A method is provided for producing a live cartilaginous material useful for implantation into a patient. A method of treating a patient comprising implanting a cartilaginous material prepared according to the provided method in an anatomical site in a patient also is provided.

The present invention provides a cell culture having a cartilage-like tissue forming property, including a cell population in which the expression intensity of at least one cell surface marker selected from the group consisting of CD166, CD165, CD99, GD2, STRO-1, CD108, CD164, CD6, CD106, and CD107b is not higher than the threshold for each cell surface marker, and/or, the expression intensity of at least one cell surface marker selected from the group consisting of CD26, CD73, CD105, CD44, CD120a, CD201, EGFR, CD146, CD140a, and CD90 is not lower than the threshold for each cell surface marker.

Methods and compositions are provided for the regeneration of articular cartilage by activating skeletal stem cells with a combination of (i) mechanical and (ii) biochemical stimulus. The mechanical stimulus can be an acute local injury. The biochemical stimulus can be a combination of an effective dose of a BMP2 activating agent and a VEGF inhibitor.

A method for in vitro production of cartilage tissue, which includes the steps of: i) culturing chondrocytes on an adherent culture system in a dedifferentiation culture medium that activates Wnt signaling pathway to obtain chondrocytes with a morphology of fibroblastic-like cells; ii) culturing the fibroblastic-like chondrocytes on an adherent culture system in a redifferentiation culture medium that inactivates Wnt signaling pathway to obtain chondrocytes with full capacity to resynthesize hyaline matrix; and iii) culturing the chondrocytes obtained in step ii) in a three-dimensional culture system in induction/maturation culture medium that maintain the inactivation of Wnt signaling pathway. Also, the therapeutic uses and screening methods using the cartilage tissue thus produced.

The present invention relates to biomaterial in the form of dispersion of cellulose nanofibrils with extraordinary shear thinning properties which can be converted into desire 3D shape using 3D Bioprinting technology. In this invention cellulose nanofibril dispersion, is processed through different mechanical, enzymatic and chemical steps to yield dispersion with desired morphological and rheological properties to be used as bioink in 3D Bioprinter. The processes are followed by purification, adjusting of osmolarity of the material and sterilization to yield biomaterial which has cytocompatibility and can be combined with living cells. Cellulose nanofibrils can be produced by microbial process but can also be isolated from plant secondary or primary cell wall, animals such as tunicates, algae and fungi. The present invention describes applications of this novel cellulose nanofibrillar bioink for 3D Bioprinting of tissue and organs with desired architecture.

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.

Disclosed herein is a cross-linked polymeric system comprising thiolated hyaluronic acid (HA), thiolated chondroitin sulfate (CS), and functionalized polyethylene glycol (PEG), wherein said functionalized PEG cross-links thiolated HA and thiolated CS. Methods of fabrication and utilization of the same are also claimed. This polymeric system may be used as an engineered biocompatible cellular matrix for 3D cell culture, tissue engineering and regenerative medicine applications.

The present invention relates to a method of providing a graft scaffold for cartilage repair, particularly in a human patient. The method of the invention comprising the steps of providing particles and/or fibres; providing an aqueous solution of a gelling polysaccharide; providing mammalian cells; mixing said particles and/or fibres, said aqueous solution of a gelling polysaccharide and said mammalian cells to obtain a printing mix; and depositing said printing mix in a three-dimensional form. The invention further relates to graft scaffolds and grafts obtained by the method of the invention.

This disclosure describes bone tissues engineered from a casted bio-nanocomposite comprising chitosan crosslinked with citric acid to cellulose nanocrystals (CNC) where the amount of CNC used was as high as 29.4%. The nanocomposite showed proper characteristics of a bone mimicking structure. Different layers of the bio-nanocomposite showed an average pore size of greater than 26 micrometers in diameter; a porosity of about 90%, firm structure, maximum bioactivity as measured by deposition of calcium phosphate from simulated body fluid (SBF) solution (gaining weight more than 20% after 3 days), decreased rate of in vitro degradation in PBS (7-60 days), about 10% after 7 days, and acceptable bone cell viability (greater than 80%) in 2D and 3D cultures. The compression modulus of the bio-nanocomposites increased about 4 times and exhibited very small changes in size during the swelling process compared to control.

A method of culturing a cell population containing cartilage-derived cells positive for expression of Tie2 (cartilage-derived Tie2-positive cells), the method including culturing a cell population containing cartilage-derived Tie2-positive cells in a culture medium containing at least one kind of Tie2 expression enhancer other than growth factors (e.g., an extract derived from a plant of the genus Cinnamomum). This culturing method is preferably performed in cultureware having a culture surface coated with a coating agent (e.g., a polylysine-containing agent).