Gellan gum-based hydrogels are disclosed herein for in vitro cell culture and tissue engineering and regenerative medicine applications. Such gellan gum-based hydrogels may be used alone or combined with live cells and/or biomolecules for application in humans and/or animals. Chemical modification of gellan gum with selected ion-chelating substituents affords novel gellan gum hydrogels endowed with tunable physicochemical and biological properties. The modified gellan gum hydrogels described herein present advantages over existing hydrogel systems, including solubility, ionic crosslinking versatility, ease of formulation and injectability and greater adhesiveness within biological tissues and surfaces, whilst maintaining encapsulated cells viable during long culture periods and up-regulating the expression of healthy extracellular matrix markers.

The subject invention pertains to a device and methods for inducing tensile strain on a hydrogel and/or hydrogel-encapsulated cells and/or tissues. The device includes a hydrogel-based mold for cell culture and a magnet-combined rail slider for cyclic tensile stretch. The resulting hydrogel-based device provides controllable tensile strain to cells and/tissues, from which cells and/or tissues can be encapsulated in hydrogels and strain can be applied cyclically.

The present application relates to a method of inducing differentiation of stem cells into chondrocytes using an oligopeptide, and a pharmaceutical composition for treating cartilage injury disease containing differentiated chondrocytes obtained by the method.

The present invention is to provide a method for producing a cartilage tissue which comprises a step of providing a substrate for producing cell aggregates provided with a plurality of spots comprising a copolymer containing recurring units derived from monomers represented by the following formulae (I) and (II):

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[wherein U.sup.a1, U.sup.a, R.sup.a1, R.sup.a2 and R.sup.b are as described in the specification and claims] on a substrate having an ability to suppress adhesion of cells; a step of seeding human cartilage progenitor cells which are positive for PRRX1 protein and derived from pluripotent stem cells on the substrate; a step of producing cell aggregates by culturing the cells; and a step of culturing the aggregates to produce a cartilage tissue.

Methods for generating human induced mesenchymal stem cells (iMSC) from human pluripotent stem cells, such as embryonic stem cells, are provided. Progenitors of iMSCs are first generated in a two-step protocol, with further differentiation to iMSCs accomplished by a third step culture. The iMSCs express mesenchymal surface markers and exhibit trilineage differentiation to adipocytes, osteocytes and chondrocytes. Culture media, methods of isolating extracellular vesicles from the iMSCs and kits are also provided.

Methods and compositions for the biological repair of cartilage using a hybrid construct combining both an inert structure and living core are described. The inert structure is intended to act not only as a delivery system to feed and grow a living core component, but also as an inducer of cell differentiation. The inert structure comprises concentric internal and external and inflatable/expandable balloon-like bio-polymers. The living core comprises the cell-matrix construct comprised of HDFs, for example, seeded in a scaffold. The method comprises surgically removing a damaged cartilage from a patient and inserting the hybrid construct into the cavity generated after the foregoing surgical intervention. The balloons of the inert structure are successively inflated within the target area, such as a joint, for example. Also disclosed herein are methods for growing and differentiating human fibroblasts into chondrocyte-like cells via mechanical strain.

The present invention concerns a method for obtaining an implantable cartilage gel for tissue repair of hyaline cartilage, comprising particles of chitosan hydrogel and cells that are capable of forming hyaline cartilage, said method comprising a step for amplification of primary cells in a three-dimensional structure comprising particles of physical hydrogel of chitosan or a chitosan derivative, then a step for re-differentiation and induction of the synthesis of extracellular matrix by said amplified cells, in the same three-dimensional structure, wherein said cells are primary articular chondrocytes and/or mesenchymal stem cells differentiated into chondrocytes. The present invention also concerns the cartilage gel obtained thereby, and its various uses for cartilage repair following a traumatic lesion or an osteoarticular disease such as osteoarthritis. The invention also concerns a three-dimensional matrix comprising particles of physical hydrogel of chitosan or of chitosan derivative, optionally supplemented with an anionic molecule such as hyaluronic acid or a derivative of hyaluronic acid or a complex of hyaluronic acid.

Provide are a porous cell scaffold including a serum-induced protein and a method of manufacturing the same. A porous cell scaffold according to an embodiment may stably and continuously incubate cells, show a culture pattern suitable for the characteristics of each cell to simulate actual tissues, and have a stable culture and high in vivo engraftment rate. Accordingly, the porous cell scaffold can be usefully used in the evaluation of drug activity and toxicity using organoids, for use in cell therapy products, or in the production of a target protein.

Engineered neocartilage tissue compositions comprising human rib cartilage-derived cells at passage 5 (P5) or greater and methods for producing said engineered neocartilage tissue compositions. The engineered neocartilage tissue compositions are scaffold-free and feature the use of highly expanded cells exhibiting functional properties similar to native articular cartilage. The human rib cartilage-derived cells may be allogeneic cells. The tissue compositions herein may be configured for surgical implantation. The tissue compositions may be configured to repair a variety of tissues and defects such as, but not limited to, hyaline cartilage, fibrocartilage, elastic cartilage, chondral lesions, osteochondral lesions, osteoarthritic conditions, a temporomandibular joint (TMJ) disc complex, TMJ tissues, a knee meniscus, nasal cartilages, facet cartilages, knee articular cartilage, ear cartilage, or a combination thereof.

Methods and systems for enhancing cell populations such as chondrocytes for tissue engineering applications, e.g., for production of neocartilage. The methods and systems of the present invention feature the introduction of a hypotonic buffer to the cells during the cell isolation process, which results in neotissue (e.g., neocartilage) constructs that are significantly more mechanically robust as compared to those not treated with hypotonic buffer. The methods and systems may further comprise introducing cytochalasin D to cells purified with a hypotonic buffer, which can further bolster the mechanical properties and matrix deposition of the cells. The methods and systems result in neocartilage engineered from chondrocytes, for example, from fetal aged tissue, having compressive properties on par with native adult articular cartilage.