing units. Each dispensing unit may include (i) a syringe including a hollow body and a plunger dimensioned to translate in the body wherein the body has an exit orifice; (ii) an actuator in contact with a proximal end of the plunger; (iii) a controller for moving the actuator; and (iv) a nozzle having a wall defining a fluid path extending from an inlet of the nozzle to an outlet of the nozzle. The inlet of the nozzle is in fluid communication with the exit orifice of the syringe body. The nozzle includes a fluid passageway in fluid communication with a source of fluid and the fluid path. The bioprinter can be used in a method of preparing microtissue comprising dispensing a bioink from one or more dispensing units of the bioprinter on a plate. The microtissue may comprise cartilage cells or tumor cells or liver cells.

The current invention relates to a composition for parenteral administration comprising a canine plasma and hyaluronic acid or a salt or ester thereof, wherein said plasma comprises lipids and/or phospholipids. The inventions also relates to a kit comprising one or more aliquots of a composition, said composition comprising a canine plasma comprising lipids and/or phospholipids and hyaluronic acid or a derivative thereof and optionally one or more pharmaceutical active ingredients, wherein said kit further comprises one or more aliquots of a calcium source, preferably a calcium chloride solution. The invention also pertains to the composition and kit of current invention for use in the treatment of musculoskeletal diseases.

The present application is directed to a method of treating osteoarthritis, which includes obtaining a member of a transforming growth factor superfamily of proteins; obtaining a population of cultured mammalian cells that may contain vector encoding a gene, or a population of cultured connective tissue cells that do not contain any vector encoding a gene; and then transferring the protein and the connective tissue cells into an arthritic joint space of a mammalian host, such that the activity of the combination within the joint space results in regenerating connective tissue.

A method for preparing zonal layered chondrocyte sheets, comprising the steps: (a) providing a cartilage sample from a subject; (b) isolating chondrocytes from the cartilage sample and then isolating superficial zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes from the chondrocytes; (c) culturing the deep zone chondrocytes until reaching 100% cell confluence to form a deep zone chondrocyte sheet; (d) seeding the middle zone chondrocytes on the top of the cultured deep zone chondrocyte sheet from the step (c) and culturing the middle zone chondrocytes until reaching 100% cell confluence to form a middle zone chondrocyte sheet; and (e) seeding the superficial zone chondrocytes on the top of the cultured middle zone chondrocyte sheet from the step (d) and culturing the superficial zone chondrocytes until reaching 100% cell confluence to form a superficial zone chondrocyte sheet to obtain the zonal layered chondrocyte sheets.