3D in vitro bi-phasic cartilage-bone construct

Inventors

Rosowski, MarkKadler, ShirinLauster, RolandMarx, Uwe

Assignees

TISSUSE GmbH

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Publication Number

US-9856458-B2

Patent

Publication Date

2018-01-02

Expiration Date


Abstract

A 3D in vitro bi-phasic cartilage-bone organoid includes a layer of an artificial cartilage tissue, and a layer of an artificial bone tissue comprising a structure-giving scaffold and a bone marrow structure. The layer of the artificial cartilage tissue contacts at least one surface of the layer of the artificial bone tissue.

Core Innovation

The invention provides a three dimensional in vitro bi-phasic cartilage-bone organoid comprising a layer of an artificial cartilage tissue and a layer of an artificial bone tissue comprising a structure-giving scaffold and a bone marrow structure. The artificial cartilage tissue layer contacts at least one surface of the artificial bone tissue layer, thereby forming a biphasic cartilage-bone arrangement in vitro.

In the artificial bone tissue layer, the structure-giving scaffold comprises a 3D zirconium oxide based, hydroxyapatite coated ceramic. The bone marrow structure of the artificial bone tissue comprises mesenchymal stem cells and hematopoietic stem cells, defining a scaffolded bone compartment together with a mesenchymal/hematopoietic stem cell-containing bone marrow structure.

The artificial cartilage tissue is prepared by providing mesenchymal progenitor cells and culturing the mesenchymal progenitor cells under non-adherent conditions so as to form chondrogenic cell aggregates as the artificial cartilage tissue. The biphasic organoid combines a non-adherent, chondrogenic aggregate-based cartilage layer with a scaffolded, stem-cell-containing bone marrow layer that is in contact at the tissue interface.

Claims Coverage

The independent claim covers a 3D in vitro bi-phasic cartilage-bone organoid with four core inventive aspects: (i) a contacting artificial cartilage layer and artificial bone layer; (ii) a 3D zirconium oxide based, hydroxyapatite coated ceramic scaffold; (iii) a bone marrow structure comprising mesenchymal stem cells and hematopoietic stem cells; and (iv) artificial cartilage tissue formed from mesenchymal progenitor cells under non-adherent conditions to form chondrogenic cell aggregates.

Contacting artificial cartilage and artificial bone layers

The layer of the artificial cartilage tissue contacts at least one surface of the layer of the artificial bone tissue.

Zirconium oxide based hydroxyapatite coated ceramic bone scaffold

The structure-giving scaffold of the artificial bone tissue comprises a 3D zirconium oxide based, hydroxyapatite coated ceramic.

Bone marrow structure with mesenchymal stem cells and hematopoietic stem cells

The bone marrow structure of the artificial bone tissue comprises mesenchymal stem cells and hematopoietic stem cells prepared by seeding mesenchymal stem cells on the structure-giving scaffold, culturing the mesenchymal stem cell on the structure-giving scaffold, and adding the hematopoietic stem cells.

Chondrogenic aggregates from non-adherent mesenchymal progenitors

The artificial cartilage tissue is prepared by providing mesenchymal progenitor cells and culturing the mesenchymal progenitor cells under non-adherent conditions so as to form chondrogenic cell aggregates as the artificial cartilage tissue.

Overall, the claim coverage centers on a 3D in vitro biphasic cartilage-bone organoid that integrates a non-adherent, chondrogenic-aggregate cartilage layer with a zirconium oxide/hydroxyapatite ceramic scaffold-based bone layer containing mesenchymal stem cells and hematopoietic stem cells, arranged so that the cartilage layer contacts at least one surface of the bone layer.

Stated Advantages

Documented Applications

No documented applications found

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